Synthesis and applications of cyclopeptides and depsipeptides

A solid phase protocol has been devised for the synthesis of linearprecursors to cyclic depsipeptide analogues of dolastatin D.t-Butyldimethylsilyl groups were used for hydroxy group protection, withdeprotection being carried out by t-butyl ammonium fluoride. HATU and PyBropwere successful in coupling highly hindered residues and in depside bondformation. Cyclic peptide analogues, cyclo[Arg-Gly-Asp-d-Phe-Lys(or Tyr)]have been synthesised and modified for use as carrier molecules for thetransport of radio isotopes (¹¹¹In and ¹²⁵I)into blood platelets as prototypes for medical imaging.     

Tables and Procedures for the Determination of Power and Sample Sizes in Univariate and Multivariate Analyses of Variance and Regression

The available power tables for use in experimental design only serve for limited practical purposes, since they are restricted to very few levels of significance such as .01, .05, and .10. With these values, however, usually no correction for cumulating error probabilities, for example, by the Dunn-Bonferroni method, can be achieved, because (very) low values of a and sometimes even of α are necessary. Therefore, power tables are presented that encompass a wide range of different values for a (.0005 to .40), for power (.50 to .9995), and for 45 different values of the degrees of freedom for the numerator of the F ratio (u = 1 to 150). Four of the 16 tables are printed. Their use is demonstrated for some paradigmatic problems in univariate and multivariate analyses of variance and regression.     

Biokinetic and toxicodynamic modelling and its role in toxicological research and risk assessment

Toxicological risk assessment for chemicals is still mainly based on highly standardised protocols for animal experimentation and exposure assessment. However, developments in our knowledge of general physiology, in chemicobiological interactions and in (computer-supported) modelling, have resulted in a tremendous change in our understanding of the molecular mechanisms underlying the toxicity of chemicals. This permits the development of biologically based models, in which the biokinetics as well as the toxicodynamics of compounds can be described. In this paper, the possibilities are discussed of developing systems in which the systemic (acute and chronic) toxicities of chemicals can be quantified without the heavy reliance on animal experiments. By integrating data derived from different sources, predictions of toxicity can be made. Key elements in this integrated approach are the evaluation of chemical functionalities representing structural alerts for toxic actions, the construction of biokinetic models on the basis of non-animal data (for example, tissue-blood partition coefficients, in vitro biotransformation parameters), tests or batteries of tests for determining basal cytotoxicity, and more-specific tests for evaluating tissue or organ toxicity. It is concluded that this approach is a useful tool for various steps in toxicological hazard and risk assessment, especially for those forms of toxicity for which validated in vitro and other non-animal tests have already been developed.     

生物多样性与生态系统服务——关系、权衡与管理

生物多样性和生态系统服务是人类生存和社会经济可持续发展的物质基础,应对生物多样性丧失和生态系统服务退化问题已经成为继气候变化之后的又一个全球性环境热点问题。生物多样性是生态系统生产力、稳定性、抵抗生物入侵以及养分动态的主要决定因素,生物多样性越高,生态系统功能性状的范围越广,生态系统服务质量就越高越稳定。目的是探讨生物多样性和生态系统服务之间的关系:(1)明确了生物多样性与生态系统过程、功能、服务之间的关系;(2)生物多样性在生态系统服务中的角色:生物多样性在不同的空间尺度通过各种形式的运行机制与生态系统服务产生联系,生物多样性是生态系统过程的调节者,是巩固生态系统服务的一个重要因素,生物多样性也是一种终极的生态系统服务,并在遗传和物种水平上直接贡献了其利益和价值;(3)生物多样性与生态系统服务权衡和协同关系的研究可以更好的帮助管理人员做出有利的决策和保护工作,也是制定规划和适应策略以减少生物多样性危机带来的不利影响的基础;(4)生物多样性与生态系统服务的关系在不同的时间和空间尺度上是不恒定的,有必要共同确定生态系统服务和生物多样性的空间格局,以有效和可持续的进行生态系统管理;(5)虽然生物多样性保护和生态系统管理还存在许多不确定性,但相关理论应该在管理、保护和恢复生态系统中发挥重要作用。研究提出了进一步研究的领域,以促进生物多样性保护和生态系统服务提供之间的协同作用。希望对相关领域的研究有所帮助。     

