Phenylalanine metabolites as indicators of dietary compliance in children with phenylketonuria

The data from this study showed that the excretion of three major metabolites of phenylalanine in patients with PKU approach normal values at blood phenylalanine levels less than 5.0 mg/dl. The MANOVA showed statistically significant differences in phenyllactate excretion when blood phenylalanine was greater than 10.0 mg/dl. The PL and total metabolite excretion were significantly correlated to blood phenylalanine in multiple samples taken from two individual subjects. Using data obtained from single patient observations may serve as a means for individualizing the PKU diet to insure low levels of phenylalanine metabolites and thus insure optimal development for patients with PKU.     

动物病理学在新药开发风险控制中的作用

目的 进行临床前研究的主要原因在于,保证研究中新药探索实验中尤其是研发早期试验人群的安全,因为只是减少健康志愿者身上的风险无益于保证（所有）受试者的安全.内容 本文从新药研发的两个阶段分别对病理学在临床前风险控制研究中的作用进行了讨论.结论 在非临床前新药研发阶段的风险控制中,让病理学家参与到新药研发的风险管理队伍中来,帮助研发、监控研发,是成功研发与优良的风险管理策略相衔接的关键.     

Assaying the DNA damage checkpoint in fission yeast

Cell cycle checkpoints exist to ensure the proper maintenance and stable inheritance of genomic information. The pathways that insure the faithful execution of these checkpoints are well conserved throughout evolution. In the fission yeast, Schizosaccharomyces pombe, a major cell cycle checkpoint exists that responds to the presence of damaged DNA and prevents this damage from being propagated to future generations. Fission yeast is an ideal system to investigate these pathways because there exist specific techniques that allow one to assay the fidelity of this DNA damage checkpoint pathway.     

The Balloon Analog Insurance Task (BAIT): a behavioral measure of protective risk management

Prior methods used to assess individual differences related to risk have not focused on an important component of risk management: how willing individuals are to pay for or take actions to insure what they already have. It is not clear whether this type of protective risk management taps into the same individual differences as does risk taking propensity measured by existing risk taking tasks. We developed a novel task to assess protective risk management, the Balloon Analog Insurance Task (BAIT), which is modeled after the Balloon Analog Risk Task (BART). In the BAIT, individuals are forced to decide how much money they are willing to pay in order to insure a specific fraction of their prior winnings given changing but imprecise levels of risk of monetary loss. Participants completed the BART and BAIT for real monetary rewards, and completed six self report questionnaires. The amount of insurance purchased on the BAIT was positively correlated with scores on the Intolerance of Uncertainty Scale and on the Checking scale of the revised Obsessive Compulsive Inventory. Conversely, the amount of insurance purchased was negatively correlated with scores on the Domain Specific Risk Taking Questionnaire, and on the Psychopathic Personality Inventory (PPI). Furthermore, relationships between insurance purchased and these scales remained significant after controlling for the BART in linear regression analyses, and the BART was only a significant predictor for measures on one scale--the PPI. Our results reveal that behavior on the BAIT taps into a number of individual differences that are not related to behavior on another measure of risk taking. We propose that the BAIT may provide a useful complement to the BART in the assessment of risk management style.     

Developing drugs for the developing world: an economic,legal, moral,and political dilemma

This paper discusses the economic, legal, moral, and political difficulties in developing drugs for the developing world. It argues that large, global pharmaceutical companies have social responsibilities to the developing world, and that they may exercise these responsibilities by investing in research and development related to diseases that affect developing nations, offering discounts on drug prices, and initiating drug giveaways. However, these social responsibilities are not absolute requirements and may be balanced against other obligations and commitments in light of economic, social, legal, political, and other conditions. How a company decides to exercise its social responsibilities to the developing world depends on (1) the prospects for a reasonable profit and (2) the prospects for a productive business environment. Developing nations can either help or hinder the pharmaceutical industry's efforts to exercise social responsibility through various policies and practices. To insure that companies can make a reasonable profit, developing nations should honor pharmaceutical product patents and adhere to international intellectual property treaties, such as the Trade-Related Aspects of Intellectual Property Rights (TRIPS) agreement. To insure the companies have a good business environment, developing nations should try to promote the rule of law, ethical business practices, stable currencies, reliable banking systems, free and open markets, democracy, and other conditions conducive to business. Overall, this paper advocates for reciprocity and cooperation between pharmaceutical companies and developing nations to address the problem of developing drugs for the developing world. In pursuing this cooperative approach, developing nations may use a variety of other techniques to encourage pharmaceutical companies to act responsibly, such as subsidizing pharmaceutical research, helping to design and implement research protocols, providing a guaranteed market, and bulk buying.     

