Cardiac and splenic levels of norepinephrine and dopamine in copper deficient pigs and rats

1. Copper deficiency decreased the concentration and content of norepinephrine in the hearts of pigs and rats. 2. Concentration, but not content, of norepinephrine was decreased in spleen of copper-deficient pigs, while splenic norepinephrine levels in rats were not altered by copper deficiency. 3. Cardiac and splenic concentrations and contents of dopamine were elevated in copper-deficient pigs and rats. 4. Tissue concentrations of catecholamines and the magnitude of change due to copper deficiency were greater in pigs than rats.     

Telltale eyes: the lateral visual systems of Rhenish Lower Devonian eurypterids (Arthropoda,Chelicerata) and their palaeobiological implications

The compound eyes of three taxa of Rhenish Lower Devonian eurypterids are examined and compared with those known from other eurypterids and the extant horseshoe crab Limulus polyphemus. The lateral eyes of the small species Rhenopterus diensti, a phylogenetically basal representative of the stylonurine clade, are characterized by a comparatively low number of lenses and high interommatidial angle Δφ (2.8°). The comparatively limited visual capacities of R. diensti are more similar to L. polyphemus than to its closer relatives of the eurypterine clade and perhaps this reflects a progression of lateral eye structure in the evolution of eurypterids as a whole. The number of eye facets in Adelophthalmus sievertsi is higher than that in the supposed ambush predator Acutiramus cummingsi, but lower than that in other ‘swimming’ eurypterids (Eurypterina). Due to poor preservation, no other eye parameters could be analysed in this species, but further morphological attributes and geographical distribution designate the mid‐sized A. sievertsi as an able swimmer. A low interommatidial angle Δφ of less than 1° confirms that the visual capacities of Jaekelopterus rhenaniae are in line with an interpretation of this giant species as an active high‐level predator. The inferred lifestyles of adult individuals of these three, co‐occurring Rhenish eurypterids indicate niche differentiation avoiding to some degree the competition for food in their marginal marine to delta plain transitional habitats.     

Short-term pituitary-testicular responses of prepubertal ram lambs to hemicastration

To examine the short-term effects of hemicastration on pituitary-gonadal responses, 12 ram lambs were anesthetized and hemicastrated at 4 mo of age and killed (n = 4) at 2 (HC2), 7 (HC7), or 14 (HC14) days following surgery. Four intact (INT) rams were killed 14 days following anesthesia. Testis and pituitary weights were similar between HC and INT rams. Serum follicle-stimulating hormone (FSH) in HC rams increased within 6 h, peaked at 12 h, and remained elevated above INT levels throughout the study. Overall mean serum testosterone levels in HC rams were lower than in INT rams for the first 48 h, but were similar by 3 days post-surgery. Pulsatile luteinizing hormone (LH) and testosterone secretion was suppressed for the first 9.5 h following anesthesia and/or surgery in both HC and INT animals. A single LH pulse and succeeding testosterone pulse occurred in 10/12 HC and 4/4 INT rams between 10 and 14 h post-surgery, both of which were lower in amplitude in HC than INT animals. However, on Day 7, pulsatile secretory patterns of LH and testosterone were similar, suggesting compensatory androgen secretion had occurred in HC rams. Pituitary LH content was unaffected by hemicastration. In contrast, pituitary FSH content was greater in HC7 and HC14 compared to HC2 and INT animals. Pituitary gonadotropin hormone-releasing hormone (GnRH) receptor concentrations were similar in INT, HC7, and HC14 rams, but were slightly reduced in HC2 rams. Neither testicular LH nor FSH receptor concentrations were altered by hemicastration at any time.(ABSTRACT TRUNCATED AT 250 WORDS)     

Consequences of copper deficiency are not differentially influenced by carbohydrate source in young pigs fed a dired skim milk-based diet

Carbohydrates (CHO) such as fructose (FR) or sucrose, but not starch (ST), aggravate the consequences of dietary copper (Cu) deficiency in rats. To evaluate whether this Cu X CHO interaction is pertinent to human health, the pig was used as an animal model. In two studies, 66 weanling pigs were fed dried skim milk (DSM)-based diets for 10 wk with 20% of the total calories provided as either FR, glucose, or ST and containing either deficient (1.0-1.3 micrograms/g diet) or adequate (7.1 micrograms/g) levels of Cu. Plasma and tissue levels of Cu, the activities of plasma ceruloplasmin ferroxidase and erythrocyte Cu, Zn-superoxide dismutase, and hematocrits were lower (p less than 0.05) in animals fed Cu-deficient diets. The relative cardiac mass of all Cu-deficient groups was greater (p less than 0.05) than that of animals fed Cu-adequate diets. These effects were in general unaffected by type of CHO. For comparison, weaned male rats were also fed DSM-based containing diets ST or FR with adequate or deficient Cu for as long as 10 wk. Rats consuming the Cu-deficient diets were characterized by significantly lower hematocrits, decreased tissue Cu levels, and enlarged hearts, regardless of the CHO source. Together, these data demonstrate that DSM-based diets are not suitable for delineation of potential Cu X CHO interactions, and one or more components of DSM may exacerbate the consequences of dietary Cu deficiency.     

