Expression of prolyl hydroxylase domains, the upstream regulators of HIF, in the brain of the anoxia-tolerant crucian carp during anoxia-reoxygenation.

The hypoxia-inducible factor (HIF) is considered key in the transcriptional response to low oxygen. Yet, the role of HIF in the absence of oxygen (anoxia) and in preparation for reoxygenation remains unclear. Recent studies suggest that mounting a HIF response may be counterproductive for anoxia survival. We here studied one of the champions of anoxia survival, the crucian carp (Carassius carassius), and hypothesized that expression of prolyl hydroxylase domains (PHDs; the upstream regulators of HIF) are upregulated to circumvent an energy-costly activation of HIF in anoxia and to prepare for reoxygenation. We measured whole brain mRNA and protein levels of the three isoforms PHD1, PHD2, and PHD3, coded for by multiple paralogs of the genes egln2, egln1, and egln3, using quantitative PCR and Western blotting in the brain of crucian carps exposed to 5 days normoxia or anoxia, and 5 days anoxia followed by 3 or 24 h of reoxygenation. The mRNA levels of most egln paralogs were increased in anoxia and upon reoxygenation, with egln3 showing the largest increase in mRNA level (up to 17-fold) and highest relative mRNA abundance (up to 75% of expressed egln). The protein level of all PHDs was maintained in anoxia and increased upon reoxygenation. We then explored PHD distribution in different brain regions and found PHD immunoreactivity to be associated with axonal branches and showing region-specific changes during anoxia-reoxygenation. Our results support an overall upregulation of egln under prolonged anoxia and PHDs upon reoxygenation in crucian carp, likely aimed at suppressing HIF responses, although regional differences are apparent in such a complex organ as the brain.NEW & NOTEWORTHY We report a profound upregulation of most egln paralog mRNA levels in anoxia and upon reoxygenation, with egln3ii showing the largest, a 17-fold increase, and highest relative mRNA abundance. The relative abundance of prolyl hydroxylase domain (PHD) proteins was maintained during anoxia and increased at reoxygenation. PHD immunoreactivity was localized to axonal branches with region-specific changes during anoxia-reoxygenation. These dynamic and regional changes in crucian carp, champion of anoxia tolerance, are most likely adaptive and call for further mechanistic studies.

Locust gut epithelia do not become more permeable to fluorescent dextran and bacteria in the cold.

The insect gut, which plays a role in ion and water balance, has been shown to leak solutes in the cold. Cold stress can also activate insect immune systems, but it is unknown whether the leak of the gut microbiome is a possible immune trigger in the cold. We developed a novel feeding protocol to load the gut of locusts (Locusta migratoria) with fluorescent bacteria before exposing them to -2°C for up to 48 h. No bacteria were recovered from the hemolymph of cold-exposed locusts, regardless of exposure duration. To examine this further, we used an ex vivo gut sac preparation to re-test cold-induced fluorescent FITC-dextran leak across the gut and found no increased rate of leak. These results question not only the validity of FITC-dextran as a marker of paracellular barrier permeability in the gut, but also to what extent the insect gut becomes leaky in the cold.

From middle-class American women to French managers: The transatlantic trajectory of assertiveness training, c. 1950s-1980s.

This article explores the contribution of behavior therapy to the extension of psychotherapeutic notions and techniques into everyday life, focusing on the transatlantic trajectory of assertiveness training. It traces the history of this behavioral intervention into interindividual relations from its emergence as a treatment for anxiety in postwar United States to its importation into the French field of continuing professional training at the turn of the 1980s. To understand what traveled between countries and practical fields, I first consider the definition of assertiveness as a skill sitting halfway between passivity and aggressiveness, which developed in the United States along with its uses outside therapy. I relate the success and inflexions undergone by assertiveness training between the 1950s and the 1970s to theoretical and strategic innovations in behavioral therapy and psychology, as well as to the reception of political and social movements, especially the women's movement. This article also shows that what moved between countries, sectors, and target audiences was not only an understanding of assertiveness as a socially acceptable expression of feelings, needs, and wants, but also diagnostic and action scripts fueled by the "ferment" of the 1960s. From middle-class American women to French managers, the expanded applications of assertiveness training were justified by the rhetoric of tensions between role socialization and new expectations for self-fulfillment and efficiency. Following the behavioral deficit model emphasized in assertiveness training, increasing calls for self-expression and participation prescribed communication skill training and a reconfiguration of interpersonal relations, both in the private and the work sphere. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Cold-induced metabolic depression in cunner (Tautogolabrus adspersus): A multifaceted cellular event.

