Severe psychiatric disorders such as schizophrenia, bipolar disorder and major depressive disorder are brain diseases of unknown origin. No biological marker has been documented at the pathological, cellular, or molecular level, suggesting that a number of complex but subtle changes underlie these illnesses. We have used proteomic technology to survey postmortem tissue to identify changes linked to the various diseases. Proteomics uses two-dimensional gel electrophoresis and mass spectrometric sequencing of proteins to allow the comparison of subsets of expressed proteins among a large number of samples. This form of analysis was combined with a multivariate statistical model to study changes in protein levels in 89 frontal cortices obtained postmortem from individuals with schizophrenia, bipolar disorder, major depressive disorder, and non-psychiatric controls. We identified eight protein species that display disease-specific alterations in level in the frontal cortex. Six show decreases compared with the non-psychiatric controls for one or more diseases. Four of these are forms of glial fibrillary acidic protein (GFAP), one is dihydropyrimidinase-related protein 2, and the sixth is ubiquinone cytochrome c reductase core protein 1. Two spots, carbonic anhydrase 1 and fructose biphosphate aldolase C, show increase in one or more diseases compared to controls. Proteomic analysis may identify novel pathogenic mechanisms of human neuropsychiatric diseases. Molecular Psychiatry (2000) 5, 142-149.

Two synchronization protocols were tested for lactating dairy cows and heifers. Nulliparous dairy heifers (13 to 23 mo; n = 155) and primiparous and multiparous dairy cows (60 to 289 d postpartum; n = 310) were assigned randomly to two treatments. Controls received 25 mg of PGF2 alpha and were artificially inseminated according to the a.m.-p.m. rule following detected estrus. All controls that were not detected in estrus were injected with 25 mg of PGF2 alpha at 14-d intervals until artificial insemination (AI) at a detected estrus or until timed AI at 72 to 80 h after a third sequential injection of PGF2 alpha. Treated cows and heifers received a protocol that used GnRH and PGF2 alpha to synchronize ovulation (Ovsynch). Cows and heifers that were treated with Ovsynch were injected i.m. with 100 micrograms of GnRH at a random stage of the estrous cycle. Seven days later, cows and heifers in this group received 25 mg of PGF2 alpha followed by a second injection of 100 micrograms of GnRH 30 to 36 h later. Subsequently, the treated cows and heifers received AI 16 to 20 h after the second injection of GnRH. Pregnancy rates per AI were similar (38.9% vs. 37.8%) for control cows and cows treated with the Ovsynch protocol, respectively. However, pregnancy rate per AI was greater for control heifers (74.4%) than for heifers treated with Ovsynch (35.1%). Evaluation of serum progesterone concentrations at each hormonal injection indicated that the first injection of GnRH synchronized luteal function of lactating dairy cows but not of heifers. In summary, one fixed-time AI at a synchronized ovulation provided similar pregnancy rates per AI as did AI following the a.m-p.m. rule after estrus had been induced by PGF2 alpha in lactating cows, but the fixed-time AI was not effective for heifers because of the lack of synchronization.

Atrazine is the most commonly detected pesticide contaminant of ground water, surface water, and precipitation. Atrazine is also an endocrine disruptor that, among other effects, alters male reproductive tissues when animals are exposed during development. Here, we apply the nine so-called “Hill criteria” (Strength, Consistency, Specificity, Temporality, Biological Gradient, Plausibility, Coherence, Experiment, and Analogy) for establishing cause–effect relationships to examine the evidence for atrazine as an endocrine disruptor that demasculinizes and feminizes the gonads of male vertebrates. We present experimental evidence that the effects of atrazine on male development are consistent across all vertebrate classes examined and we present a state of the art summary of the mechanisms by which atrazine acts as an endocrine disruptor to produce these effects. Atrazine demasculinizes male gonads producing testicular lesions associated with reduced germ cell numbers in teleost fish, amphibians, reptiles, and mammals, and induces partial and/or complete feminization in fish, amphibians, and reptiles. These effects are strong (statistically significant), consistent across vertebrate classes, and specific. Reductions in androgen levels and the induction of estrogen synthesis – demonstrated in fish, amphibians, reptiles, and mammals – represent plausible and coherent mechanisms that explain these effects. Biological gradients are observed in several of the cited studies, although threshold doses and patterns vary among species. Given that the effects on the male gonads described in all of these experimental studies occurred only after atrazine exposure, temporality is also met here. Thus the case for atrazine as an endocrine disruptor that demasculinizes and feminizes male vertebrates meets all nine of the “Hill criteria”.