Pituitary luteinizing hormone-releasing hormone receptors in ovariectomized cows after challenge with ovarian steroids

Acute changes of bovine pituitary luteinizing hormone-releasing hormone (LHRH) receptors in response to steroid challenges have not been documented. To investigate these changes 96 ovariectomized (OVX) cows were randomly allotted to one of the following treatments: 1) 1 mg estriol (E3); 2) 1 mg 17 beta-estradiol (E2); or 3) 25 mg progesterone (P) twice daily for 7 days before 1 mg E2 and continuing to the end of the experiment. Serum was collected at hourly intervals from 4 animals in each group for 28 h following estrogen treatment. Four animals from each treatment were killed at 4-h intervals from 0 to 28 h after estrogen injection to recover pituitaries and hypothalami. Treatment with E3 or E2 decreased serum luteinizing hormone (LH) within 3 h and was followed by surges of LH that were temporally and quantitatively similar (P greater than 0.05). Progesterone did not block the decline in serum LH, but did prevent (P less than 0.05) the E2-induced surge of LH. Serum follicle-stimulating hormone (FSH) was unaffected (P less than 0.05) by treatment. Pituitary concentrations of LH and FSH were maximal (P less than 0.001) at 16 h for E3 and 20 h for E2, whereas P prevented (P greater than 0.05) the pituitary gonadotropin increase. Concentrations of LHRH in the hypothalamus were similar (P greater than 0.05) among treatments. Pituitary concentrations of receptors for LHRH were maximal (P less than 0.005) 12 h after estrogen injection (approximately 8 h before the LH surge), even in the presence of P. This study demonstrated that in the OVX cow: 1) E2 and E3 increased the concentration of receptors for LHRH and this increase occurred before the surge of LH; and 2) P did not block the E2-induced increase in pituitary receptors for LHRH but did prevent the surge of LH.     

The coevolution of play and the cortico-cerebellar system in primates

Primates are some of the most playful animals in the natural world, yet the reason for this remains unclear. One hypothesis posits that primates are so playful because playful activity functions to help develop the sophisticated cognitive and behavioural abilities that they are also renowned for. If this hypothesis were true, then play might be expected to have coevolved with the neural substrates underlying these abilities in primates. Here, we tested this prediction by conducting phylogenetic comparative analyses to determine whether play has coevolved with the cortico-cerebellar system, a neural system known to be involved in complex cognition and the production of complex behaviour. We used phylogenetic generalised least squares analyses to compare the relative volume of the largest constituent parts of the primate cortico-cerebellar system (prefrontal cortex, non-prefrontal heteromodal cortical association areas, and posterior cerebellar hemispheres) to the mean percentage of time budget spent in play by a sample of primate species. Using a second categorical data set on play, we also used phylogenetic analysis of covariance to test for significant differences in the volume of the components of the cortico-cerebellar system among primate species exhibiting one of three different levels of adult-adult social play. Our results suggest that, in general, a positive association exists between the amount of play exhibited and the relative size of the main components of the cortico-cerebellar system in our sample of primate species. Although the explanatory power of this study is limited by the correlational nature of its analyses and by the quantity and quality of the data currently available, this finding nevertheless lends support to the hypothesis that play functions to aid the development of cognitive and behavioural abilities in primates.     

Random screening of proteins for HLA-A*0201-binding nine-amino acid peptides is not sufficient for identifying CD8 T cell epitopes recognized in the context of HLA-A*0201

HLA-A2 is the most frequent HLA molecule in Caucasians with HLA-A*0201 representing the most frequent allele; it was also the first human HLA allele for which peptide binding prediction was developed. The Bioinformatics and Molecular Analysis Section of the National Institutes of Health (BIMAS) and the University of Tübingen (Syfpeithi) provide the most popular prediction algorithms of peptide/MHC interaction on the World Wide Web. To test these predictions, HLA-A*0201-binding nine-amino acid peptides were searched by both algorithms in 19 structural CMV proteins. According to Syfpeithi, the top 2% of predicted peptides should contain the naturally presented epitopes in 80% of predictions (www.syfpeithi.de). Because of the high number of predicted peptides, the analysis was limited to 10 randomly chosen proteins. The top 2% of peptides predicted by both algorithms were synthesized corresponding to 261 peptides in total. PBMC from 10 HLA-A*0201-positive and CMV-seropositive healthy blood donors were tested by ex vivo stimulation with all 261 peptides using crossover peptide pools. IFN-gamma production in T cells measured by CFC was used as readout. However, only one peptide was found to be stimulating in one single donor. As a result of this work, we report a potential new T cell target protein, one previously unknown CD8-T cell-stimulating peptide, and an extensive list of CMV-derived potentially strong HLA-A*0201-binding peptides that are not recognized by T cells of HLA-A*0201-positive CMV-seropositive donors. We conclude that MHC/peptide binding predictions are helpful for locating epitopes in known target proteins but not necessarily for screening epitopes in proteins not known to be T cell targets.     