Metabolic depression and dormancy (i.e., stopping/greatly reducing activity and feeding) are strategies used by many animals to survive winter conditions characterized by food shortages and cold temperatures. However, controversy exists on whether the reduced metabolism of some fishes at cold temperatures is due to dormancy alone, or also involves active metabolic depression. Thus, we acclimated winter-dormant cunner [Tautogolabrus adspersus, a north temperate wrasse which in Newfoundland is at the northern limit of its distribution] and winter-active Atlantic salmon (Salmo salar) to winter (0°C; 8h light: 16h dark) and summer (10°C; 16h light: 8 h dark) conditions, and measured the thermal sensitivity of ATP-producing and O2-consuming processes in isolated liver mitochondria and hepatocytes when exposed in vitro to temperatures from 20 to 0°C and 10 to 0°C, respectively. We found that: 1) liver mitochondrial State 3 respiration and hepatocyte O2 consumption in cunner were only ~ one-third and two-thirds of that measured in salmon, respectively, at all measurement temperatures; 2) cunner mitochondria also have proton conductance and leak respiration (State 4) values that are only approximately one-third of those in salmon; 3) the mitochondria of cunner show a dramatic reduction in respiratory control ratio (from ~ 8 to 3), and a much greater drop in State 3 respiration, between 10 and 5°C (Q10 values in 10- and 0°C-acclimated fish of 14.5 and 141.2, respectively), as compared with salmon (3.9 and 9.6, respectively); and 4) lowering temperature from 5 to 0°C resulted in ~ 40 and 30% reductions in hepatocyte O2 consumption due to non-mitochondrial respiration and Na+-K+-ATPase activity, respectively, in cunner, but not in salmon. Collectively, these results highlight the intrinsic capacity for metabolic depression in hepatocytes and mitochondria of cunner, and clearly suggest that several cellular processes play a role in the reduced metabolic rates exhibited by some fishes at cold temperatures.

Putting psychotherapy in its place: The regionalization of behavior therapy in France, Switzerland, and Belgium, 1960s-1990s.

This article traces the history of the behavior therapy movement in French-speaking Europe between the 1960s and the 1990s, focusing on its geographically located development, whether on a national, sub- or supra-national scale. By examining the trajectories of the three main behavioral therapy associations in France, Switzerland, and Belgium, we show that it is not possible to subsume them under a common intellectual history. Despite the importance of theoretical debates in the emergence of this brand of psychotherapy in English-speaking countries, adherence to this type of explanation falls short of accounting for the differential reception of behavioral therapies in these countries. We argue that the later development of behavioral therapy in France, Belgium, and Switzerland was shaped more by professional agendas, local definitions, and regulations of psychotherapy than by "pure" theoretical commitments and conflicts between schools of thought. From a historiographical perspective, exploring the regionalization of psychotherapeutic styles thus involves contesting the idea that different therapies are mainly characterized by adherence to psychological theories and embedded ontologies of the self that are radically opposed (i.e., humanism vs. naturalism, psychoanalysis vs. behavior therapy). Localizing psychotherapies and paying attention to the varying circumstances and traditions in which they have evolved allows us to go beyond this dichotomous vision and to access a multiplicity of nondogmatic and intermediate positions that would otherwise be invisible.

The Relationship between Myoglobin, Aerobic Capacity, Nitric Oxide Synthase Activity and Mitochondrial Function in Fish Hearts.

