“A Devil's Engine”: Photography and Spirits in the Western Solomon Islands

This article looks at photographic practices in Roviana Lagoon in the western Solomon Islands of the South Pacific. It argues that the efficacy or affective power of photographs in this context must be understood in terms of what is locally called maqomaqo (soul or shadow). Photographs contain a material trace of the essence of what they portray, which enables them to “touch” their viewers. This case study allows us to think about the innate metaphysic of photography, and about the way in which “photography” only ever exists as a series of local photographies, which emerge from the interplay between this innate metaphysic of the photographic technology and local ontologies.     

Harmonizing Labeling and Analytical Strategies to Obtain Protein Turnover Rates in Intact Adult Animals

Changes in the abundance of individual proteins in the proteome can be elicited by modulation of protein synthesis (the rate of input of newly synthesized proteins into the protein pool) or degradation (the rate of removal of protein molecules from the pool). A full understanding of proteome changes therefore requires a definition of the roles of these two processes in proteostasis, collectively known as protein turnover. Because protein turnover occurs even in the absence of overt changes in pool abundance, turnover measurements necessitate monitoring the flux of stable isotope–labeled precursors through the protein pool such as labeled amino acids or metabolic precursors such as ammonium chloride or heavy water. In cells in culture, the ability to manipulate precursor pools by rapid medium changes is simple, but for more complex systems such as intact animals, the approach becomes more convoluted. Individual methods bring specific complications, and the suitability of different methods has not been comprehensively explored. In this study, we compare the turnover rates of proteins across four mouse tissues, obtained from the same inbred mouse strain maintained under identical husbandry conditions, measured using either [¹³C₆]lysine or [²H₂]O as the labeling precursor. We show that for long-lived proteins, the two approaches yield essentially identical measures of the first-order rate constant for degradation. For short-lived proteins, there is a need to compensate for the slower equilibration of lysine through the precursor pools. We evaluate different approaches to provide that compensation. We conclude that both labels are suitable, but careful determination of precursor enrichment kinetics in amino acid labeling is critical and has a considerable influence on the numerical values of the derived protein turnover rates.     

Immune Modulation with Sulfasalazine Attenuates Immunopathogenesis but Enhances Macrophage-Mediated Fungal Clearance during Pneumocystis Pneumonia

Although T cells are critical for host defense against respiratory fungal infections, they also contribute to the immunopathogenesis of Pneumocystis pneumonia (PcP). However, the precise downstream effector mechanisms by which T cells mediate these diverse processes are undefined. In the current study the effects of immune modulation with sulfasalazine were evaluated in a mouse model of PcP-related Immune Reconstitution Inflammatory Syndrome (PcP-IRIS). Recovery of T cell-mediated immunity in Pneumocystis-infected immunodeficient mice restored host defense, but also initiated the marked pulmonary inflammation and severe pulmonary function deficits characteristic of IRIS. Sulfasalazine produced a profound attenuation of IRIS, with the unexpected consequence of accelerated fungal clearance. To determine whether macrophage phagocytosis is an effector mechanism of T cell-mediated Pneumocystis clearance and whether sulfasalazine enhances clearance by altering alveolar macrophage phagocytic activity, a novel multispectral imaging flow cytometer-based method was developed to quantify the phagocytosis of Pneumocystis in vivo. Following immune reconstitution, alveolar macrophages from PcP-IRIS mice exhibited a dramatic increase in their ability to actively phagocytose Pneumocystis. Increased phagocytosis correlated temporally with fungal clearance, and required the presence of CD4⁺ T cells. Sulfasalazine accelerated the onset of the CD4⁺ T cell-dependent alveolar macrophage phagocytic response in PcP-IRIS mice, resulting in enhanced fungal clearance. Furthermore, sulfasalazine promoted a TH2-polarized cytokine environment in the lung, and sulfasalazine-enhanced phagocytosis of Pneumocystis was associated with an alternatively activated alveolar macrophage phenotype. These results provide evidence that macrophage phagocytosis is an important in vivo effector mechanism for T cell-mediated Pneumocystis clearance, and that macrophage phenotype can be altered to enhance phagocytosis without exacerbating inflammation. Immune modulation can diminish pulmonary inflammation while preserving host defense, and has therapeutic potential for the treatment of PcP-related immunopathogenesis.     

Development and characterization of a human cell line from an ovarian mixed mullerian tumor (carcinosarcoma)

Summary A cell line derived from a human ovarian carcinosarcoma was established in tissue culture and in nude mice. Two sublines, LDF and HDF, separated by discontinuous density centrifugation were also established from the parent line JoN. The cloning efficiency of the JoN line was 21%. Morphologic features of adenocarcinoma cells characteristic of the parent JoN cells were retained in the sublines and clones; all lines showed the same karyotype and DNA content (pseudodiploid and pseudotetraploid). Keratin, as demonstrated immunohistochemically, was strongly expressed in the parent line JoN and the xenograft tumor, but not at all in the LDF sublines and only moderately in the HDF sublines. Vimentin, however, was expressed in neither the parent line JoN nor the xenograft tumor, but was present in both sublines. Transglutaminase and plasminogen activator activity was high in the parent line JoN. Neither, sublines nor clones showed the same high enzyme activity as the parent line. It is concluded that this human tumor line JoN is comprised of epithelial cells, capable of multidirectional differentiation.     