Polyphenols and health: Update and perspectives

Current issues in research on health effects by polyphenols are addressed. As to the cardiovascular system, flow-mediated dilation (FMD), a functional biomarker, can be used as surrogate marker for cardiovascular risk. Acute short-term effects peaking at 2 h after ingestion of polyphenol-rich food items are distinguished from longer-term effects over days and weeks. The role of polyphenol metabolites as bioactives is presented, underlining that specific target enzymes such as NADPH oxidases or lipoxygenases provide a basis for molecular action of polyphenols, rather than unspecific direct antioxidant effects. Cautionary words are given for the use of non-compositional assays of ‘total antioxidant capacity’ (TAC) in blood plasma. Enhanced interest emerges for polyphenols in the gastrointestinal tract. Recommendations for health professionals and the public are summarized, as well as prospects and challenges for future research.     

Prenatal ages and stages-measures and errors

BACKGROUND: The confusing term "gestational age" is generally either not defined or is used for menstrual "age," postovulatory age, or postfertilizational age. The designation (post)menstrual weeks and/or days is very useful in obstetrics but, because prenatal age extends from fertilization to birth, menstrual "age" is a misnomer. The term "stage" has a specific morphological meaning in embryology and should not be used either for ages or for lengths. METHODS: Embryonic age is best assessed, when possible, from the 23 internationally recognized morphological stages. A morphological staging system is not available for the fetal period, and fetal age is assessed mainly from measurements. RESULTS: Among these, the unsatisfactory designation crown-rump length (CRL) should be replaced, in ultrasonic biometry as well as in embryology, by the greatest length (GL), exclusive of the lower limbs. These points are discussed in detail, and justification for the views expressed is provided. CONCLUSIONS: The continuing confusion concerning prenatal age is shown to be unnecessary once the ambiguous and superfluous term "gestational age" is abandoned.     

Synthesis and applications of cyclopeptides and depsipeptides

Summary A solid phase protocol has been devised for the synthesis of linear precursors to cyclic depsipeptide analogues of dolastatin D.t-Butyldimethylsilyl groups were used for hydroxy group protection, with deprotection being carried out byt-butyl ammonium fluoride. HATU and PyBrop were successful in coupling highly hindered residues and in depside bond formation. Cyclic peptide analogues, cyclo[Arg-Gly-Asp-d-Phe-Lys(or Tyr)] have been synthesised and modified for use as carrier molecules for the transport of radio isotopes (¹¹¹In and¹²⁵I) into blood platelets as prototypes for medical imaging.     

Health and Welfare in Animals and Humans

This paper contains a brief comparative analysis of some philosophical and scientific discourses on human and animal health and welfare, focusing mainly on the welfare of sentient animals. The paper sets forth two kinds of proposals for the analysis of animal welfare which do not appear in the contemporary philosophical discussion of human welfare, viz. the coping theory of welfare and the theory of welfare in terms of natural behaviour. These proposals are scrutinized in the light of some similar theories dealing with human health and quality of life. My conclusion is that the coping theory and the natural behaviour theory are not in themselves adequate for the characterization of welfare, either for humans or for sentient animals. I contend, finally, that, in the light of the previous discussion, there are good arguments for a particular set of analyses of both animal and human welfare, viz. the ones that are based on the notions of preference satisfaction and positive subjective experiences.     

Models and estimators linking individual-based and sample-based rarefaction,extrapolation and comparison of assemblages

