Treatment of tapioca starch wastewater by a novel combination of physical and biological processes.

A pilot plant combining dissolved air flotation, anaerobic degradation in an expanded granular sludge bed (EGSB) reactor and aerobic post-treatment in a vertical flow constructed wetland has been used to treat tapioca starch wastewater for more than 2.25 years. It is demonstrated that organic matter (chemical oxygen demand by >98%), nitrogen (Kjeldahl-N by >90%) and cyanide (total cyanide by >99%) can be removed very efficiently under stable operating conditions. The removal efficiency for phosphorus is lower (total-P by 50%). The treatment concept, which includes several sustainable aspects, e.g. production of energy to be used on-site, low operation demands and minimal use of chemicals, could be interesting for small- and middle-sized tapioca processing plants.

Dynamics of sleep-wake cyclicity across the fetal period in sheep (Ovis aries).

All adult mammals examined thus far exhibit sleep bout durations that follow an exponential distribution and wake bout durations that follow a power-law distribution. In altricial rodents such as rats and mice, exponential distributions of sleep bouts are found soon after birth, but the power-law distribution of wake bouts does not emerge until the third postnatal week. Also, both sleep and bouts consolidate across the early postnatal period. It is not known whether similar developmental processes occur in precocial species during the prenatal period. Here we characterize sleep-wake development in a precocial species, the domestic sheep (Ovis aries), from 114 to 148 days gestational age (DGA). Sleep and wake bout durations exhibited exponential distributions throughout the fetal period with some evidence of an emerging exponential-to-power-law transition for wake bouts toward the end of gestation. Both sleep and wake bouts consolidated in an orderly fashion across development and there was little evidence of circadian variation, even in the oldest subjects. These results indicate that similar patterns of sleep-wake organization are found prenatally in a precocial species as are found postnatally in altricial species. Data from more species are needed to fully realize the benefits of a developmental comparative approach for understanding the forces that have shaped the ontogeny and phylogeny of mammalian sleep.

Active medullary control of atonia in week-old rats.

Muscle atonia is a central feature of adult REM sleep which has recently been demonstrated to be a component of sleep in rats as young as 2 days of age (P2). The neural generation of atonia, which depends on mesopontine and medullary structures, is not fully understood in adults and has never been described in infants. In the present experiments we used electrical stimulation in decerebrated pups to identify an inhibitory area within the medial medulla of P7-10 rats. Muscle tone inhibition was consistently found on or near the midline within the ventromedial medulla, dorsal to the inferior olive, in an area that includes the nucleus gigantocellularis, nucleus paramedianus, and raphe obscurus. Chemical infusions in the same region revealed inhibitory responses to quisqualic acid but not to carbachol or corticotropin-releasing factor. Next, extracellular recordings within the medullary inhibitory area revealed neurons with atonia-on profiles; tone-on neurons were also found, typically at more lateral sites. Finally, in non-decerebrated pups, chemical lesions within the inhibitory area resulted in significant reductions in atonia durations, as well as decoupling of atonia from a second component of infant sleep, myoclonic twitching; specifically, twitches occasionally occurred during periods of high muscle tone, a condition reminiscent of "REM without atonia" as described in adults. In summary, we document the existence of an area within the ventromedial medulla of infant rats that (i) causes atonia when stimulated; (ii) contains units that exhibit atonia-related discharge profiles during sleep-wake cycling; and (iii) when lesioned, results in the partial loss of atonia and decoupling of the components of sleep. All together, these findings demonstrate that muscle atonia is actively regulated very early in ontogeny.

Hypothalamic contribution to sleep-wake cycle development.

Infant mammals cycle rapidly between sleep and wakefulness and only gradually does a more consolidated sleep pattern develop. The neural substrates responsible for this consolidation are unknown. To establish a reliable measure of sleep-wake cyclicity in infant rats, nuchal muscle tone was measured in 2-, 5-, and 8-day-old rats, as were motor behaviors associated with sleep (i.e. myoclonic twitching) and wakefulness (e.g. kicking, stretching). Sleep-wake cycles of 2-day-old rats were characterized by short periods of muscle atonia followed by equally short periods of high tone. In 8-day-olds, sleep periods lengthened significantly and disproportionately in relation to awake periods. Next, locus coeruleus (LC) lesions in 8-day-olds resulted in rapid sleep-wake cycling similar to that exhibited by 2-day-olds; in addition, LC lesions had no effect on the duration of awake periods. Finally, transections caudal, but not rostral, to the anterior hypothalamus also reinstated rapid cycling in 8-day-olds, again without affecting the duration of awake periods. This last finding implicates neural structures within the anterior hypothalamus (e.g. ventrolateral preoptic area) in the modulation of sleep-wake cyclicity. The temporal coherence of atonia and myoclonic twitching was not disrupted by any of the manipulations. These results suggest the presence of a bistable mesopontine circuit governing rapid sleep-wake cycling that does not include the LC and that comes increasingly under hypothalamic control during the first postnatal week. This circuit may represent a basic building block with which other sleep components become integrated during ontogeny.