Systematic Screening of Drosophila Deficiency Mutations for Embryonic Phenotypes and Orphan Receptor Ligands

This paper defines a collection of Drosophila deletion mutations (deficiencies) that can be systematically screened for embryonic phenotypes, orphan receptor ligands, and genes affecting protein localization. It reports the results of deficiency screens we have conducted that have revealed new axon guidance phenotypes in the central nervous system and neuromuscular system and permitted a quantitative assessment of the number of potential genes involved in regulating guidance of specific motor axon branches. Deficiency “kits” that cover the genome with a minimum number of lines have been established to facilitate gene mapping. These kits cannot be systematically analyzed for phenotypes, however, since embryos homozygous for many deficiencies in these kits fail to develop due to the loss of key gene products encoded within the deficiency. To create new kits that can be screened for phenotype, we have examined the development of the nervous system in embryos homozygous for more than 700 distinct deficiency mutations. A kit of ∼400 deficiency lines for which homozygotes have a recognizable nervous system and intact body walls encompasses >80% of the genome. Here we show examples of screens of this kit for orphan receptor ligands and neuronal antigen expression. It can also be used to find genes involved in expression, patterning, and subcellular localization of any protein that can be visualized by antibody staining. A subset kit of 233 deficiency lines, for which homozygotes develop relatively normally to late stage 16, covers ∼50% of the genome. We have screened it for axon guidance phenotypes, and we present examples of new phenotypes we have identified. The subset kit can be used to screen for phenotypes affecting all embryonic organs. In the future, these deficiency kits will allow Drosophila researchers to rapidly and efficiently execute genome-wide anatomical screens that require examination of individual embryos at high magnification.     

Influence of specific growth rate and nutrient limitation upon the sensitivity of Escherichia coli towards chlorhexidine diacetate

The sensitivity of Escherichia coli to chlorhexidine has been assessed for cells grown in a chemostat at a variety of specific growth rates, under conditions of carbon, nitrogen, phosphorus and magnesium limitation. At slow rates of growth (ca 0.08/h) little difference in sensitivity was observed. As growth rate was increased, however, the sensitivity of nitrogen- and carbon-limited cells increased whilst that of magnesium- and phosphate-limited cells decreased. It was not possible to correlate the observed patterns of chlorhexidine sensitivity with any single measure of cell envelope composition (phospholipid content, lipopolysaccharide, envelope proteins, etc.). The results presented are not consistent, therefore, with any simple model for chlorhexidine binding or action and more probably reflect subtle interaction between chlorhexidine, phospholipid-lipopolysaccharide complexes and cations within the envelope.     