Aims In ecology and conservation biology, the number of species counted in a biodiversity study is a key metric but is usually a biased underestimate of total species richness because many rare species are not detected. Moreover, comparing species richness among sites or samples is a statistical challenge because the observed number of species is sensitive to the number of individuals counted or the area sampled. For individual-based data, we treat a single, empirical sample of species abundances from an investigator-defined species assemblage or community as a reference point for two estimation objectives under two sampling models: estimating the expected number of species (and its unconditional variance) in a random sample of (i) a smaller number of individuals (multinomial model) or a smaller area sampled (Poisson model) and (ii) a larger number of individuals or a larger area sampled. For sample-based incidence (presence–absence) data, under a Bernoulli product model, we treat a single set of species incidence frequencies as the reference point to estimate richness for smaller and larger numbers of sampling units.Methods The first objective is a problem in interpolation that we address with classical rarefaction (multinomial model) and Coleman rarefaction (Poisson model) for individual-based data and with sample-based rarefaction (Bernoulli product model) for incidence frequencies. The second is a problem in extrapolation that we address with sampling-theoretic predictors for the number of species in a larger sample (multinomial model), a larger area (Poisson model) or a larger number of sampling units (Bernoulli product model), based on an estimate of asymptotic species richness. Although published methods exist for many of these objectives, we bring them together here with some new estimators under a unified statistical and notational framework. This novel integration of mathematically distinct approaches allowed us to link interpolated (rarefaction) curves and extrapolated curves to plot a unified species accumulation curve for empirical examples. We provide new, unconditional variance estimators for classical, individual-based rarefaction and for Coleman rarefaction, long missing from the toolkit of biodiversity measurement. We illustrate these methods with datasets for tropical beetles, tropical trees and tropical ants.Important findings Surprisingly, for all datasets we examined, the interpolation (rarefaction) curve and the extrapolation curve meet smoothly at the reference sample, yielding a single curve. Moreover, curves representing 95% confidence intervals for interpolated and extrapolated richness estimates also meet smoothly, allowing rigorous statistical comparison of samples not only for rarefaction but also for extrapolated richness values. The confidence intervals widen as the extrapolation moves further beyond the reference sample, but the method gives reasonable results for extrapolations up to about double or triple the original abundance or area of the reference sample. We found that the multinomial and Poisson models produced indistinguishable results, in units of estimated species, for all estimators and datasets. For sample-based abundance data, which allows the comparison of all three models, the Bernoulli product model generally yields lower richness estimates for rarefied data than either the multinomial or the Poisson models because of the ubiquity of non-random spatial distributions in nature.     

Features and applications of blue-native and clear-native electrophoresis

1-D native electrophoresis is used for the separation of individual proteins, protein complexes, and supercomplexes. Stable and labile protein-protein interactions can be identified depending on detergent and buffer conditions. 1-D native gels are immediately applicable for in-gel detection of fluorescent-labeled proteins and for in-gel catalytic activity assays. 1-D native gels and blots are used to determine native mass and oligomeric state of membrane proteins. Protein extracts from 1-D native gels are used for generation of antibodies, for proteomic work, and for advanced structural investigations. 2-D separation of subunits of protein complexes by SDS-PAGE is mostly used for immunological and proteomic studies. Following the discussion of these general features, specific applications of native electrophoresis techniques in various research fields are highlighted: immunological and receptor studies, biogenesis and assembly of membrane protein complexes, protein import into organelles, dynamics of proteasomes, proteome and subproteome investigations, the identification and quantification of mitochondrial alterations in apoptosis, carcinogenesis, and neurodegenerative disorders like Parkinson's disease, Alzheimer's disease, and the vast variety of mitochondrial encephalomyopathies.     

Opuntia and Other Cacti: Applications and Biotechnological Insights

The cactus family is unusual among tropical plants. Cacti, known for their minimum water requirement, have been grown extensively in arid lands, for food, feeds and medicinal and therapeutic uses.Several food products have cacti as a main ingredient. Cacti biochemical analysis substantiate the high nutritive value of this plant family. Tissue cultures, including micropropagation, callus, and cell suspension cultures have been established for numerous cacti species. Genetic engineering has opened opportunities for gene isolation and integration of genes from other sources for cacti improvement. Cacti might be a store house of stress tolerant genes for other crops. Since cacti can be cultivated easily with minimum agriculture inputs, they hold great potential for cultivation and farming on degraded lands and for at least partial remediation of degraded lands. The present review outlines some of the older and more recent research on the properties and applications for Opuntia and other cacti especially as they might apply towards agricultural sustainability.     

Measurement of phenol and p-cresol in urine and feces using vacuum microdistillation and high-performance liquid chromatography

In this article, we describe a simple, sensitive, accurate, and repeatable method for the measurement of phenol and p-cresol (4-methylphenol) in human urine and feces. We examined a number of parameters to identify an optimal extraction protocol. Purification of sample extracts was achieved by low-temperature vacuum microdistillation. Separation was achieved in approximately 15 min by high-performance liquid chromatography (HPLC) with quantification by fluorescence at 284/310 nm. Limits of detection for phenol were 2 ng/ml for urine and 20 ng/g for feces, and those for p-cresol were 10 ng/ml for urine and 100 ng/g for feces. For comparison, approximate mean values for urine are 3 μg/ml for phenol and 30 μg/ml for p-cresol, and those for feces are 1 μg/g for phenol and 50 μg/g for p-cresol. An experienced analyst can process 60 samples each day using this method.     

