Biological weapons

Bioterrorism is defined by the intentional or threatened of microorganisms or toxins derived from living organisms to cause death or diseases in humans, animals or plants on which we depend. The other major point is to generate fear in the population. More than 180 pathogens have been reported to be potential agents for bioterrorism. The following is an overview of several agents that could be involved in a biological attack.     

What is the environment in environmental health research? Perspectives from the ethics of science

Environmental health research produces scientific knowledge about environmental hazards crucial for public health and environmental justice movements that seek to prevent or reduce exposure to these hazards. The environment in environmental health research is conceptualized as the range of possible social, biological, chemical, and/or physical hazards or risks to human health, some of which merit study due to factors such as their probability and severity, the feasibility of their remediation, and injustice in their distribution. This paper explores the ethics of identifying the relevant environment for environmental health research, as judgments involved in defining an environmental hazard or risk, judgments of that hazard or risk's probability, severity, and/or injustice, as well as the feasibility of its remediation, all ought to appeal to non-epistemic as well as epistemic values. I illustrate by discussing the case of environmental lead, a housing-related hazard that remains unjustly distributed by race and class and is particularly dangerous to children. Examining a controversy in environmental health research ethics where researchers tested multiple levels of lead abatement in lead-contaminated households, I argue that the broader perspective on the ethics of environmental health research provided in the first part of this paper may have helped prevent this controversy.     

Alzheimer's disease: fundamental and therapeutic aspects

Alzheimer's disease is the most common type of progressive and debilitating dementia affecting aged people. In some early — as well as late-onset familial cases, a genetic linkage with chromosomes 14, 21 (early-onset) or 19 (late-onset) has been indicated. Furthermore, a direct or indirect role has been attributed to normal or structurally altered amyloid -protein (concentrated in senile plaques) and/or excessively phosphorylated tau protein (located in neurofibrillary tangles). Degeneration of cholinergic neurons and concomitant impairment of cortical and hippocampal neurotransmission lead to cognitive and memory deficits. Several compounds are being tested in attempts to prevent and/or cure Alzheimer's disease, including tacrine, which has very modest efficacy in a sub-group of patients, and new acetylcholinesterase inhibitors. Pilot experiments have also been launched using nerve growth factor (NGF) to prevent or stabilize the processes of cholinergic pathway degeneration. Alternatively, antioxidants, free radical scavengers and/or non steroidal anti-inflammatory agents may be screened as potential therapies for neurodegenerative diseases induced by multiple endogenous and/or exogenous factors. The recent use of transgenic mice, in parallel with other genetic, biochemical and neurobiological systems, in vivo and/or in vitro (cell cultures), should accelerate the discovery and development of specific drugs for the treatment of Alzheimer's disease.     

The normativity of artefacts

Part of the distinction between artefacts, objects made by humans for particular purposes, and natural objects is that artefacts are subject to normative judgements. A drill, say, can be a good drill or a poor drill, it can function well or correctly or it can malfunction. In this paper I investigate how such judgements fit into the domain of the normative in general and what the grounds for their normativity are. Taking as a starting point a general characterization of normativity proposed by Dancy, I argue how statements such as ‘this is a good drill’ or ‘this drill is malfunctioning’ can be seen to express normative facts, or the content of normative statements. What they say is that a user who has a desire to achieve a particular relevant outcome has a reason to use, or not to use, the artefact in question. Next this analysis is extended to show that not just statements that say that an artefact performs its function well or poorly, but all statements that ascribe a function to an artefact can be seen as expressing a normative fact. On this approach the normativity of artefacts is analyzed in terms of reasons on grounds of practical, and to a lesser extent theoretical, rationality. I close by investigating briefly to what extent reasons on moral grounds are, in the analysis adopted here, involved in the normativity of artefacts.     

Effects of insulin on plasma fibrinogen levels in rats submitted to tissue injury or ACTH administration.