Utilisation illégale d’androgènes

Drug abuse for synthetic anabolic androgenic steroids in order to ameliorate sports results is illegal since the law of june 89 in France. No exception whatsoever, therapeutical purpose(s) included, is accepted. Means for controlling such abuse are reviewed briefly here together with data from our research on epitestosterone modifications following physical exercise and testosterone undecanoate controled administration in 15 nor In France the national body responsible for doping analysis in sports is the «Laboratoire National de Dépistage du Dopage» (LNDD). In fact, the control of drug abuse in sports requires laboratory means enabling the detection of banned substances with unlimited certainty. Briefly, untimed urine samples are analyzed for such purpose by gas (liquid or high pressure) chromatography coupled to mass spectrometry (GC/MS) which is the only technique accepted by the medical commission of I.O. C. and relevant bodies world-wide. However, since testosterone itself can now be used as a mean of steroid abuse in man, detection has to solve new problems arising from such manipulation. After considering various approches in order to prove the offense, such as the isotopic ratio for testosterone and different urinary metabolites, and indirect technique, based on the ratio of testosterone to epitestosterone glucuronides, has proved valuable but is now questionned. Epitestosterone is the 17α epimere of testosterone. It is not readily known to clinicians as it has no androgenic potency [5] and does not bind to the specific plasma protein TeBG (26) or androgen receptor [5, 26]. Epitestosterone was first isolated from human urines, simultaneously, by Brooks [6] and Korenman [18]. Wilson and Lipsett [30] among others demonstrated, in man, that this steroid originated both from adrenals and testis, results confirmed recently by Dehennin [8]. Dray et al. and studied its production and circadian rythm in man pointing out that epitestosterone is found in the sulphate fraction of plasma steroids and in the glucuronide fraction of urinary androgen metabolites [12, 20]. Epitestosterone is recovered as such in urines. It is not metabolized [12, 28]. However the pathway for epitestosterone biosynthesis is still uncertain today. The best (for it’s the only one!) hypothesis at present being that of Weustein et al. [30] who reported that epitestosterone could be synthesyzed in man from Δ5 androstène- 3 β, 17α-diol through a possible non enzymic modification of Δ5 androstène-3β, 17β- diol. Donike et al. [10] showed, in man, that the mean GT/GEPIT ratio in urines was 1,5±0,9 (±SD) using epitestosterone as a marker for endogenous androgens. This added index has being implemented, as an official test for androgen abuse’s detection in sports, since the Los Angeles Olympic Games in 1982. All other parameters being normal the definition of a positive androgen doped case is based on GT/GEPIT values over 6. This value of 6 was obtained by adding 6 SD to the mean obtained in man. However, is the use of this parameter justified and 100% safe? Some have questioned its used arguing that epitestosterone, not a well known substance, can not be reliable and could lead to false positive results. We summarize here the results of the French Research Network to which we participated. Mathian et al. [22] showed that epitestosterone production follows testosterone production whatever the age of the subject. The ratio GT/GEPIT doesn’t vary according to age, even over puberty, it remains at 1,40±0,86 from Tanner Stade II to Tanner Stade V. It doesn’t vary significantly after exercise or with fatigue. We also report our study of 15 young men (18–45 year old) over a year. Extensive blood (T, Δ₄, DHT, DHA, SDHA, E2, TeBG, FSH, LH) and urinary parameters (GT, DHT, GEPIT, ADIOL, BDIOL) were measured before, during and after a 21 days course of testosterone undecanoate (TU). Whatever the technique used (GC/MS or RIA) results are identical. We confirmed that GT/GEPIT was very stable for each individual and could be considered as a personnal marker. After TU, at the dosage of 40 to 80 mg/day, GT/GEPIT increased significantly in all instances (athletes and sedentary subjects alike), but not permanently. This change resulted from an increase in testosterone excretion wheras epitestosterone remained non statistically changed. However at the dosage used no permanent modification was found and most of the time GT/GEPIT returned to basal values rapidly. The analysis of the results of our study, according to the limit set by the I.O.C. at 6 for GT/GEPIT, pointed out a lot of false negative (over 50%). Values for GT excretion rate corrected with the creatinine content in the same urinary sample (GT/mg creatinine) have therefore been considered together with GT/GEPIT values. In our opinion, a more suitable and reliable index is thus obtained. The setting of a new limit at 3 for GT/GEPIT (Mean ± 3 SD) together with values under 75 ng/mg creatinine for GT is analyzed. It is also stressed that only a medical commission (aware of the significance of epitestosterone) can interpret the results obtained by analytical chemistry. This is the case in France.     

Angiotensin III and IV activation of the brain AT1 receptor subtype in cardiovascular function

The present investigation determined that native angiotensins II and III (ANG II and III) were equipotent as pressor agents when ICV infused in alert rats, whereas native angiotensin IV (ANG IV) was less potent. An analogue of each of these angiotensins was prepared with a hydroxyethylamine (HEA) amide bond replacement at the N-terminus, yielding additional resistance to degradation. These three angiotensin analogues, HEA-ANG II, HEA-ANG III, and HEA-ANG IV, were equivalent with respect to maximum elevation in pressor responses when ICV infused; and each evidenced significantly extended durations of effect compared with their respective native angiotensin. Comparing analogues, HEA-ANG II had a significantly longer effect compared with HEA-ANG III, and HEA-ANG IV, whereas the latter were equivalent. Pretreatment with the AT₁ receptor subtype antagonist, Losartan (DuP753), blocked subsequent pressor responses to each of these analogues, suggesting that these responses were mediated by the AT₁ receptor subtype. Pretreatment with the specific AT₄ receptor subtype antagonist, Divalinal (HED 1291), failed to influence pressor responses induced by the subsequent infusion of these analogues. These results suggest an important role for Ang III, and perhaps ANG IV, in brain angiotensin pressor responses mediated by the AT₁ receptor subtype.     

Contrasting patterns of density‐dependent selection at different life stages can create more than one fast–slow axis of life‐history variation

There has been much recent research interest in the existence of a major axis of life‐history variation along a fast–slow continuum within almost all major taxonomic groups. Eco‐evolutionary models of density‐dependent selection provide a general explanation for such observations of interspecific variation in the "pace of life." One issue, however, is that some large‐bodied long‐lived “slow” species (e.g., trees and large fish) often show an explosive “fast” type of reproduction with many small offspring, and species with “fast” adult life stages can have comparatively “slow” offspring life stages (e.g., mayflies). We attempt to explain such life‐history evolution using the same eco‐evolutionary modeling approach but with two life stages, separating adult reproductive strategies from offspring survival strategies. When the population dynamics in the two life stages are closely linked and affect each other, density‐dependent selection occurs in parallel on both reproduction and survival, producing the usual one‐dimensional fast–slow continuum (e.g., houseflies to blue whales). However, strong density dependence at either the adult reproduction or offspring survival life stage creates quasi‐independent population dynamics, allowing fast‐type reproduction alongside slow‐type survival (e.g., trees and large fish), or the perhaps rarer slow‐type reproduction alongside fast‐type survival (e.g., mayflies—short‐lived adults producing few long‐lived offspring). Therefore, most types of species life histories in nature can potentially be explained via the eco‐evolutionary consequences of density‐dependent selection given the possible separation of demographic effects at different life stages.