Berkeley Open Extended Reality Recordings 2023 (BOXRR-23): 4.7 Million Motion Capture Recordings from 105,000 XR Users.

Extended reality (XR) devices such as the Meta Quest and Apple Vision Pro have seen a recent surge in attention, with motion tracking "telemetry" data lying at the core of nearly all XR and metaverse experiences. Researchers are just beginning to understand the implications of this data for security, privacy, usability, and more, but currently lack large-scale human motion datasets to study. The BOXRR-23 dataset contains 4,717,215 motion capture recordings, voluntarily submitted by 105,852 XR device users from over 50 countries. BOXRR-23 is over 200 times larger than the largest existing motion capture research dataset and uses a new, highly efficient and purpose-built XR Open Recording (XROR) file format.

View-Dependent Adaptive Cloth Simulation with Buckling Compensation.

This paper describes a method for view-dependent cloth simulation using dynamically adaptive mesh refinement and coarsening. Given a prescribed camera motion, the method adjusts the criteria controlling refinement to account for visibility and apparent size in the camera's view. Objectionable dynamic artifacts are avoided by anticipative refinement and smoothed coarsening, while locking in extremely coarsened regions is inhibited by modifying the material model to compensate for unresolved sub-element buckling. This approach preserves the appearance of detailed cloth throughout the animation while avoiding the wasted effort of simulating details that would not be discernible to the viewer. The computational savings realized by this method increase as scene complexity grows. The approach produces a 2× speed-up for a single character and more than 4× for a small group as compared to view-independent adaptive simulations, and respectively 5× and 9× speed-ups as compared to non-adaptive simulations.

Chronic prenatal ethanol exposure alters expression of central and peripheral insulin signaling molecules in adult guinea pig offspring.

Maternal ethanol consumption during pregnancy can produce a range of teratogenic outcomes in offspring. The mechanism of ethanol teratogenicity is multi-faceted, but may involve alterations in insulin and insulin-like growth factor (IGF) signaling pathways. These pathways are not only important for metabolism, but are also critically involved in neuronal survival and plasticity, and they can be altered by chronic prenatal ethanol exposure (CPEE). The objective of this study was to test the hypothesis that CPEE alters expression of insulin and IGF signaling molecules in the prefrontal cortex and liver of adult guinea pig offspring. Pregnant Dunkin-Hartley-strain guinea pigs received ethanol (4 g/kg maternal body weight/day) or isocaloric-sucrose/pair-feeding (nutritional control) throughout gestation. Fasting blood glucose concentration was measured in male and female offspring at postnatal day 150-200, followed by euthanasia, collection of prefrontal cortex and liver, and RNA extraction. IGF-1, IGF-1 receptor (IGF-1R), IGF-2, IGF-2 receptor (IGF-2R), insulin receptor substrate (IRS)-1, IRS-2, and insulin receptor (INSR) mRNA expression levels were measured in tissues using quantitative real-time PCR. The mean maternal blood ethanol concentration was 281 ± 15 mg/dL at 1 h after the second divided dose of ethanol on GD 57. CPEE resulted in increased liver weight in adult offspring, but produced no difference in fasting blood glucose concentration compared with nutritional control. In the liver, CPEE decreased mRNA expression of IGF-1, IGF-1R, and IGF-2, and increased IRS-2 mRNA expression in male offspring only compared with nutritional control. Female CPEE offspring had decreased INSR hepatic mRNA expression compared with male CPEE offspring. In the prefrontal cortex, IRS-2 mRNA expression was increased in CPEE offspring compared with nutritional control. The data demonstrate that CPEE alters both central and peripheral expression of insulin and IGF signaling molecules at the mRNA level, which may be related to metabolic dysregulation in adult offspring. Furthermore, altered insulin and IGF signaling may be a mechanism of ethanol neurobehavioral teratogenicity.

Chronic ethanol exposure increases the non-dominant glucocorticoid, corticosterone, in the near-term pregnant guinea pig.