Extreme sequential polyandry insures against nest failure in a frog

Sequential polyandry may evolve as an insurance mechanism to reduce the risk of choosing a mate that is infertile, closely related, genetically inferior or incompatible, but polyandry also might insure against nest failure in unpredictable environments. Most animals are oviparous, and in species where males provide nest sites whose quality varies substantially and unpredictably, polyandrous females might insure offspring success by distributing their eggs across multiple nests. Here, we test this hypothesis in a wild population of an Australian terrestrial toadlet, a polyandrous species, where males construct nests and remain with broods. We found that females partitioned their eggs across the nests of two to eight males and that more polyandrous females gained a significant increase in mean offspring survivorship. Our results provide evidence for the most extreme case of sequential polyandry yet discovered in a vertebrate and also suggest that insurance against nest failure might favour the evolution of polyandry. We propose that insurance against nest failure might be widespread among oviparous taxa and provide an important explanation for the prevalence of sequential polyandry in nature.     

Coordinating Multi-Protein Mismatch Repair by Managing Diffusion Mechanics on the DNA

DNA mismatch repair (MMR) corrects DNA base-pairing errors that occur during DNA replication. MMR catalyzes strand-specific DNA degradation and resynthesis by dynamic molecular coordination of sequential downstream pathways. The temporal and mechanistic order of molecular events is essential to insure interactions in MMR that occur over long distances on the DNA. Biophysical real-time studies of highly conserved components on mismatched DNA have shed light on the mechanics of MMR. Single-molecule imaging has visualized stochastically coordinated MMR interactions that are based on thermal fluctuation-driven motions. In this review, we describe the role of diffusivity and stochasticity in MMR beginning with mismatch recognition through strand-specific excision. We conclude with a perspective of the possible research directions that should solve the remaining questions in MMR.     

Infected Surface Wound: an Experimental Model and a Method for the Quantitation of Bacteria in Infected Tissues

Methods for the quantitation of bacteria in infected tissues must be rigidly standardized to insure uniformity of results. In this communication we report on a laboratory animal model for the study of surface wound infection and the development of a standardized method for the quantitative estimation of bacteria in infected surface wound tissue by mechanical tissue homogenization and serial dilution. Parallel comparative studies demonstrated that a moist-swab sampling procedure detected only 10% of the bacteria recoverable by a surface-wash procedure. Either tissue homogenization or surface-wash procedures recovered significantly more bacteria from contaminated surface wounds than were obtained by surface-swab sampling techniques.     

Nature-inspired Novel Drug Design Paradigm Using Nanosilver: Efficacy on Multi-Drug-Resistant Clinical Isolates of Tuberculosis

Despite discovery of the pathogen more than 100 years ago, tuberculosis (TB) continues to be a major killer disease worldwide. Currently a third of world population is infected and multiple-drug-resistant (mdr) TB registers maximum mortality by a single pathogen. Nanomedicine provides enormous opportunity for developing novel drugs. We have recently demonstrated surface-modified-lipophilic-nanosilica as drug to combat malaria and 100% lethal virus, BmNPV. Nanosilver possesses inherent antibacterial properties, but toxicity is a major concern. We hypothesized that capping with nature-inspired biomolecules, bovine serum albumin (BSA) and Poly-n-vinyl-pyrrolidone (PVP) used as blood volume extender, might insure biosafety. BSA-nano-Ag was found to be more stable than PVP-nano-Ag at physiological pH. In this first ever study on clinical isolates collected from TB endemic areas, we report, BSA-nano-Ag act as potent anti-TB drug. Further study with (human serum albumin)-nano-Ag and core-shell-nano-Ag could increase the biocompatibility of oral TB drug formulations without compromising on the efficacy of the drug.     