Development of porcine conceptuses included transitions of five stages: blastocysts of spherical, ovoid, and tubular forms containing an embryonic disc and trophoblast, extremely elongated filamentous blastocysts, and stages of embryogenesis between days 9 and 18 after mating. Embryonic survival was reduced by 17% during this period. In this litter-bearing species, intense alteration in distribution patterns occurred at days 11 and 12, when blastocysts rapidly elongated to filamentous forms. Increased embryo mortality did not result from rapid changes in distribution patterns of conceptuses within the same uterine horn at this time. Filamentous blastocysts quickly reached lengths often exceeding 60 cm, and these conceptuses became regularly spaced with no overlap of tubular membranes from other embryos in that horn. The number of conceptuses within a uterine horn ranged from 1 to 13. Protein in individual conceptuses was used as an indicator of growth and denoted exponential increase, but at a lower rate for blastocysts of spherical, ovoid, and tubular forms as compared with that found in filamentous blastocysts and embryogenesis stage conceptuses. Growth on a conceptus, based upon its protein content, was independent of the developmental stage or potential loss of those neighbors nearest that conceptus.

Earlier studies in live pancreatic acinar cells identified new cellular structures at the cell plasma membrane called 'pits' and 'depressions', where membrane-bound secretory vesicles dock and fuse to release vesicular contents. In the current study, using atomic force microscopy we identify similar structures at the plasma membrane of GH-secreting cells of the pituitary and implicate their involvement in hormone release. Pits containing 100-200 nm in diameter depressions or fusion pores were identified in resting GH-secreting cells. Following stimulation of secretion the size of depression enlarged and gold-tagged GH antibody were found to bind to the pit structures in the stimulated GH cells. This study documents for the first time the presence of these structures and their involvement in secretions in a neuroendocrine cell.

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Background-Fructose consumption is rising and its malabsorption causes common gastrointestinal symptoms. Because its absorption capacity is poorly understood, there is no standard method of assessing fructose absorption. We performed a dose response study of fructose absorption in healthy subjects in order to develop a breath test to distinguish normal from abnormal fructose absorption capacity.

Residual feed intake (RFI) is a measure of feed efficiency, in which low RFI denotes improved feed efficiency. Caloric restriction (CR) is associated with feed efficiency in livestock species and to human health benefits, such as longevity and cancer prevention. We have developed pig lines that differ in RFI, and we are interested in identifying the genes and pathways that underlie feed efficiency. Prepubertal Yorkshire gilts with low RFI (n ϭ 10) or high RFI (n ϭ 10) were fed ad libitum or fed at restricted intake of 80% of maintenance energy requirements for 8 days. We measured serum metabolites and hormones and generated transcriptional profiles of liver and subcutaneous adipose tissue on these animals. Overall, 6,114 genes in fat and 305 genes in liver were differentially expressed (DE) in response to CR, and 311 genes in fat and 147 genes in liver were DE due to RFI differences. Pathway analyses of CR-induced DE genes indicated a dramatic switch to a conservation mode of energy usage by down-regulating lipogenesis and steroidogenesis in both liver and fat. Interestingly, CR altered expression of genes in immune and cell cycle/apoptotic pathways in fat, which may explain part of the CR-driven lifespan enhancement. In silico analysis of transcription factors revealed ESR1 as a putative regulator of the adaptive response to CR, as several targets of ESR1 in our DE fat genes were annotated as cell cycle/ apoptosis genes. The lipid metabolic pathway was overrepresented by down-regulated genes due to both CR and low RFI. We propose a common energy conservation mechanism, which may be controlled by PPARA, PPARG, and/or CREB in both CR and feed-efficient pigs. microarray; transcriptional profiling; ESR1; residual feed intake; peroxisome proliferator-activated receptor a; peroxisome proliferatoractivated receptor g; cAMP response element binding; protein GENETIC MECHANISMS THAT CONTROL feed intake (FI) and feed efficiency are not well understood. Differences in feed efficiency arise due to factors such as variations in body composition, feeding patterns, digestibility, activity, thermoregulation, and tissue metabolic rates (68). Residual feed intake (RFI) has been broadly accepted as a reliable method of measuring feed efficiency and is defined as the feed consumed above or below what is required for growth and maintenance (47, 54). Pigs with low RFI (LRFI) consume less food than the population average without a significant loss in growth parameters such as body weight and composition, and therefore, they are more feed efficient. Our group has successfully developed pig lines that differ in RFI up to 124 g/day without significant change in the body composition, with an estimated heritability for RFI of 0.33 (12). The physiology underlying RFI differences has been studied mainly in poultry and in beef cattle, in which whole-genome SNP analyses and microarray approaches have been undertaken (6, 9, 74). For example, transcriptomic analysis of liver biopsies from Angus bulls identified 163 differentially expressed genes...