Maternal-fetal signaling is critical for optimal fetal development and postnatal outcomes. Chronic ethanol exposure alters programming of the fetal hypothalamic-pituitary-adrenal (HPA) axis, resulting in a myriad of neurochemical and behavioral alterations in postnatal life. Based on a recent study which showed that human intra-partum fetal stress increased fetal secretion of corticosterone, the non-dominant glucocorticoid, this investigation tested the hypothesis that an established model of HPA axis programming, chronic maternal ethanol administration to the pregnant guinea pig, would result in preferential elevation of corticosterone, which is also the non-dominant glucocorticoid. Starting on gestational day (GD) 2, guinea pigs received oral administration of ethanol (4 g/kg maternal body weight/day) or isocaloric-sucrose/pair-feeding. Each treatment was administered daily and continued until GD 45, 55, or 65 (approximately 3 days pre-term), when pregnant animals were euthanized and fetuses delivered by Caesarean section. Maternal and fetal plasma samples were collected. After sample preparation (protein precipitation and C-18 solid phase extraction), plasma cortisol and corticosterone concentrations were determined simultaneously by liquid chromatography coupled to tandem mass spectrometry. As predicted, chronic ethanol exposure increased both fetal and maternal plasma corticosterone concentration in late gestation. In contrast, plasma cortisol did not differ across maternal treatments in maternal or fetal samples. The plasma concentration of both maternal glucocorticoids increased with gestational age. Thus, corticosterone, the non-dominant glucocorticoid, but not cortisol, was elevated by chronic ethanol exposure, which may have effects on HPA function in later life.

Maternal alcohol consumption in pregnancy enhances arterial stiffness and alters vasodilator function that varies between vascular beds in fetal sheep.

While the impact of alcohol consumption by pregnant women on fetal neurodevelopment has received much attention, the effects on the cardiovascular system are not well understood. We hypothesised that repeated exposure to alcohol (ethanol) in utero would alter fetal arterial reactivity and wall stiffness, key mechanisms leading to cardiovascular disease in adulthood. Ethanol (0.75 g (kg body weight)(-1)) was infused intravenously into ewes over 1 h daily for 39 days in late pregnancy (days 95-133 of pregnancy, term ∼147 days). Maternal and fetal plasma ethanol concentrations at the end of the hour were ∼115 mg dl(-1), and then declined to apparent zero over 8 h. At necropsy (day 134), fetal body weight and fetal brain-body weight ratio were not affected by alcohol infusion. Small arteries (250-300 µm outside diameter) from coronary, renal, mesenteric, femoral (psoas) and cerebral beds were isolated. Endothelium-dependent vasodilatation sensitivity was reduced 10-fold in coronary resistance arteries, associated with a reduction in endothelial nitric oxide synthase mRNA (P = 0.008). Conversely, vasodilatation sensitivity was enhanced 10-fold in mesenteric and renal resistance arteries. Arterial stiffness was markedly increased (P = 0.0001) in all five vascular beds associated with an increase in elastic modulus and, in cerebral vessels, with an increase in collagen Iα mRNA. Thus, we show for the first time that fetal arteries undergo marked and regionally variable adaptations as a consequence of repeated alcohol exposure. These alcohol-induced vascular effects occurred in the apparent absence of fetal physical abnormalities or fetal growth restriction.

In vitro Activation of heme oxygenase-2 by menadione and its analogs.

BACKGROUND: Previously, we reported that menadione activated rat, native heme oxygenase-2 (HO-2) and human recombinant heme oxygenase-2 selectively; it did not activate spleen, microsomal heme oxygenase-1. The purpose of this study was to explore some structure-activity relationships of this activation and the idea that redox properties may be an important aspect of menadione efficacy. METHODS: Heme oxygenase activity was determined in vitro using rat spleen and brain microsomes as the sources of heme oxygenase-1 and -2, respectively, as well as recombinant, human heme oxygenase-2. RESULTS: Menadione analogs with bulky aliphatic groups at position-3, namely vitamins K1 and K2, were not able to activate HO-2. In contrast, several compounds with similar bulky but less lipophilic moieties at position-2 (and -3) were able to activate HO-2 many fold; these compounds included polar, rigid, furan-containing naphthoquinones, furan-benzoxazine naphthoquinones, 2-(aminophenylphenyl)-3-piperidin-1-yl naphthoquinones. To explore the idea that redox properties might be involved in menadione efficacy, we tested analogs such as 1,4-dimethoxy-2-methylnaphthalene, pentafluoromenadione, monohalogenated naphthoquinones, α-tetralone and 1,4-naphthoquinone. All of these compounds were inactive except for 1,4-naphthoquinone. Menadione activated full-length recombinant human heme oxygenase-2 (FL-hHO-2) as effectively as rat brain enzyme, but it did not activate rat spleen heme oxygenase. CONCLUSIONS: These observations are consistent with the idea that naphthoquinones such as menadione bind to a receptor in HO-2 and activate the enzyme through a mechanism that may involve redox properties.