Insulin is necessary to produce an increase of plasma fibrinogen in rats submitted to tissue injury or ACTH administration. This increase is more significant when endogenous or exogenous excess of insulin is present, while in uninjured rats the absence or excess insulin does not modify plasma fibrinogen.     

Response ofPhloeotribus scarabaeoides (Coleoptera,Scolytidae) to ethylene in an olfactometer

The role of ethylene, pure or in formulation, in the colonization behaviour of the olive bark beetle,Phloeotribus scarabaeoides (Coleoptera, Scolytidae) has been investigated in the laboratory. Ethylene has been found to be attractive in both sexes; the formulation ethrel 48 was active in an olfactometer up to several months. Ethylene, whose concentration varies with the developmental stage or the condition of the tree or its wood, may play an important role in the primary attraction of these scolytids to their host.     

Odor maps in the brain: Spatial aspects of odor representation in sensory surface and olfactory bulb

The olfactory sense detects and distinguishes a multitude of different odors. Recent progress in molecular as well as physiological approaches has elucidated basic principles of neuronal encoding of odorants, common to insects and vertebrates. The construction of neuronal representations for odors begins with the task of mapping the multidimensional odor space onto the two-dimensional sensory surface, and subsequently onto the olfactory bulb or antennal lobe. A distributed expression of odorant receptors, albeit restricted to subregions of the sensory surface (large, intermediate or small for zebrafish, mouse or drosophila, respectively), ensures a robust representation, insensitive to mechanical insult. Olfactory receptor neurons expressing the same odorant receptors converge to form a receptotopic map in the olfactory bulb or antennal lobe. The emerging coding principle is a chemotopic representation of odorants at the first brain level, realized either as combinatorial or as monospecific representation, depending on the odorant.     

Failure of medial forebrain bundle or raphe ablation to alter the daily temperature rhythm of the rat.

The data presented in the present study suggest that neither the ascending noradrenergic fibres confined to the MFB nor the serotonergic fibres originating in or passing through the mesencephalic raphe are essential for periodicity in body temperature. Both control and experimental groups, i.e., rats subjected to medial forebrain bundle or raphe ablation presented circadian periodicity in body temperature and neither the phase, amplitude or overall mean of experimentals differed significantly from controls.     

Effects of insulin on plasma fibrinogen levels in rats submitted to tissue injury or ACTH administration

Summary Insulin is necessary to produce an increase of plasma fibrinogen in rats submitted to tissue injury or ACTH administration. This increase is more significant when endogenous or exogeneous excess of insulin is present, while in uninjured rats the absence or excess of insulin does not modify plasma fibrinogen.     

Protein surface similarities: a survey of methods to describe and compare protein surfaces

Many methods have been developed to analyse protein sequences and structures, although less work has been undertaken describing and comparing protein surfaces. Evolution can lead sequences to diverge or structures to change topology; nevertheless, surface determinants that are essential to protein function itself may be mantained. Moreover, different molecules could converge to similar functions by gaining specific surface determinants. In such cases, sequence or structure comparisons are likely to be inadequate in describing or identifying protein functions and evolutionary relationships among proteins. Surface analysis can identify function determinants that are independent of sequence or secondary structure and can therefore be a powerful tool to highlight cases of possible convergent or divergent evolution. This kind of approach can be useful for a better understanding of protein molecular and biochemical mechanisms of catalysis or interaction with a ligand, which are usually surface dependent. Protein surface comparison, when compared to sequence or structure comparison methods, is a hard computational challenge and evaluated methods allowing the comparison of protein surfaces are difficult to find. In this review, we will survey the current knowledge about protein surface similarity and the techniques to detect it.     