Muscle strength and myoelectric activity in prepubertal and adult males and females

The purpose of this investigation was to compare children and adults of both genders with respect to torque-velocity, electromyogram (EMG)-velocity and torque-EMG relationships during maximal voluntary knee extensor muscle actions. Four groups of ten subjects each were studied comprising 11-year-old girls and boys and female and male physical education students (22–35 years). Maximal voluntary eccentric (lengthening) and concentric (shortening) actions of the knee extensors were performed at the constant velocities of 45, 90 and 180° · s^–1. Average values for torque and EMG activity, recorded by surface electrodes from the quadriceps muscle, were taken for the mid 40° of the 80° range of motion. The overall shapes of the torque- and EMG-velocity relationships were similar for all four groups, showing effects of velocity under concentric (torque decrease and EMG increase) but not under eccentric conditions. Eccentric torques were always greater than velocity-matched concentric ones, whereas the eccentric EMG values were lower than the concentric ones at corresponding velocities. Torque output per unit EMG activity was clearly higher for eccentric than for concentric conditions and the difference was of similar magnitude for all groups. Thus, the torque-EMG-velocity relationships would appear to have been largely independent of gender and to be fully developed at a prepubertal age.     

Availability and Readability of Emergency Preparedness Materials for Deaf and Hard-of-Hearing and Older Adult Populations: Issues and Assessments

A major public health challenge is to communicate effectively with vulnerable populations about preparing for disasters and other health emergencies. People who are Deaf or Hard of Hearing (Deaf/HH) and older adults are particularly vulnerable during health emergencies and require communications that are accessible and understandable. Although health literacy studies indicate that the readability of health communication materials often exceeds people’s literacy levels, we could find no research about the readability of emergency preparedness materials (EPM) intended for Deaf/HH and older adult populations. The objective of this study was to explore issues related to EPM for Deaf/HH and older adult populations, to assess the availability and readability of materials for these populations, and to recommend improvements. In two California counties, we interviewed staff at 14 community-based organizations (CBOs) serving Deaf/HH clients and 20 CBOs serving older adults selected from a stratified, random sample of 227 CBOs. We collected 40 EPM from 10 CBOs and 2 public health departments and 40 EPM from 14 local and national websites with EPM for the public. We used computerized assessments to test the U.S. grade reading levels of the 16 eligible CBO and health department EPM, and the 18 eligible website materials. Results showed that less than half of CBOs had EPM for their clients. All EPM intended for clients of Deaf/HH-serving CBOs tested above the recommended 4^th grade reading level, and 91% of the materials intended for clients of older adult-serving CBOs scored above the recommended 6^th grade level. EPM for these populations should be widely available through CBOs and public health departments, adhere to health literacy principles, and be accessible in alternative formats including American Sign Language. Developers should engage the intended users of EPM as co-designers and testers. This study adds to the limited literature about EPM for these populations.     

Local and Systemic Antibiotic Therapy of Wounds and Burns

Postoperative wound infection rates range between 3% for clean wounds to 28% for dirty wounds. Indiscriminate antibiotic prophylaxis is ineffective. Requisites for effectiveness are specificity of the antibiotic for wound pathogens, the achievement of therapeutic tissue levels within four to six hours of wounding, and use only for high-risk situations. Topical neomycin is recommended in special-risk clean cases. In addition, in contaminated cases, a combination of penicillin G, a biosynthetic penicillin, and broad-spectrum penicillin parenterally is used, preoperatively, intra-operatively, and immediately postoperatively. Intravenous penicillin G and a biosynthetic penicillin are used for patients with major trauma and burns.     

Effects of osmotic priming and ageing on the germination and emergence of carrot and leek seed

Carrot and leek seed was osmotically primed in polyethylene glycol solution (273 g/kg water and 342 g/kg water respectively) for 10, 14 or 17 days before accelerated ageing for 0, 24, 48, 72 or 96 h. Priming reduced the germination time compared with non-primed seed. Accelerated ageing increased germination and emergence times and decreased percentage germination and emergence to a greater extent for the primed seeds than for non-primed seeds in both species. Primed and dried but non-aged seed from both species was stored at 10°C for 12 months. There was no loss of viability and improvements in germination time due to priming were maintained throughout the storage period for all the priming treatments in leek, and for the 10 and 14 day priming treatments in carrot. Carrot seed primed for 17 days lost some viability after 12 months storage compared with non-stored seed.     