Cytotoxic interaction between amiodarone and desethylamiodarone in human peripheral lung epithelial cells.

The potent and efficacious anti-dysrhythmic agent amiodarone (AM) can cause potentially life-threatening lung damage (amiodarone-induced pulmonary toxicity; AIPT), which is characterized by cell death in the lungs, followed by inflammation and fibrosis. AM's major metabolite, desethylamiodarone (DEA), has a greater toxic potency than AM and it has been suggested that DEA may act synergistically with AM to cause lung toxicity. The objective of this study was to determine the type of cytotoxic interaction between AM and DEA in HPL1A human peripheral lung epithelial cells. Cytotoxicity was measured by lactate dehydrogenase release. AM and DEA caused concentration-dependent cytotoxicity in HPL1A cells. The concentration of drug causing 50% cell death (LC50) and the Hill slope factor, which represents steepness of the concentration-cell death curve, were significantly different between AM and DEA (12.4µM and 1.98; 5.07µM and 5.43, for AM and DEA, respectively) indicating that they may induce cytotoxicity through different mechanisms. A combined concentration of 7.13µM AM plus DEA, equivalent to 41% of each compound's individual LC50 value, resulted in 50% cell death. Isobolographic analysis revealed this effect to be additive, although the combined concentrations were only slightly higher than the concentrations that defined the threshold of synergy (threshold of synergy=4.21±1.98µM AM plus 1.73±1.05µM DEA; experimental data point=5.06±0.47µM AM plus 2.07±0.47µM DEA). The cytotoxic interaction between AM and DEA may be clinically relevant in the development of AIPT.

Alcohol exposure during late ovine gestation alters fetal liver iron homeostasis without apparent dysmorphology.

High levels of alcohol (ethanol) exposure during fetal life can affect liver development and can increase susceptibility to infection after birth. Our aim was to determine the effects of a moderate level of ethanol exposure in late gestation on the morphology, iron status, and inflammatory status of the ovine fetal liver. Pregnant ewes were chronically catheterized at 91 days of gestation (DG; term ~145 DG) for daily intravenous infusion of ethanol (0.75 g/kg maternal body wt; n = 8) or saline (n = 7) over 1 h from 95 to 133 DG. At necropsy (134 DG), fetal livers were collected for analysis. Liver weight, general liver morphology, hepatic cell proliferation and apoptosis, perivascular collagen deposition, and interleukin (IL)-1ß, IL-6, or IL-8 mRNA levels were not different between groups. However, ethanol exposure led to significant decreases in hepatic content of ferric iron and gene expression of the iron-regulating hormone hepcidin and tumor necrosis factor (TNF)-α (all P < 0.05). In the placenta, there was no difference in transferrin receptor, divalent metal transporter 1, and ferritin mRNA levels; however, ferroportin mRNA levels were increased in ethanol-exposed animals (P < 0.05), and ferroportin protein tended to be increased (P = 0.054). Plasma iron concentration was not different between control and ethanol-exposed groups; control fetuses had significantly higher iron concentrations than their mothers, whereas maternal and fetal iron concentrations were similar in ethanol-exposed animals. We conclude that daily ethanol exposure during the third-trimester-equivalent in sheep does not alter fetal liver morphology; however, decreased fetal liver ferric iron content and altered hepcidin and ferroportin gene expression indicate that iron homeostasis is altered.

Meconium fatty acid ethyl esters as biomarkers of late gestational ethanol exposure and indicator of ethanol-induced multi-organ injury in fetal sheep.