叠氮化钠诱变玉扇愈伤组织的研究

在含不同浓度叠氮化钠（0、0.01、0.05、0.1、0.5和1.0mmol·L~（-1））的诱导培养基上诱导玉扇愈伤组织发生变异。结果表明,叠氮化钠对玉扇愈伤组织的半致死浓度为0.1～0.5 mmo1·L~（-1）,0.1 mmol·L~（-1）有利于保证一定量的有效变异率和再生率。再生芽多发生叶片失绿、畸形和叶序改变,其中较多的叶序变异,有望为研究叶序决定提供材料。     

Diel changes in the biochemical composition of the particulate matter coupled with several parameters in the hypereutrophic Villerest reservoir (Roanne,France)

The diel changes of the biochemical composition of particulate matter was studied in Villerest reservoir (located on the Loire river, near the city of Roanne, France) during July 92. Several biomass and metabolic indicators (proteins, carbohydrates, lipids, chlorophyll a and primary production) were assessed bihourly over 2 days.Since the P/C is largely recognized as a good integrator of the metabolic functions of the cells, we examined its distribution pattern concomitantly with aforementioned parameters. The results demonstrated enhanced P/C ratios clearly indicating that nutrients were sufficiently available for growth. In addition, this index showed a diel significant variation with levels higher in the night than in the day. Moreover, these results suggest that phytoplankton species during the night used the day-synthesized carbohydrates to insure the cell metabolic functioning.     

DESIGNING EXPERIMENTS TO MAXIMIZE THE POWER OF DETECTING CORRELATIONS

Studies investigating correlations among traits are increasingly common in evolutionary biology. By providing power calculations, minimum sample sizes, and standard errors of correlation coefficients in a variety of contexts, this note provides guidelines to insure that nonzero correlations will not be erroneously dismissed as nonsignificant in properly designed experiements. Forty individuals is often sufficient for reasonable estimation of correlation coefficients, although 100 or more individuals may be nexessary if a large number of traits are involved or comparisons are to be made among the coefficients.     

Infection by Wolbachia: from passengers to residents

Wolbachia are endosymbiotic alpha-proteobacteria harboured by terrestrial arthropods and filarial nematodes, where they are maternally transmitted through egg cytoplasm. According to the host group, Wolbachia have developed two contrasting symbiotic strategies. In arthropods, symbiosis is secondary (i.e. facultative), and Wolbachia insure their transmission as reproduction parasites. However, despite of the efficiency of the manipulation mechanisms used, Wolbachia are limited to the state of passenger because some factors can prevent the association between Wolbachia and their hosts to become permanent. On the contrary, symbiosis is primary (i.e. obligatory) in filarial nematodes where Wolbachia insure their transmission via a mutualistic relationship, leading them to become permanent residents of their hosts. However, a few examples show that in arthropods too some Wolbachia have started to present the first stages of a mutualistic behaviour, or are even truly indispensable to their host. Whatever its strategy, Wolbachia infection is a spectacular evolutionary success, this symbiotic bacterium representing one of the most important biomass of its kind. To cite this article: H. Merçot, D. Poinsot, C. R. Biologies 332 (2009).     

Transient stress and stress enzyme responses have practical impacts on parameters of embryo development, from IVF to directed differentiation of stem cells

In this review, we discuss the expression, regulation, downstream mechanisms, and function of stress-induced stress enzymes in mammalian oocytes, peri-implantation embryos, and the stem cells derived from those embryos. Recent reports suggest that stress enzymes mediate developmental functions during early mammalian development, in addition to the homeostatic functions shared with somatic cells. Stress-induced enzymes appear to insure that necessary developmental events occur: many of these events may occur at a slower rate, although some may occur more rapidly. Developmental events induced by stress may be mediated by a single dominant enzyme, but there are examples of responses that require the integration of more than one stress enzyme. The discussion focuses on the consequences of stress as a function of duration and magnitude, and this includes an emerging understanding of the threshold levels of duration and magnitude that lead to pathology. Other topics discussed are the reversibility of the developmental as well as homeostatic consequences of stress, the further problems with readaptation after stress subsides, and the mechanisms and functions of stress enzymes during early mammalian development. The analyses are done with specific concern for their practical impact in assisted reproductive technology (ART) and stem cell technologies.     