Glutamine and glutamate--their central role in cell metabolism and function

Glucose is widely accepted as the primary nutrient for maintenance and promotion of cell function. However, we propose that the 5-carbon amino acids, glutamine and glutamate, should be considered to be equally important for maintenance and promotion of cell function. The functions of glutamine are many and include: substrate for protein synthesis, anabolic precursor for muscle growth, acid-base balance in the kidney, substrate for ureogenesis in the liver, substrate for hepatic and renal gluconeogenesis, an oxidative fuel for intestine and cells of the immune system, inter-organ nitrogen transport, precursor for neurotransmitter synthesis, precursor for nucleotide and nucleic acid synthesis and precursor for glutathione production. Many of these functions are connected to the formation of glutamate from glutamine. We propose that the unique properties regarding concentration and routes of metabolism of these amino acids allow them to be used for a diverse array of processes related to the specialized function of each of the glutamine utilizing cells. In this review we highlight the specialized aspects of glutamine/glutamate metabolism of different glutamine-utilizing cells and in each case relate key aspects of metabolism to cell function.     

Azaperone and azaperone-ketamine as a neuroleptic sedative and anesthetic in rats and mice

Azaperone alone and combined with ketamine were evaluated as sedative and anesthetic agents in outbred rats and mice. Using azaperone alone the duration of immobility was 1.9 to 10.8 hours for mice and 0.9 to 2.4 hours for rats. The withdrawal reflex was not eliminated from mice receiving azaperone alone; however, the withdrawal reflex was eliminated from 0.9 to 2.4 hours in rats receiving azaperone. Azaperone produced a tachypnea in rats and male mice while a depressed respiratory rate was observed in female mice. Using azaperone combined with ketamine, the duration of immobilization was 1.1 to 8.8 hours for mice and 1.3 to 6.0 hours for rats. The duration loss of the withdrawal reflex, which was used as an indication of surgical anesthesia, was 0.9 to 1.8 hours for mice and 1.0 to 6.0 hours for rats. An increase in respiratory rate was observed in rats given the combination while mice given the combination showed transient tachypnea followed by bradypnea. Overall, azaperone alone was shown to provide sedation in mice as compared to a dose dependent anesthesia in rats. The azaperone-ketamine combination produced a surgical plane of anesthesia in both rats and mice. Azaperone and the azaperone-ketamine combination appear to be a suitable alternative to sedatives and anesthetics currently used in rats and mice.     

Synthesis and turnover of cerebrosides and phosphatidylserine of myelin and microsomal fractions of adult and developing rat brain.

The synthesis and turnover of cerebrosides and phospholipids was followed in microsomal and myelin fractions of developing and adult rat brains after an intracerebral injection of [U-14C]serine. The kinetics of incorporation of radioactivity into microsomal and myelin cerebrosides indicate the possibility of a precursor-product relationship between cerebrosides of these membranes. The specific radioactivity of myelin cerebrosides was corrected for the deposition of newly formed cerebrosides in myelin. Multiphasic curves were obtained for the decline in specific radioactivity of myelin and microsomal cerebrosides, suggesting different cerebroside pools in these membranes. The half-life of the fast turning-over pool of cerebrosides of myelin was 7 and 22 days for the developing and adult rat brain respectively. The half-life of the slowly turning-over pool of myelin cerebrosides was about 145 days for both groups of animals. The half-life of the rapidly turning-over microsomal cerebrosides was calculated to be 20 and 40 h for the developing and adult animals respectively. The half-life of the intermediate and slowly turning-over microsomal cerebrosides was 11 and 60 days respectively, for both groups of animals. The amount of incorporation of radioactivity into microsomal cerebrosides from L-serine was greatly decreased in the adult animals, and greater amounts of the precursor were directed towards the synthesis of phosphatidylserine. In the developing animals, considerable amounts of cerebrosides were synthesized from L-serine, besides phosphatidylserine. The time-course of incorporation indicated that a precursor-product relationship exists between microsomal and myelin phosphatidylserine. The half-life of microsomal phosphatidylserine was calculated to be about 8 h for the fast turning-over pool in both groups of animals.