Faithful after break-up: suppression of chromosomal translocations

Chromosome integrity in response to chemically or radiation-induced chromosome breaks and the perturbation of ongoing replication forks relies on multiple DNA repair mechanisms. However, repair of these lesions may lead to unwanted chromosome rearrangement if not properly executed or regulated. As these types of chromosomal alterations threaten the cell’s and the organism’s very own survival, multiple systems are developed to avoid or at least limit break-induced chromosomal rearrangements. In this review, we highlight cellular strategies for repressing DNA break-induced chromosomal translocations in multiple model systems including yeast, mouse, and human. These pathways select proper homologous templates or broken DNA ends for the faithful repair of DNA breaks to avoid undesirable chromosomal translocations.     

In vivo measurement, by differential pulse voltammetry, of 5-HIAA in the striatum of the rat

Differential pulse voltammetry, performed with electrically treated carbon fiber electrodes, enables us to detect in vitro or in vivo in the striatum of anesthetized Rats, an oxidation peak 3 at a potential of +300 mV. Electrolytic, or 5,7-dihydroxytryptamine lesions of the medial forebrain bundle are followed by a decrease of respectively 59 and 62% of this peak. Biochemical measurements are significantly correlated to the measured peaks 3 and troughs. Thus, peak 3 increases obtained after injection of L-tryptophane and/or reserpine, as well as the troughs observed after injection of clorgyline and/or NSD 1015 confirm that the peak 3 is dependent upon 5-hydroxyindolacetic acid (5-HIAA) concentration.     

Psychrophilic and psychrotrophic microorganisms

Psychrophilic and psychrotrophic microorganisms have the ability to grow at 0 degree C. Psychrotrophic microorganisms have a maximum temperature for growth above 20 degrees C and are widespread in natural environments and in foods. Psychrophilic microorganisms have a maximum temperature for growth at 20 degrees C or below and are restricted to permanently cold habitats. This ability to grow at low temperature may be correlated with a lower temperature characteristic than that of the mesophiles, an increasing proportion of unsaturated fatty acids in the lipid phase of the cell membrane, which makes it more fluid, and a protein conformation functional at low temperature. The relatively low maximum temperature of growth for these microorganisms is often considered to be due to the thermolability of one or more essential cellular components, particularly enzymes, while some degradative activities are enhanced, resulting in an exhaustion of cell energy, a leakage of intracellular substances or complete lysis. Psychrotrophic microorganisms are well-known for their degradative activities in foods. Some are pathogenic or toxinogenic for man, animals or plants. However in natural microbial ecosystems psychrotrophic and psychrophilic microorganisms can play a large role in the biodegradation of organic matter during cold seasons.     

Neuformulierung der Kristallographie

Summary A consideration of symmetry in any object or process entails essentially a correlation between parts of a unit or between unit and unit. Enquiry must be made as to what is geometrically distinguishable or indistinguishable and an attempt undertaken to discover the pattern underlying apparent disorder.Crystallography has been the science in which the principles of symmetry have been most extensively applied and received their fullest development. Naturally enough, the system evolved for formulating the symmetry inherent in crystals has been adapted to the specific problems the crystallographer sets out to solve.Such researches, however, go far beyond the bounds of ordinary geometric crystallography and are, in particular, an essential requisite for mastering the problems of stereochemistry. It is, therefore, obviously desirable to find a method of formulation which can be applied to any or all the problems in which the question of symmetry arises, such as the systematic ambiguities or the possible deformations of objects or processes endowed with symmetry. To this end the Element of Symmetry, traditional starting point of investigations into symmetry, must be replaced by the covering operations as such.Symmetry formulæ can be deduced, which beyond merely describing the features involved, permit the detailed numerical calculation of their development and variation. In this respect they must prove of value not only to the chemist in his investigation of isomers etc., but can usefully be adopted also by the crystallographer.A short introduction into this new method of formulation is given in the preceding pages.     

Failure of medial forebrain bundle or raphe ablation to alter the daily temperature rhythm of the rat

Summary The data presented in the present study suggest that neither the ascending noradrenergic fibres confined to the MFB nor the serotonergic fibres originating in or passing through the mesencephalic raphe are essential for periodicity in body temperature. Both control and experimental groups, i.e., rats subjected to medial forebrain bundle or raphe ablation presented circadian periodicity in body temperature and neither the phase, amplitude or overall mean of experimentals differed significantly from controls.     