The dynamic interactions between nitric oxide (NO) and myoglobin (Mb) in the cardiovascular system have received considerable attention. The loss of Mb, the principal O2 carrier and a NO scavenger/producer, in the heart of some red-blooded fishes provides a unique opportunity for assessing this globin's role in NO homeostasis and mitochondrial function. We measured Mb content, activities of enzymes of NO and aerobic metabolism [NO Synthase (NOS) and citrate synthase, respectively] and mitochondrial parameters [Complex-I and -I+II respiration, coupling efficiency, reactive oxygen species production/release rates and mitochondrial sensitivity to inhibition by NO (i.e., NO IC50)] in the heart of three species of red-blooded fish. The expression of Mb correlated positively with NOS activity and NO IC50, with low NOS activity and a reduced NO IC50 in the Mb-lacking lumpfish (Cyclopterus lumpus) as compared to the Mb-expressing Atlantic salmon (Salmo salar) and short-horned sculpin (Myoxocephalus scorpius). Collectively, our data show that NO levels are fine-tuned so that NO homeostasis and mitochondrial function are preserved; indicate that compensatory mechanisms are in place to tightly regulate [NO] and mitochondrial function in a species without Mb; and strongly suggest that the NO IC50 for oxidative phosphorylation is closely related to a fish's hypoxia tolerance.

Osmoregulatory capacity at low temperature is critical for insect cold tolerance.

At low temperature many insects lose extracellular ion homeostasis and the capacity to mitigate homeostatic imbalance determines their cold tolerance. Extracellular homeostasis is ensured by the osmoregulatory organs and recent research has emphasized key roles for the Malpighian tubules and hindgut in modulating insect cold tolerance. Here, we review the effects of low temperature on transport capacity of osmoregulatory organs and outline physiological processes leading from cold exposure to disruption of ion homeostasis and cold-injury in insects. We show how cold adaptation and cold acclimation are associated with physiological modifications to transport capacity in Malpighian tubules and hindgut. These responses mitigate loss of homeostasis and we highlight how further study of molecular and cellular mechanisms are critical to fully appreciate the adaptations that facilitate insect cold tolerance.

Acclimation to warm temperatures has important implications for mitochondrial function in Atlantic salmon (Salmo salar).

In fish, the capacity of thermal acclimation to preserve cardiac mitochondrial function under future warming scenarios is important to understand given the central roles that cardiac energy metabolism and performance play in this taxa's thermal tolerance. We acclimated Atlantic salmon to 12 and 20°C (for >2 months), and investigated the effects of acute and chronic warming on cardiac mitochondrial respiration and reactive oxygen species (ROS) production (release rate) using high-resolution fluorespirometry. Further, we compared the sensitivity of mitochondrial respiration to nitric oxide (i.e. the NO IC50), and assessed the mitochondrial response to anoxia-reoxygenation (AR). Acute exposure to 20°C increased maximal mitochondrial respiration by ∼55%; however, the mitochondria's complex I respiratory control ratio was 17% lower and ROS production was increased by ≥60%. Acclimation to 20°C: (1) preserved mitochondrial coupling and aerobic capacity; (2) decreased the mitochondria's ROS production by ∼30%; (3) increased the mitochondria's NO IC50 by ∼23%; and (4) improved mitochondrial membrane integrity at 20°C. AR did not affect mitochondrial function at 12°C, but acute exposure to 20°C and AR depressed maximal mitochondrial respiration (by ∼9%) and coupling (by ∼16%) without impacting ROS production. Finally, warm acclimation did not improve the capacity of mitochondria to recover from AR, indicating that there was no 'cross-tolerance' between these challenges. Our findings provide compelling evidence that thermal plasticity of cardiac mitochondrial function contributes to the Atlantic salmon's capability to survive at ≥20°C for prolonged periods, but call into question whether this plasticity may allow them to withstand high temperatures when combined with other stressors.

Cold acclimation preserves hindgut reabsorption capacity at low temperature in a chill-susceptible insect, Locusta migratoria.