Familial leiomyomatosis: a review and discussion of pathogenesis.

Multiple cutaneous leiomyomas of pilar origin have long been recognized to have an autosomal dominant inheritance. While the skin tumors are relatively uncommon and benign, women of affected families often develop uterine fibroids with associated infertility, pain and bleeding. In addition, a subset of these families harbors a predisposition to papillary renal cell carcinoma. Germline mutations in a recently identified classical tumor suppressor gene encoding fumarate hydratase are observed in these individuals. Appropriate screening measures for associated disorders are mandatory.

Neural and hormonal control of arterial pressure during cold exposure in unanesthetized week-old rats.

Infant rats respond to cold exposure with increased heat production by brown adipose tissue (BAT). BAT thermogenesis increases steadily with increasing cold exposure, but a point occurs at which thermogenesis can increase no further, resulting in cold-induced bradycardia. Previous work has shown that mean arterial pressure (MAP) is maintained even when cardiac rate decreases as much as 50% from baseline values. We examined the neural and hormonal contributions to peripheral resistance during cold exposure after pups were injected subcutaneously with vehicle, an alpha1-adrenoceptor antagonist (prazosin; 0.5 mg/kg), an ANG II receptor antagonist (losartan; 1 mg/kg), a vasopressin receptor antagonist (Manning compound; 0.5 mg/kg), or simultaneous administration of all three antagonists (triple block). Interscapular temperature, oxygen consumption, cardiac rate, and arterial pressure were monitored as air temperature was sequentially decreased from thermoneutral (i.e., 35 degrees C) to 29, 23, and 17 degrees C. Only pups in the triple block condition exhibited significant decreases in MAP with cooling, even though all pups exhibited substantial decreases in cardiac rate. A followup study suggested that blockade of all three systems was more effective than blockade of any two systems. Finally, at 17 degrees C, ultrasonic vocalizations were accompanied by significant increases in MAP, replicating a previous finding and supporting the hypothesis that the vocalization is the acoustic by-product of the abdominal compression reaction, a maneuver that helps to maintain venous return during cardiovascular challenge.

Competition and cooperation among huddling infant rats.

Huddling is expressed by infant rats and continues to be an important behavior throughout adulthood. As a form of behavioral thermoregulation, huddling is thought to play an essential role in compensating for inadequate physiological thermoregulation early in development. Infant rats, however, are capable of heat production shortly after birth using brown adipose tissue (BAT) and exhibit thermogenesis in the huddle, suggesting that huddling does not obviate the need for endothermy during cold exposure. In the present experiment, 4-pup huddles of infant rats (2- or 8-day-olds) were exposed to two subthermoneutral temperatures, and BAT thermogenesis was inhibited in 0, 2, or 4 of the rats in each huddle. Inhibition of BAT thermogenesis compromised the pups' ability to maintain huddle temperature, but surprisingly did not result in enhanced huddling at either age. These results suggest that effective huddling during cold exposure requires the thermal resources provided by endothermy. Furthermore, the heat provided by BAT appears to shape behavioral interactions in the huddle during development.

Early life stress and disease among offspring and siblings of individuals with type 1 diabetes mellitus.

Major life events, recent life stressors, and childhood diseases were examined among children and adolescents who were offspring, siblings, or other relatives of persons with type 1 diabetes mellitus (DM). All youth were recruited as part of a multi-site nationwide trial on the prevention of type 1 DM; parents of 347 children (4 to 18 yr) completed measures that asked about children's life events, recent stressors, and childhood illnesses. Analyses compared age groups (young child, preadolescent, adolescent) and relative type (offspring, sibling, other relative). Findings revealed offspring and siblings did not differ from "other relatives" in terms of life events, recent life stress, and disease/illness variables. However, siblings were reported to have fewer major life events and fewer life stressors in the past 12 months than offspring; siblings also had fewer infectious diseases during the first two years of life compared to offspring. Few age-related differences were found. Overall, results suggest that offspring and siblings of persons with type 1 DM are not at a disadvantage in terms of early life stress or disease in comparison to youth who have other family members with diabetes. However, siblings may have some advantages relative to children who are offspring. The mechanisms underlying these relationships require further elucidation and study.

Do infant rats cry?