The use of significance limits in graphical data representations

Summary Significance limits are proposed as an alternative to the use of standard deviation, standard error, or confidence or tolerance limits when experimental data are presented in a graphical form. This measurement of uncertainty allows graphical t-tests to be used both for the estimation of data variance and for an approximate statistical comparison between two or more data sets.     

Inhibition of the reinitiation of meiosis in Xenopus laevis oocytes by three natural antiproteases: antipain, chymostatin, and leupeptin]

Oocytes incubated for 1 hr. in saline containing 1 mg/ml of antipain, leupeptin or chymostatin do not reinstate meiosis when progesterone or ionophore A 23187 are added. On the contrary such oocytes remain able to undergo meiosis when injected with cytoplasm of maturing oocytes (MPF), with Rabbit phosphorylase kinase or with Beef protein kinase. These results demonstrate that the loss of responsiveness to progesterone or ionophore is not due to toxic effects but rather to some interference with a key event which occurs prior to MPF action.     

The action of various vitamin D3 metabolites on calcium and phosphorus metabolism in chick embryo calvariae

Chick embryos from vitamin D-deficient hens given physiological doses of 1,25-dihydroxyvitamin D3 or 24,25-dihydroxyvitamin D3 or both become severely hypocalcemic, hyperphosphatemic and fail to hatch as compared to those derived from hens given 25-hydroxyvitamin D3 or 24,25-difluoro-25-hydroxyvitamin D3. Calvariae from the former contain less mineral and on incubation in vitro produce significantly lower calcium and higher phosphate concentration in the medium than do the calvariae derived from the embryos of hens supported on 25-hydroxyvitamin D3 or 24,24-difluoro-25-hydroxyvitamin D3.     

Selection of high-level abamectin resistance from field-collected house flies, Musca domestica

Abamectin is a novel, highly promising insecticide with activity against many pests. To determine if resistance to abamectin could occur, we collected house flies from several New York dairies and selected them in the laboratory. Resistance developed rapidly and to a high level (36 or greater than 60,000-fold, depending upon test technique and/or adjuvant) that could not be overcome by the synergists piperonyl butoxide or S,S,S-tributylphosphorotrithioate. There was no increase in (cross)resistance to crotoxyphos, dichlorvos, dimethoate, tetrachlorvinphos, permethrin, dieldrin or lindane following abamectin selection. Our results suggest the potential for abamectin resistance is high, at least in house flies, and that the judicious use of abamectin will be needed to prolong its usefulness as an insecticide.     

Membrane trafficking in neuronal maintenance and degeneration

Defects in membrane trafficking and degradation are hallmarks of most, and maybe all, neurodegenerative disorders. Such defects typically result in the accumulation of undegraded proteins due to aberrant endosomal sorting, lysosomal degradation, or autophagy. The genetic or environmental cause of a specific disease may directly affect these membrane trafficking processes. Alternatively, changes in intracellular sorting and degradation can occur as cellular responses of degenerating neurons to unrelated primary defects such as insoluble protein aggregates or other neurotoxic insults. Importantly, altered membrane trafficking may contribute to the pathogenesis or indeed protect the neuron. The observation of dramatic changes to membrane trafficking thus comes with the challenging need to distinguish pathological from protective alterations. Here, we will review our current knowledge about the protective and destructive roles of membrane trafficking in neuronal maintenance and degeneration. In particular, we will first focus on the question of what type of membrane trafficking keeps healthy neurons alive in the first place. Next, we will discuss what alterations of membrane trafficking are known to occur in Alzheimer’s disease and other tauopathies, Parkinson’s disease, polyQ diseases, peripheral neuropathies, and lysosomal storage disorders. Combining the maintenance and degeneration viewpoints may yield insight into how to distinguish when membrane trafficking functions protectively or contributes to degeneration.