BACKGROUND: Meconium fatty acid ethyl esters (FAEE) constitute a biomarker of heavy fetal ethanol exposure. Our objective was to measure meconium FAEE in fetal sheep following daily, relatively moderate-dose ethanol exposure in late gestation, and to evaluate their utility in identifying fetal organ-system injury. METHODS: Pregnant ewes received ethanol (0.75 g/kg; n = 14) or saline (n = 8) via 1-h i.v. infusion daily during the third trimester equivalent, while additional pregnant sheep served as untreated controls (n = 6). The daily ethanol regimen produced similar maximal maternal and fetal plasma ethanol concentrations of 0.11-0.12 g/dL. Ewes and fetuses were euthanized shortly before term, and meconium was collected and analyzed for FAEE (ethyl palmitate, stearate, linoleate, and oleate). RESULTS: Meconium total FAEE concentration was significantly higher in ethanol-exposed fetuses compared with controls, and a positive cut-off of 0.0285 nmol total FAEE/g meconium had 93.3% sensitivity and specificity for detecting fetal ethanol exposure. When the studied animals (ethanol-exposed and controls) were classified according to meconium FAEE concentration, FAEE-positive and FAEE-negative groups frequently differed with respect to previously examined pathological endpoints, including nephron endowment, lung collagen deposition, cardiomyocyte maturation, and tropoelastin gene expression in cerebral vessels. Furthermore, in all studied animals as a group (ethanol-exposed and controls combined), meconium FAEE concentration was correlated with many of these pathological endpoints in fetal organs. CONCLUSIONS: We conclude that, in fetal sheep, meconium FAEE could serve as a biomarker of daily ethanol exposure in late gestation and could identify fetuses with subtle ethanol-induced toxic effects in various organs. This study illustrates the potential for using meconium FAEE to identify neonates at risk for dysfunction of major organs following in-utero ethanol exposure that does not result in overt physical signs of ethanol teratogenicity.

Sensitivity of modified Biel-maze task, compared with Y-maze task, to measure spatial learning and memory deficits of ethanol teratogenicity in the guinea pig.

Ethanol consumption during pregnancy can produce a variety of teratogenic effects in offspring, termed Fetal Alcohol Spectrum Disorders (FASD). The most debilitating and permanent consequence of chronic prenatal ethanol exposure (CPEE) is neurobehavioral teratogenicity, which often manifests as cognitive and behavioral impairments, including deficits in spatial learning and memory. This study tested the hypothesis that a modified dry-land version of the multi-choice Biel-maze task is more sensitive than the rewarded-alternation Y-maze task for the determination of spatial learning and memory deficits of ethanol teratogenicity. Pregnant guinea pigs received ethanol (4 g/kg maternal body weight/day) or isocaloric-sucrose/pair-feeding (control) for 5days/week throughout gestation. CPEE resulted in ethanol neurobehavioral teratogenicity in offspring, as demonstrated by increased spontaneous locomotor activity at postnatal day (PD) 10 and decreased brain weight at euthanasia (PD 150-200). On PD 21, offspring were randomly assigned to one of two tasks to assess spatial learning and memory performance: a dry-land version of the Biel maze or a rewarded-alternation Y-maze. Animals were habituated to the environment of their assigned task and performance of each CPEE or control offspring was measured. In the modified Biel maze, CPEE and control offspring were not different for percent completed trials or time to complete a trial. However, CPEE offspring made more errors (reversals and entering dead ends) in the Biel maze, demonstrating impaired spatial learning and memory. In contrast, CPEE offspring did not have impaired performance of the rewarded-alternation Y-maze task. Therefore, the modified dry-land version of the Biel-maze task, which measures cognitive performance using a complex multi-choice design, is more sensitive in demonstrating CPEE-induced spatial learning and memory deficits compared with a simple, rewarded-alternation Y-maze task.

Maternal ethanol consumption by pregnant guinea pigs causes neurobehavioral deficits and increases ethanol preference in offspring.