Design principles of tissue organisation: How single cells coordinate across scales

Cells act as building blocks of multicellular organisms, forming higher-order structures at different biological scales. Niches, tissues and, ultimately, entire organisms consist of single cells that remain in constant communication. Emergence of developmental patterns and tissue architecture thus relies on single cells acting as a collective, coordinating growth, migration, cell fate transitions and cell type sorting. For this, information has to be transmitted forward from cells to tissues and fed back to the individual cell to allow dynamic and robust coordination. Here, we define the design principles of tissue organisation integrating chemical, genetic and mechanical cues. We also review the state-of-the-art technologies used for dissecting collective cellular behaviours at single cell– and tissue-level resolution. We finally outline future challenges that lie in a comprehensive understanding of how single cells coordinate across biological scales to insure robust development, homoeostasis and regeneration of tissues.     

Correlation between the effects of fosfomycin and chloramphenicol on Escherichia coli

It was speculated that the increase of the UDP-GlcNAc pool observed with chloramphenicol can modulate the residual PEP:UDP-GlcNAc-enolpyruvate activity of fosfomycin-treated cells. This provided an explanation on how chloramphenicol can insure the formation of enough UDP-MurNAc-pentapeptide to sustain peptidoglycan synthesis at a rate that will antagonize fosfomycin-induced lysis.     

Development of HIV fusion inhibitors.

In the past 25 years, the worldwide AIDS epidemic has grown such that roughly 38 million people were estimated to be living with the disease worldwide at the end of 2003. The introduction of antiretroviral-based therapies, beginning in 1987, has enabled many to live with HIV as a chronic, rather than terminal, disease. However, the emergence and spread of drug-resistant strains highlights the continued need for new therapies with novel modes of action. In 2003, the FDA and EMEA approved enfuvirtide (Fuzeon), a 36 amino acid peptide derived from the natural gp41 HR2 sequence, as the first HIV fusion inhibitor. T-1249, a 39 amino acid fusion inhibitor, is active against viruses that develop resistance to enfuvirtide. The development of FIs and the processes to manufacture enfuvirtide and T-1249 on an unprecedented scale for peptide therapeutics are presented. Synthetic routes based on a combination of solid phase peptide synthesis and solution phase fragment condensation as well as the analytical controls necessary to insure a robust process are discussed.     

Growth inhibitory effect of sodium azide in chemosensitivity assays

In vitro chemosensitivity assays based on colony counting are plagued by persistent incidence of false-negative results. To avoid serious predictive errors, some investigators have utilized positive controls (known toxic compounds) as a quality control measure. Sodium azide (NaN3) at 6 mg/ml failed to inhibit colony formation in 17/35 (49%) assays; while in the thymidine incorporation assay, sodium azide was effective in inhibiting 124/131 (95%) specimens. Positive control substances for use in chemosensitivity assays must be carefully selected to insure accurate results.     

Assisted Reproduction and Distributive Justice

The Canadian province of Quebec recently amended its Health Insurance Act to cover the costs of In Vitro Fertilization (IVF). The province of Ontario recently de‐insured IVF. Both provinces cited cost‐effectiveness as their grounds, but the question as to whether a public health insurance system ought to cover IVF raises the deeper question of how we should understand reproduction at the social level, and whether its costs should be a matter of individual or collective responsibility. In this article I examine three strategies for justifying collective provisions in a liberal society and assess whether public reproductive assistance can be defended on any of these accounts. I begin by considering, and rejecting, rights‐based and needs‐based approaches. I go on to argue that instead we ought to address assisted reproduction from the perspective of the contractarian insurance‐based model for public health coverage, according to which we select items for inclusion based on their unpredictability in nature and cost. I argue that infertility qualifies as an unpredictable incident against which rational agents would choose to insure under ideal conditions and that assisted reproduction is thereby a matter of collective responsibility, but only in cases of medical necessity or inability to pay. The policy I endorse by appeal to this approach is a means‐tested system of coverage resembling neither Ontario nor Quebec's, and I conclude that it constitutes a promising alternative worthy of serious consideration by bioethicists, political philosophers, and policy‐makers alike.