Cold acclimation increases cold tolerance of chill-susceptible insects and the acclimation response often involves improved organismal ion balance and osmoregulatory function at low temperature. However, the physiological mechanisms underlying plasticity of ion regulatory capacity are largely unresolved. Here we used Ussing chambers to explore the effects of cold exposure on hindgut KCl reabsorption in cold- (11 °C) and warm-acclimated (30 °C) Locusta migratoria. Cooling (from 30 to 10 °C) reduced active reabsorption across recta from warm-acclimated locusts, while recta from cold-acclimated locusts maintained reabsorption at 10 °C. The differences in transport capacity were not linked to major rearrangements of membrane phospholipid profiles. Yet, the stimulatory effect of two signal transduction pathways were altered by temperature and/or acclimation. cAMP-stimulation increased reabsorption in both acclimation groups, with a strong stimulatory effect at 30 °C and a moderate stimulatory effect at 10 °C. cGMP-stimulation also increased reabsorption in both acclimation groups at 30 °C, but their response to cGMP differed at 10 °C. Recta from warm-acclimated locusts, characterised by reduced reabsorption at 10 °C, recovered reabsorption capacity following cGMP-stimulation at 10 °C. In contrast, recta from cold-acclimated locusts, characterised by sustained reabsorption at 10 °C, were unaffected by cGMP-stimulation. Furthermore, cold-exposed recta from warm-acclimated locusts were insensitive to bafilomycin-α1, a V-type H+-ATPase inhibitor, whereas this blocker reduced reabsorption across cold-exposed recta from cold-acclimated animals. In conclusion, bafilomycin-sensitive and cGMP-dependent transport mechanism(s) are likely blocked during cold exposure in warm-acclimated animals while preserved in cold-acclimated animals. These may in part explain the large differences in rectal ion transport capacity between acclimation groups at low temperature.

Improved mitochondrial function in salmon (Salmo salar) following high temperature acclimation suggests that there are cracks in the proverbial 'ceiling'.

Mitochondrial function can provide key insights into how fish will respond to climate change, due to its important role in heart performance, energy metabolism and oxidative stress. However, whether warm acclimation can maintain or improve the energetic status of the fish heart when exposed to short-term heat stress is not well understood. We acclimated Atlantic salmon, a highly aerobic eurythermal species, to 12 and 20 °C, then measured cardiac mitochondrial functionality and integrity at 20 °C and at 24, 26 and 28 °C (this species' critical thermal maximum ± 2 °C). Acclimation to 20 °C vs. 12 °C enhanced many aspects of mitochondrial respiratory capacity and efficiency up to 24 °C, and preserved outer mitochondrial membrane integrity up to 26 °C. Further, reactive oxygen species (ROS) production was dramatically decreased at all temperatures. These data suggest that salmon acclimated to 'normal' maximum summer temperatures are capable of surviving all but the most extreme ocean heat waves, and that there is no 'tradeoff' in heart mitochondrial function when Atlantic salmon are acclimated to high temperatures (i.e., increased oxidative phosphorylation does not result in heightened ROS production). This study suggests that fish species may show quite different acclimatory responses when exposed to prolonged high temperatures, and thus, susceptibility to climate warming.

The art of growing old: environmental manipulation, physiological rhythms, and the advent of Microcebus murinus as a primate model of aging.

In the early 1990s, Microcebus murinus, a small primate endemic to Madagascar, emerged as a potential animal model for the study of aging and Alzheimer's disease. This paper traces the use of the lesser mouse lemur in research on aging and associated neurodegenerative diseases, focusing on a basic material precondition that made this possible, namely, the conversion of a wild animal into an experimental organism that lives, breeds, and survives in the laboratory. It argues that the "old" mouse lemur model can be considered as an eco-zootechnical acquisition. This is shown by examining how, since the early 1970s, French mouse lemur researchers have articulated colony productivity and viability with the influence of environmental factors on the demographics and physiology of the species. The appearance and maintenance of a growing number of old mouse lemurs in French research facilities are related to three developments: the application of the ecological notion of "social stress" to the understanding and management of the behavior of the captive population; the experimental demonstration that a variety of seasonal physiological changes in the species were influenced by the photoperiod; and the related attempt to accelerate aging in mouse lemurs through the manipulation of annual light conditions.