The objective of this study was to test the hypothesis that prenatal exposure to ethanol, through maternal consumption of an aqueous ethanol solution, induces neurobehavioral deficits and increases ethanol preference in offspring. Pregnant Dunkin-Hartley-strain guinea pigs were given 24-h access to an aqueous ethanol solution (5%, v/v) sweetened with sucralose (1 g/l), or water sweetened with sucralose (1 g/l), throughout gestation. Spontaneous locomotor activity was measured in the offspring on postnatal day (PD) 10. The offspring underwent either ethanol preference testing using a two-bottle-choice paradigm beginning on PD 40 or Morris water maze testing using a hidden moving platform design beginning on PD 60. Maternal consumption of a 5% (v/v) ethanol solution (average daily dose of 2.3±0.1 g of ethanol/kg maternal body weight; range: 1.8-2.8 g/kg) decreased offspring birth weight, increased spontaneous locomotor activity, and increased preference for an aqueous ethanol solution. In the Morris water maze test, sucralose-exposed offspring decreased escape latency on the second day of testing, whereas the ethanol-exposed offspring showed no improvement. These data demonstrate that moderate maternal consumption of ethanol produces hyperactivity, enhances ethanol preference, and impairs learning and memory in guinea pig offspring.

Selective activation of heme oxygenase-2 by menadione.

While substantial progress has been made in elucidating the roles of heme oxygenases-1 (HO-1) and -2 (HO-2) in mammals, our understanding of the functions of these enzymes in health and disease is still incomplete. A significant amount of our knowledge has been garnered through the use of nonselective inhibitors of HOs, and our laboratory has recently described more selective inhibitors for HO-1. In addition, our appreciation of HO-1 has benefitted from the availability of tools for increasing its activity through enzyme induction. By comparison, there is a paucity of information about HO-2 activation, with only a few reports appearing in the literature. This communication describes our observations of the up to 30-fold increase in the in-vitro activation of HO-2 by menadione. This activation was due to an increase in Vmax and was selective, in that menadione did not increase HO-1 activity.

Chronic ethanol exposure and folic acid supplementation: fetal growth and folate status in the maternal and fetal guinea pig.

Chronic ethanol exposure (CEE) can produce developmental abnormalities in the CNS of the embryo and developing fetus. Folic acid (FA) is an important nutrient during pregnancy and low folate status exacerbates ethanol-induced teratogenicity. This study tested the hypotheses that (1) CEE depletes folate stores in the mother and fetus; and (2) maternal FA supplementation maintains folate stores. CEE decreased fetal body, brain, hippocampus weights, and brain to body weight ratio but not hippocampus to body weight ratio. These effects of CEE were not mitigated by maternal FA administration. The FA regimen prevented the CEE-induced decrease of term fetal liver folate. However, it did not affect maternal liver folate or fetal RBC folate at term, and did not mitigate the nutritional deficit-induced decrease of term fetal hippocampus folate. This study suggests that maternal FA supplementation may have differential effects on folate status in the mother and the fetus.

Mechanisms of amiodarone and desethylamiodarone cytotoxicity in nontransformed human peripheral lung epithelial cells.

Amiodarone (AM) is a potent antidysrhythmic agent that can cause potentially life-threatening pulmonary fibrosis, and N-desethylamiodarone (DEA), an AM metabolite, may contribute to AM toxicity. Apoptotic cell death in nontransformed human peripheral lung epithelial 1A (HPL1A) cells was assessed by annexin V-fluorescein isothiocyanate (ann-V) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), and necrotic cell death was assessed by propidium iodide (PI) staining. The percentage of cells that were PI-positive increased more than six times with 20 µM AM and approximately doubled with 3.5 µM DEA, relative to control. The percentage of cells that were ann-V-positive decreased by more than 80% after 24-h exposure to 10 µM AM but more than doubled after 24-h incubation with 3.5 µM DEA. Incubation for 24 h with 5.0 µM DEA increased the percentage of cells that were TUNEL-positive more than six times. Incubation with AM (2.5 µM) or DEA (1-2 µM) for 24 h did not significantly alter angiotensinogen mRNA levels. Furthermore, angiotensin II (100 pM-1 µM) alone or in combination with AM or DEA did not alter cytotoxicity, and pretreatment with the angiotensin-converting enzyme inhibitor and antioxidant captopril (3-6 µM) did not protect against AM or DEA cytotoxicity. In conclusion, AM activates primarily necrotic pathways, whereas DEA activates both necrotic and apoptotic pathways, and the renin-angiotensin system does not seem to be involved in AM or DEA cytotoxicity in HPL1A cells.

Recombinant truncated and microsomal heme oxygenase-1 and -2: differential sensitivity to inhibitors.