In the current revival of interest in the emotional and mental lives of animals, many investigators have focused attention on mammalian infants that emit distress vocalizations when separated from the home environment. Perhaps the most intensively studied distress vocalization is the ultrasonic vocalization of infant rats. Since its discovery, this vocalization has been interpreted both as a communicatory signal for the elicitation of maternal retrieval and as the manifestation of emotional distress. In contrast, the authors examined the cardiovascular causes and consequences of the vocalization, and on the basis of this work, they hypothesized that the vocalization is the acoustic by-product of the abdominal compression reaction (ACR), a maneuver that results in increased venous return to the heart. Therefore, the vocalization may be analogous to a sneeze, serving a physiological function while incidentally producing sound.

Mesopontine contribution to the expression of active 'twitch' sleep in decerebrate week-old rats.

Myoclonic twitching is a ubiquitous feature of infant behavior that has been used as an index of active sleep. Although the active sleep of infants differs in some ways from the REM sleep of adults, their marked similarities have led many to view them them as homologous behavioral states. Recently, however, this view has been challenged. One avenue for resolving this issue entails examination of the neural substrates of active sleep. If the neural substrates of active sleep were found to be similar to those of REM sleep, then this would support the view that the two states are homologous. Therefore, in the present study, decerebrations were performed in the pons and midbrain to determine whether the mesopontine region is important for the expression of active sleep in infants, just as it is for the expression of REM sleep in adults. It was found that, in comparison to controls, caudal pontine decerebrations reduced myoclonic twitching by 76%, rostral pontine decerebrations reduced twitching by 40%, and midbrain transections had no significant effect on twitching. Moreover, analysis of the temporal organization of twitching indicated that pontine decerebrations predominantly affected high-frequency twitching while leaving unaffected the low-frequency twitching that is thought to be contributed by local spinal circuits at this age. These results indicate that the mesopontine region plays a central role in the expression of active sleep in infant rats.

A comparative analysis of huddling in infant Norway rats and Syrian golden hamsters: does endothermy modulate behavior?

In infant rats, huddling improves surface-to-volume ratios and provides metabolic savings during cold exposure. It is unclear, however, whether endothermy is also a necessary component of huddling. In the present experiment, huddles composed of infant Norway rats (2- or 8-day-olds), which produce heat endogenously, or Syrian golden hamsters (8-day-olds), which do not produce heat endogenously, were exposed to decreases in air temperature. Behavioral and physiological responses were monitored throughout the test. Rats, especially at 8 days of age, were better able to thermoregulate using huddling than hamsters, due in part to endogenous heat production. Furthermore, 8-day-old rats exhibited behavioral responses that promote heat retention, suggesting that both physiological and behavioral mechanisms contribute to effective thermoregulation during huddling in the cold.

Cardiovascular mediation of clonidine-induced ultrasound production in infant rats.

In infant rats, administration of the alpha2 adrenoceptor agonist clonidine simultaneously evokes ultrasound production and bradycardia. In this study the authors examined in 8-day-old rats whether these 2 responses to clonidine are causally related. In Experiment 1 pups were pretreated with saline or prenalterol (0.1 or 1.0 mg/kg), a beta1 adrenoceptor agonist that increases cardiac rate, followed by administration of clonidine (1.0 mg/kg). Prenalterol pretreatment suppressed clonidine-induced ultrasound production at both doses. Prenalterol also increased skin temperature, however, suggesting that suppression of ultrasound was modulated in part by increased body temperature. Consistent with this suggestion, in Experiment 2 mild hyperthermia significantly inhibited clonidine-induced ultrasound production. Finally, in Experiment 3 the authors found that the pretreatments used in Experiments 1 and 2 prevent or dampen the effects of clonidine on cardiac rate. These results suggest that clonidine's effect on ultrasound production is mediated by its effects on the cardiovascular system.

Spontaneous motor activity in fetal and infant rats is organized into discrete multilimb bouts.

Spontaneous motor activity (SMA) is a ubiquitous feature of fetal and infant behavior. Although SMA appears random, successive limb movements often occur in bouts. Bout organization was evident at all ages in fetal (embryonic day [E] 17-21) and infant (postnatal day [P] 1-9) rats, with nearly all bouts comprising 1-4 movements of different limbs. A computational model of SMA, including spontaneous activity of spinal motor neurons, intrasegmental and intersegmental interactions, recurrent inhibition, and descending influences, produced bouts with the same structure as that observed in perinatal rats. Consistent with the model, bouts were not eliminated on E20 after cervical spinal transection, suggesting that the brain is not necessary to produce bout organization. These investigations provide a foundation for understanding the contributions of SMA to neuromuscular and motor development.

A developmental analysis of clonidine's effects on cardiac rate and ultrasound production in infant rats.