Learning to stand tall: Idiopathic scoliosis, behavioral electronics, and technologically-assisted patient participation in treatment, c. 1969-1992.

Drawing on the archives of American learning psychologist Neal E. Miller, this article investigates the role of instrumentation in the expansion and diversification of the behavior therapy domain from the late 1960s to the early 1990s. Through the case of Miller's research on the use of biofeedback to treat idiopathic scoliosis, it argues that the post-World War II adoption of electronic technology by behavioral psychologists contributed to extending their subject matter to include physiological processes and somatic conditions. It also enabled a technologically-instrumented move outside the laboratory through the development of portable ambulatory treatment devices. Using the example of the Posture-Training Device that Miller and his collaborators invented for the behavioral treatment of idiopathic scoliosis, this paper considers how electromechanical psychological instrumentation illustrated a larger and ambiguous strategic shift in behavior therapy from an orientation toward external control to one of self-control.

Cardiac mitochondrial function, nitric oxide sensitivity and lipid composition following hypoxia acclimation in sablefish.

In fishes, the effect of O2 limitation on cardiac mitochondrial function remains largely unexplored. The sablefish (Anoplopoma fimbria) encounters considerable variations in environmental oxygen availability, and is an interesting model for studying the effects of hypoxia on fish cardiorespiratory function. We investigated how in vivo hypoxia acclimation (6 months at 40% then 3 weeks at 20% air saturation) and in vitro anoxia-reoxygenation affected sablefish cardiac mitochondrial respiration and reactive oxygen species (ROS) release rates using high-resolution fluorespirometry. Further, we investigated how hypoxia acclimation affected the sensitivity of mitochondrial respiration to nitric oxide (NO), and compared mitochondrial lipid and fatty acid (FA) composition between groups. Hypoxia acclimation did not alter mitochondrial coupled or uncoupled respiration, or respiratory control ratio, ROS release rates, P50 or superoxide dismutase activity. However, it increased citrate synthase activity (by ∼20%), increased the sensitivity of mitochondrial respiration to NO inhibition (i.e., the NO IC50 was 25% lower), and enhanced the recovery of respiration (by 21%) and reduced ROS release rates (by 25-30%) post-anoxia. In addition, hypoxia acclimation altered mitochondrial FA composition [increasing arachidonic acid (20:4ω6) and eicosapentaenoic acid (20:5ω3) proportions by 11 and 14%, respectively], and SIMPER analysis revealed that the phospholipid:sterol ratio was the largest contributor (24%) to the dissimilarity between treatments. Overall, these results suggest that hypoxia acclimation may protect sablefish cardiac bioenergetic function during or after periods of O2 limitation, and that this may be related to alterations in mitochondrial sensitivity to NO and to adaptive changes in membrane composition (fluidity).

Effects of anoxia on ATP, water, ion and pH balance in an insect (Locusta migratoria).

When exposed to anoxia, insects rapidly go into a hypometabolic coma from which they can recover when exposed to normoxia again. However, prolonged anoxic bouts eventually lead to death in most insects, although some species are surprisingly tolerant. Anoxia challenges ATP, ion, pH and water homeostasis, but it is not clear how fast and to what degree each of these parameters is disrupted during anoxia, nor how quickly they recover. Further, it has not been investigated which disruptions are the primary source of the tissue damage that ultimately causes death. Here, we show, in the migratory locust (Locusta migratoria), that prolonged anoxic exposures are associated with increased recovery time, decreased survival, rapidly disrupted ATP and pH homeostasis and a slower disruption of ion ([K+] and [Na+]) and water balance. Locusts could not fully recover after 4 h of anoxia at 30°C, and at this point hemolymph [K+] was elevated 5-fold and [Na+] was decreased 2-fold, muscle [ATP] was decreased to ≤3% of normoxic values, hemolymph pH had dropped 0.8 units from 7.3 to 6.5, and hemolymph water content was halved. These physiological changes are associated with marked tissue damage in vivo and we show that the isolated and combined effects of hyperkalemia, acidosis and anoxia can all cause muscle tissue damage in vitro to equally large degrees. When locusts were returned to normoxia after a moderate (2 h) exposure of anoxia, ATP recovered rapidly (15 min) and this was quickly followed by recovery of ion balance (30 min), while pH recovery took 2-24 h. Recovery of [K+] and [Na+] coincided with the animals exiting the comatose state, but recovery to an upright position took ∼90 min and was not related to any of the physiological parameters examined.