Recombinant truncated forms of heme oxygenase-1 and -2 (HO-1 and HO-2) were compared with their crude microsomal counterparts from brain and spleen tissue of adult male rats with respect to their inhibition by azole-based, nonporphyrin HO inhibitors. The drugs tested were an imidazole-alcohol, an imidazole-dioxolane, and a triazole-ketone. Both the recombinant and crude forms of HO-2 were similarly inhibited by the 3 drugs. The crude microsomal spleen form of HO-1 was more susceptible to inhibition than was the truncated recombinant form. This difference is attributed to the extra amino acids in the full-length enzyme. These observations may be relevant in the design of drugs as inhibitors of HO and other membrane proteins.

Using Blur to Affect Perceived Distance and Size.

We present a probabilistic model of how viewers may use defocus blur in conjunction with other pictorial cues to estimate the absolute distances to objects in a scene. Our model explains how the pattern of blur in an image together with relative depth cues indicates the apparent scale of the image's contents. From the model, we develop a semiautomated algorithm that applies blur to a sharply rendered image and thereby changes the apparent distance and scale of the scene's contents. To examine the correspondence between the model/algorithm and actual viewer experience, we conducted an experiment with human viewers and compared their estimates of absolute distance to the model's predictions. We did this for images with geometrically correct blur due to defocus and for images with commonly used approximations to the correct blur. The agreement between the experimental data and model predictions was excellent. The model predicts that some approximations should work well and that others should not. Human viewers responded to the various types of blur in much the way the model predicts. The model and algorithm allow one to manipulate blur precisely and to achieve the desired perceived scale efficiently.

Differential effects of chronic ethanol exposure on cytochrome P450 2E1 and the hypothalamic-pituitary-adrenal axis in the maternal-fetal unit of the guinea pig.

BACKGROUND: Ethanol neurobehavioural teratogenicity is a leading cause of developmental mental deficiency, in which the hippocampus is a target site of injury. The multi-faceted mechanism of ethanol teratogenicity is not completely understood. This study tested the hypothesis that chronic ethanol exposure (CEE), via chronic maternal ethanol administration, increases cytochrome P450 2E1 (CYP2E1) expression and alters hypothalamic-pituitary-adrenal (HPA) axis activity in the maternal-fetal unit during the third-trimester-equivalent of gestation. METHODS: Pregnant Dunkin-Hartley-strain guinea pigs received daily oral administration of ethanol (4 g ethanol/kg maternal body weight) or isocaloric-sucrose/pair-feeding (control) throughout gestation (term, about gestational day (GD) 68). On GD 45, 55 and 65, pregnant animals were euthanized 2h after the last daily dose. Maternal and fetal body weights and fetal hippocampal brain weight were determined. Maternal and fetal samples were collected for the determination of liver CYP2E1 enzymatic activity and plasma free cortisol and ACTH concentrations. RESULTS: CEE, with maternal blood ethanol concentration of 108-124 mg/dl at 2h after the last dose, decreased fetal hippocampal weight only at GD 65 and had no effect on fetal body weight compared with control. CYP2E1 activity increased with gestational age in the fetal liver microsomal and mitochondrial fractions. CEE increased CYP2E1 activity in the microsomal and mitochondrial fractions of maternal liver at the three gestational ages and in both hepatic subcellular fractions of the GD 65 fetus compared with control. There was a gestational-age-dependent increase in maternal and fetal plasma free cortisol concentrations, but no effect of CEE compared with control. Maternal and fetal plasma ACTH concentrations were unaffected by CEE compared with control, and were virtually unchanged during the third-trimester-equivalent that was studied. CONCLUSION: These data demonstrate that, in the pregnant guinea pig, this CEE regimen increases liver CYP2E1 activity, without affecting HPA axis function, in the maternal-fetal unit during near-term gestation. The CEE-induced increase in liver CYP2E1 activity and potential oxidative stress in the maternal-fetal unit may play a role in the pathogenesis of ethanol teratogenicity.

Chronic prenatal ethanol exposure increases disinhibition and perseverative responding in the adult guinea pig.