Aberrant expression of HLA-B*3565Q is associated with a disrupted disulfide bond

The identification of expression variants is a challenge in HLA diagnostics. We here describe the identification of the novel allele HLA-B*3565Q. The serological HLA class I type, as determined by a lymphocytotoxicity test, was A11,24; B38; Bw4; Cw−; whereas PCR-sequence-specific primers resulted in A*11,*24, B*35,*38; Cw*12, thus suggesting the presence of a nonexpressed B*35 allele. To clarify the lack of serological HLA-B35 reactivity, exons 2 and 3 were sequenced following haplotype-specific amplification. At position 564 from the beginning of the coding region (exon 3), a transversion (C→G) was observed, which, at the amino acid level, results in a substitution from cysteine to tryptophane at position 164 of the mature polypeptide. Because this position is essential for the formation of a disulfide bond linking the cysteine residues at positions 101 and 164, which is strongly conserved in functional class I molecules of vertebrates, the disruption of this bond is very likely to be the reason for the lack of serological detectability. We later found the same novel allele in a second unrelated individual, of whom we were able to establish a lymphoblastoid cell line (B-LCL). Serological testing of this B-LCL indicated a very low aberrant expression of HLA-B*3565Q, which cannot be expected to be detected by standard serology techniques. Holger-Andreas Elsner and Peter A. Horn contributed equally to this work. The nucleotide sequence data reported in this paper have been published in the European Molecular Biology Laboratory, GenBank, and DNA Data Bank of Japan Nucleotide Sequence Database under the accession numbers AJ278746, AJ278747, and AJ879892. The name B*3565Q was officially assigned by the WHO Nomenclature Committee in December 2005. This follows the agreed policy that, subject to the conditions stated in the most recent Nomenclature Report (Marsh et al. 2005), names will be assigned to new sequences as they are identified. Lists of such new names will be published in the following WHO Nomenclature Report.     

Increased bioactivity of serum follicle-stimulating hormone, but not luteinizing hormone, following hemicastration in ram lambs

This study evaluated the short-term effects of hemicastration on levels of bioactive (bio-) and immunoactive (immuno-) FSH and LH in 3.5-mo-old ram lambs. Biological activities of FSH and LH were determined using in vitro rat granulosa cell aromatase and mouse Leydig cell testosterone assays, respectively. Four rams each were either hemicastrated (HC) or left intact (INT) and blood samples were collected over a 2-wk period. In HC rams, serum bio- and immuno-FSH concentrations increased several fold within 5-8 h after surgery and remained elevated over INT controls for 7 and 14 days, respectively. The increase in bio-FSH was greater than that for immuno-FSH, resulting in an increase in the ratio of biological to immunological activity (B/I ratio) through Day 7. Neither immuno-FSH, bio-FSH, nor the B/I ratios varied throughout the 2-wk study in INT rams. In contrast to FSH, serum concentrations of immuno- and bio-LH and the B/I ratios were similar between HC and INT rams. For both gonadotropins, biological activity was positively correlated to immunological activity. These results demonstrate that (1) immuno- and bio-FSH concentrations are elevated after hemicastration; (2) the FSH biopotency (B/I ratio) also is increased, at least temporarily; and (3), despite these changes in FSH production, neither immuno- nor bio-LH secretion is altered by hemicastration.     

The sophisticated visual system of a tiny Cambrian crustacean: analysis of a stalked fossil compound eye

Fossilized compound eyes from the Cambrian, isolated and three-dimensionally preserved, provide remarkable insights into the lifestyle and habitat of their owners. The tiny stalked compound eyes described here probably possessed too few facets to form a proper image, but they represent a sophisticated system for detecting moving objects. The eyes are preserved as almost solid, mace-shaped blocks of phosphate, in which the original positions of the rhabdoms in one specimen are retained as deep cavities. Analysis of the optical axes reveals four visual areas, each with different properties in acuity of vision. They are surveyed by lenses directed forwards, laterally, backwards and inwards, respectively. The most intriguing of these is the putatively inwardly orientated zone, where the optical axes, like those orientated to the front, interfere with axes of the other eye of the contralateral side. The result is a three-dimensional visual net that covers not only the front, but extends also far laterally to either side. Thus, a moving object could be perceived by a two-dimensional coordinate (which is formed by two axes of those facets, one of the left and one of the right eye, which are orientated towards the moving object) in a wide three-dimensional space. This compound eye system enables small arthropods equipped with an eye of low acuity to estimate velocity, size or distance of possible food items efficiently. The eyes are interpreted as having been derived from individuals of the early crustacean Henningsmoenicaris scutula pointing to the existence of highly efficiently developed eyes in the early evolutionary lineage leading towards the modern Crustacea.