Cold tolerance is linked to osmoregulatory function of the hindgut in Locusta migratoria.

There is growing evidence that maintenance of ion and water balance determines cold tolerance in many insects. The hindgut of terrestrial insects is critical for maintaining organismal homeostasis as it regulates solute and water balance of the haemolymph. Here, we used ex vivo everted gut sacs of Locustamigratoria to examine the effects of temperature (0-30°C), thermal acclimation, hypoxia, and ionic and osmotic forces on bulk water and ion (Na+, K+ and Cl-) movement across the rectal epithelium. These findings were related to simultaneous in vivo measurements of water and ion balance in locusts exposed to similar temperatures. As predicted, we observed a critical inhibition of net water and ion reabsorption at low temperature that was proportional to the in vivo loss of water and ion homeostasis. Further, cold-acclimated locusts, which are known to defend ion and water balance at low temperature, were characterised by improved reabsorptive capacity at low temperature. These findings strongly support the hypothesis that transport mechanisms in the hindgut at low temperature are essential for cold tolerance. The loss of osmoregulatory capacity at low temperature was primarily caused by reduced active transport, while rectal paracellular permeability to fluorescein isothiocyanate dextran was unchanged at 0 and 30°C. During cold exposure, water reabsorption was independent of major cation gradients across the epithelia, while a reduction in mucosal Cl- availability and an increase in mucosal osmolality markedly depressed water reabsorption. These findings are discussed in the context of existing knowledge and with suggestions for future physiological studies on cold acclimation and adaptation in insects.

Dynamic changes in nitric oxide synthase expression are involved in seawater acclimation of rainbow trout Oncorhynchus mykiss.

Recent research has shown that nitric oxide (NO) produced by nitric oxide synthases (NOS) is an inhibitor of ion transporter activity and a modulator of epithelial ion transport in fish, but little is known on changes in the NOS/NO system during osmotic stress. We hypothesized that the NOS/NO system responds to salinity changes as an integrated part of the acclimation process. Expression and localization of nos1/Nos1 and nos2/Nos2 were investigated in gill, kidney, and intestine of freshwater (FW)- and seawater (SW)-transferred trout using quantitative PCR, Western blotting, and immunohistochemistry, along with expressional changes of major ion transporters in the gill. The classical branchial ion transporters showed expected expressional changes upon SW transfer, there among a rapid decrease in Slc26a6 mRNA, coding a branchial Cl-/[Formula: see text] exchanger. There was a major downregulation of nos1/ nos2/Nos2 expression in the gill during SW acclimation. A significant decrease in plasma nitrite supported an overall decreased Nos activity and NO production. In the middle intestine, Nos1 was upregulated during SW acclimation, whereas no changes in nos/Nos expression were observed in the posterior intestine and the kidney. Nos1 was localized along the longitudinal axis of the gill filament, beneath smooth muscle fibers of the intestine wall and in blood vessel walls of the kidney. Nos2 was localized within the epithelium adjacent to the gill filament axis and in hematopoietic tissues of the kidney. We conclude that downregulation of branchial NOS is integrated to the SW acclimation process likely to avoid the inhibitory effects of NO on active ion extrusion.

Cortisol regulates nitric oxide synthase in freshwater and seawater acclimated rainbow trout, Oncorhynchus mykiss.