Cognitive and behavioural deficits, including increased impulsivity and perseveration, are associated with chronic prenatal ethanol exposure (CPEE) in humans. We tested whether these same deficits occur in the guinea pig after CPEE treatment. Pregnant guinea pigs received oral administration of ethanol (4 g/kg maternal body weight/day), or isocaloric-sucrose/pair-feeding throughout gestation. Young adult offspring were trained in lever-pressing paradigms to work for a sucrose-pellet food reward. CPEE increased No-Go, but not Go, responses in the Go/No-Go paradigm, indicative of a disinhibition deficit in these animals. Perseverative responses in the Cued Alternation task were also increased in CPEE offspring. These data show that CPEE induces behavioural deficits in the guinea pig that are remarkably similar to the executive function deficits that follow prenatal ethanol exposure in humans.

Repeated ethanol exposure during late gestation decreases nephron endowment in fetal sheep.

Maternal alcohol consumption during pregnancy can affect fetal development, but little is known about the effects on the developing kidney. Our objectives were to determine the effects of repeated ethanol exposure during the latter half of gestation on glomerular (nephron) number and expression of key genes involved in renal development or function in the ovine fetal kidney. Pregnant ewes received daily intravenous infusion of ethanol (0.75 g/kg, n=5) or saline (control, n=5) over 1 h from 95 to 133 days of gestational age (DGA; term is approximately 147 DGA). Maternal and fetal arterial blood samples were taken before and after the start of the daily ethanol infusions for determination of blood ethanol concentration (BEC). Necropsy was performed at 134 DGA, and fetal kidneys were collected for determination of total glomerular number using the physical disector/fractionator technique; at this gestational age nephrogenesis is completed in sheep. Maximal maternal and fetal BECs of 0.12+/-0.01 g/dl (mean+/-SE) and 0.11+/-0.01 g/dl, respectively, were reached 1 h after starting maternal ethanol infusions. Ethanol exposure had no effect on fetal body weight, kidney weight, or the gene expression of members of the renin-angiotensin system, insulin-like growth factors, and sodium channels. However, fetal glomerular number was lower after ethanol exposure (377,585+/-8,325) than in controls (423,177+/-17,178, P<0.001). The data demonstrate that our regimen of fetal ethanol exposure during the latter half of gestation results in an 11% reduction in nephron endowment without affecting the overall growth of the kidney or fetus or the expression of key genes involved in renal development or function. A reduced nephron endowment of this magnitude could have important implications for the cardiovascular health of offspring during postnatal life.

Altered water-maze search behavior in adult guinea pigs following chronic prenatal ethanol exposure: lack of mitigation by postnatal fluoxetine treatment.

Ingestion of ethanol during pregnancy can result in teratogenic effects in humans, including significant and long-lasting neurobehavioral deficits. Similar results are seen in guinea pigs with chronic prenatal ethanol exposure (CPEE) via maternal ethanol administration, which produces deficits in Morris water-maze performance and impaired hippocampal functioning (e.g., decreased long-term potentiation, LTP). In this study, we tested whether postnatal treatment with fluoxetine, a selective serotonin reuptake inhibitor, decreases some of the neurobehavioral impairments produced by CPEE. Timed, pregnant guinea pigs received oral administration of ethanol (4g/kg maternal body weight) or isocaloric sucrose pair feeding (control) for 5 days/week throughout gestation. Offspring of the CPEE and control groups were randomly assigned to receive either fluoxetine (10mg/kg body weight/day) or saline intraperitoneally from postnatal day 10 to 48. Subsequent behavioral tests in the Morris water-maze revealed a significant increase in thigmotaxic swimming in CPEE offspring without apparent signs of impairment in spatial mapping of the hidden escape platform. Measures of hippocampal short- and long-term plasticity (paired-pulse facilitation, frequency facilitation, and LTP) were unaffected by CPEE, consistent with the behavioral data indicating normal hippocampal functioning. Postnatal fluoxetine administration resulted in a significant loss of body weight, but did not affect the increased thigmotaxic swimming following CPEE. These results indicate that changes in search strategies in the water-maze might be a highly sensitive index of CPEE-induced neurobehavioral toxicity that can occur in the absence of significant hippocampal dysfunction. Further, these data demonstrate that fluoxetine, at the selected treatment regime, does not mitigate the thigmotaxic swimming response to CPEE in the guinea pig.