Under controlled conditions, infant rats emit ultrasonic vocalizations during extreme cold exposure and after administration of the alpha(2) adrenoceptor agonist, clonidine. Previous investigations have determined that, in response to clonidine, ultrasound production increases through the 2nd-week postpartum and decreases thereafter. Given that sympathetic neural dominance exhibits a similar developmental pattern, and given that clonidine induces sympathetic withdrawal and bradycardia, we hypothesized that clonidine's developmental effects on cardiac rate and ultrasound production would mirror each other. Therefore, in the present experiment, the effects of clonidine administration (0.5 mg/kg) on cardiac rate and ultrasound production were examined in 2-, 8-, 15-, and 20-day-old rats. Age-related changes in ultrasound production corresponded with changes in cardiovascular variables, including baseline cardiac rate and clonidine-induced bradycardia. This experiment is discussed with regard to the hypothesis that ultrasound production is the acoustic by-product of a physiological maneuver that compensates for clonidine's detrimental effects on cardiovascular function.

Distress vocalizations in infant rats: what's all the fuss about?

Ultrasonic vocalizations emitted by infant rodents are typically characterized as cries of distress. There are two contexts that are known to reliably elicit ultrasound production: extreme cold exposure and administration of clonidine, an alpha 2 adrenoceptor agonist. Noting that these two contexts both entail pronounced decreases in cardiac rate, we have hypothesized that the vocalizations are acoustic by-products of a physiological maneuver, the abdominal compression reaction (ACR), that increases venous return to the heart when return is compromised. As a critical test of this hypothesis, we measured venous pressure near the right atrium in 15-day-old rats after clonidine administration. Consistent with the ACR hypothesis, emission of ultrasound was accompanied by large and reliable increases in venous pressure and, therefore, venous return. These results provide strong, direct support for the ACR hypothesis and, by doing so, underscore the potential pitfalls of anthropomorphic interpretations of the vocalizations of infant rats.

Geotaxis in 2-week-old Norway rats (Rattus norvegicus): A reevaluation.

In 1926, Crozier and Pincus first reported that 2-week-old rats placed head-down on an inclined plane orient in a head-up direction; this response is called negative geotaxis. In Experiment 1, we replicated this finding by testing 12- to 14-day-old rats on an inclined plane covered with wire mesh. Pups oriented in a head-up direction and avoided the head-down direction at inclines of 45 degrees but not 30 degrees. Because pups in Experiment 1 appeared to grasp the wire mesh with their claws, pups in Experiment 2 were now tested on a smooth but high-friction substrate. At inclines of 30 degrees, 35 degrees, and 40 degrees, pups did not exhibit significant tendencies to orient in a head-up direction or avoid a head-down direction. Finally, in Experiment 3, the effect of substrate on geotaxis was tested further by comparing pups' behaviors at 40 degrees with the inclined plane covered with either wire mesh or the high-friction substrate. Pups' orientation behaviors differed on the two substrates. Taken together, these data suggest that testing substrate affects the orientation behaviors of young rats and raise questions about the plausibility of applying the concept of geotaxis to young mammals, at least when tested on an inclined plane.

Thermoregulatory and cardiac responses of infant spontaneously hypertensive and Wistar-Kyoto rats to cold exposure.

Cardiovascular function during cold exposure is dependent on effective thermoregulation. This dependence is particularly apparent in infants. For example, we have previously demonstrated that in infant rats during cold exposure, cardiac rate is directly related to their ability to produce heat endogenously. The primary source of endogenous heat production for infant rats is brown adipose tissue (BAT). Because of the dependence of cardiac rate on effective thermoregulation in the cold and because hypertension in spontaneously hypertensive rats (SHR) is influenced by the preweanling environment, in this study we examined the thermoregulatory and cardiac rate responses of infant SHR and Wistar-Kyoto rats (WKY) to varying levels of cold exposure. In experiment 1, 7- to 8-day-old SHR and WKY were acclimated at a thermoneutral air temperature (35 degrees C) and then exposed to successive decreases in ambient temperature (30.5 degrees C, 26.5 degrees C, 23 degrees C, and 17 degrees C) while thermal and metabolic measures were recorded. Although both strains increased BAT thermogenesis and oxygen consumption in response to cold exposure, SHR cooled more than WKY and exhibited lower levels of oxygen consumption at the lowest air temperatures. Experiment 2 was identical to experiment 1 except that cardiac rate was also measured. Again, SHR exhibited substantial thermoregulatory deficits compared with WKY; in addition, they were less able than WKY to maintain cardiac rate at the 2 lowest air temperatures tested. Finally, in experiment 3, infant SHR exhibited diminished BAT thermogenesis in response to a range of doses of a selective beta3-adrenoceptor agonist. We hypothesize that long-term thermoregulatory deficits during the early postnatal period influence cardiovascular function and contribute to the development of hypertension in SHR.