Cortisol and nitric oxide (NO) are regulators of ion transport and metabolic functions in fish. In the gill, they show opposite effects on Na+/K+-ATPase (NKA) activity: cortisol stimulates NKA activity while NO inhibits NKA activity. We hypothesized that cortisol may impact NO production in osmoregulatory tissues by regulating NO synthase (NOS) expression. We evaluated the influence of cortisol treatment on mRNA expression of Nos1 and Nos2 in gill, kidney and middle intestine of both freshwater (FW) and seawater (SW) acclimated rainbow trout and found both tissue- and salinity-dependent effects. Nos2 expression was down-regulated in the gill by cortisol injection in both FW and SW trout. This was substantiated by incubating gill tissue with cortisol ex vivo. Similarly, cortisol injection significantly down-regulated Nos2 expression in kidney of SW fish but not in FW fish. In the middle intestine, Nos2 expression was up-regulated by cortisol injection in FW but unchanged in SW fish. Nos1 expression was up-regulated by cortisol injection in FW kidney and down-regulated in SW kidney, whereas it was unaffected in gill and middle intestine of FW and SW fish. Our data provide the first evidence that cortisol may influence NO production in fish by regulating Nos expression. Indeed, the down-regulation of Nos2 expression by cortisol in the gill may prevent the inhibitory effect of NO on NKA activity thereby furthering the stimulatory effect of cortisol on ion-transport.

Osmotic versus adrenergic control of ion transport by ionocytes of Fundulus heteroclitus in the cold.

In eurythermic vertebrates, acclimation to the cold may produce changes in physiological control systems. We hypothesize that relatively direct osmosensitive control will operate better than adrenergic receptor mediated control of ion transport in cold vs. warm conditions. Fish were acclimated to full strength seawater (SW) at 21°C and 5°C for four weeks, gill samples and blood were taken and opercular epithelia mounted in Ussing style chambers. Short-circuit current (Isc) at 21°C and 5°C (measured at acclimation temperature), was significantly inhibited by the α2-adrenergic agonist clonidine but the ED50 dose was significantly higher in cold conditions (93.8±16.4nM) than in warm epithelia (47.8±8.1nM) and the maximum inhibition was significantly lower in cold (-66.1±2.2%) vs. warm conditions (-85.6±1.3%), indicating lower sensitivity in the cold. ß-Adrenergic responses were unchanged. Hypotonic inhibition of Isc, was higher in warm acclimated (-95%), compared to cold acclimated fish (-75%), while hypertonic stimulations were the same, indicating equal responsiveness to hyperosmotic stimuli. Plasma osmolality was significantly elevated in cold acclimated fish and, by TEM, gill ionocytes from cold acclimated fish had significantly shorter mitochondria. These data are consistent with a shift in these eurythermic animals from complex adrenergic control to relatively simple biomechanical osmotic control of ion secretion in the cold.

Marketing Masked Depression: Physicians, Pharmaceutical Firms, and the Redefinition of Mood Disorders in the 1960s and 1970s.

This article investigates the redefinition of depression that took place in the early 1970s. Well before the introduction of the third edition of the Diagnostic and Statistical Manual of Mental Disorders, this rather rare and severe psychiatric disorder hitherto treated in asylums was transformed into a widespread mild mood disorder to be handled by general practitioners. Basing itself on the archives of the Swiss firm Ciba-Geigy, the article investigates the role of the pharmaceutical industry in organizing this shift, with particular attention paid to research and scientific marketing. By analyzing the interplay between the firm, elite psychiatrists specializing in the study of depression, and general practitioners, the article argues that the collective construction of the market for first-generation antidepressants triggered two realignments: first, it bracketed etiological issues with multiple classifications in favor of a unified symptom-oriented approach to diagnosis and treatment; second, it radically weakened the differentiation between antidepressants, neuroleptics, and tranquilizers. The specific construction of masked depression shows how, in the German-speaking context, issues of ambulatory care such as recognition, classification, and treatment of atypical or mild forms of depression were reshaped to meet commercial as well as professional needs.