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B M Cooke

Publications and source records attributed to B M Cooke.

At least 19 recordsLinked to original sources
PubMed2005

Steroid-dependent plasticity in the medial amygdala.

Behavioral sex differences have traditionally been thought to arise from gonadal steroids during a neonatal sensitive period. However, it is possible to sex-reverse certain behaviors by reversing the levels of circulating androgen in adult males and females. These results suggest that the sexually dimorphic substrates of sex behavior are subject to a high degree of plasticity, even in adulthood. I have found that circulating androgen exerts a trophic effect on the Nissl-stained morphology of an important nucleus in the control of sex behavior, namely, the posterodorsal subnucleus of the medial amygdala. First, sex-reversing the level of circulating androgen reversed the sex difference in soma size and regional volume of the posterodorsal subnucleus of the medial amygdala in adult rats. Interestingly, activation of both androgen and estrogen receptors was necessary for the post-castration maintenance of a masculine phenotype in terms of posterodorsal subnucleus of the medial amygdala cell size, whereas only estrogen receptor activity was necessary to maintain a masculine posterodorsal subnucleus of the medial amygdala volume. Then, we showed that seasonal variation in androgen was correlated with morphologic plasticity in the posterodorsal subnucleus of the medial amygdala of the Siberian hamster. However, if the experimental males were housed with females, their posterodorsal subnucleus of the medial amygdalas failed to regress in response to winter-like short daylengths. Furthermore, when male hamsters were castrated and treated with testosterone, the posterodorsal subnucleus of the medial amygdala responded to the hormone only if the animals were in summer-like photoperiods. Overall, these findings indicate that circulating androgens are critical for the maintenance of greater posterodorsal subnucleus of the medial amygdala regional volumes and soma sizes, and that environmental variables can regulate testosterone secretion and responsiveness.

Amygdala↗
PubMed2001

Photoperiod and social cues influence the medial amygdala but not the bed nucleus of the stria terminalis in the Siberian hamster.

We investigated whether the posterodorsal nucleus of the medial amygdala (MePD) and the posteromedial nucleus of the bed nucleus of the stria terminalis (BSTpm) undergo structural changes in response to photoperiod or social environment in the Siberian hamster, a seasonally breeding rodent. Adult male hamsters were either kept in long days (LD; 15:9 h light:dark) from birth or were transferred at 12-16 weeks of age to short days (SD; 8:16) and housed with a male conspecific for 11 weeks. Other males were transferred to SD but were housed with an unrelated female conspecific from LD. Males transferred to SD without a female cagemate displayed testicular regression, but males transferred to SD with a female cagemate did not. The regional volume and average soma size of the BSTpm and the MePD were estimated using Nissl-stained brain sections. Neither photoperiod nor social condition modified either of the BSTpm measures. Among males housed in same-sex groups, the average soma size in the MePD was significantly smaller in SD males than in LD males. Cohabitation with a female resulted in MePD volumes indistinguishable from LD males. These results indicate that the MePD, a nucleus implicated in socio-sexual behavior, can respond to photoperiodic as well as to social cues.

Amygdala↗
PubMed2001

Babesia bovis: culture of laboratory-adapted parasite lines and clinical isolates in a chemically defined medium.

Babesiosis caused by Babesia spp. is a disease of both veterinary and human importance. Here, we describe a method to continuously culture laboratory lines and field isolates of Babesia bovis in vitro in a chemically defined medium using (ALBU)MAX II as an alternative to bovine serum. Further, we have successfully cultured parasite isolates directly from cattle that failed to grow in traditional serum-containing medium. Variation of atmospheric gas composition and culture volumes to determine optimal growth conditions revealed that a 600-microl culture in an atmosphere comprising 5% O(2), 5% CO(2), and 90% N(2) achieved a significantly higher percentage of parasitized red blood cells than any other combination tested. The process could be scaled up to reliably produce large volumes of parasites. Supplementation of the culture medium with hypoxanthine further improved parasite growth. B. bovis cultured in this way could be the basis of an alternative, safer vaccine and a reliable source of parasites and exoantigens for parasitological research.

Animals↗
PubMed2001

The malaria-infected red blood cell: structural and functional changes.

The asexual stage of malaria parasites of the genus Plasmodium invade red blood cells of various species including humans. After parasite invasion, red blood cells progressively acquire a new set of properties and are converted into more typical, although still simpler, eukaryotic cells by the appearance of new structures in the red blood cell cytoplasm, and new proteins at the red blood cell membrane skeleton. The red blood cell undergoes striking morphological alterations and its rheological properties are considerably altered, manifesting as red blood cells with increased membrane rigidity, reduced deformability and increased adhesiveness for a number of other cells including the vascular endothelium. Elucidation of the structural changes in the red blood cell induced by parasite invasion and maturation and an understanding of the accompanying functional alterations have the ability to considerably extend our knowledge of structure-function relationships in the normal red blood cell. Furthermore, interference with these interactions may lead to previously unsuspected means of reducing parasite virulence and may lead to the development of novel antimalarial therapeutics.

Animals↗
PubMed2000

Post-weaning social isolation of male rats reduces the volume of the medial amygdala and leads to deficits in adult sexual behavior.

At 21 days of age, gonadally intact male Long Evans rats were weaned and placed into standard laboratory conditions (three per cage) or housed singly. They were tested for noncontact erections and sexual performance at 90 and 220 days of age. Rats raised in isolation displayed significantly fewer noncontact erections in response to sensory cues from an estrous female and fewer intromissions when allowed to mate with a female than did males raised in groups. The volume of the posterodorsal component of the medial amygdala (MePD) and the size of neurons within the MePD were significantly smaller in the isolated males than in socially housed males. Similarly, neurons in the sexually dimorphic nucleus of the preoptic area (SDN-POA) were smaller in isolate animals than in controls. As both MePD volume and SDN-POA soma size are responsive to sex steroids, these differences could result if the isolates experienced lower testosterone levels. Finally, the volume of the overall medial amygdala (MeA) correlated significantly with the number of noncontact erections, a relationship that was not explained by housing condition. These findings highlight the role of social experience as a factor in the sexual differentiation of the brain and suggest a positive relationship between the volume of a brain structure and the display of sexual behaviors.

Age Factors↗
PubMed2000

Targeted mutagenesis of Plasmodium falciparum erythrocyte membrane protein 3 (PfEMP3) disrupts cytoadherence of malaria-infected red blood cells.

Adhesion of parasite-infected red blood cells to the vascular endothelium is a critical event in the pathogenesis of malaria caused by Plasmodium falciparum. Adherence is mediated by the variant erythrocyte membrane protein 1 (PfEMP1). Another protein, erythrocyte membrane protein-3 (PfEMP3), is deposited under the membrane of the parasite-infected erythrocyte but its function is unknown. Here we show that mutation of PfEMP3 disrupts transfer of PfEMP1 to the outside of the P.FALCIPARUM:-infected cell. Truncation of the C-terminal end of PfEMP3 by transfection prevents distribution of this large (>300 kDa) protein around the membrane but does not disrupt trafficking of the protein from the parasite to the cytoplasmic face of the erythrocyte membrane. The truncated PfEMP3 accumulates in structures that appear to be associated with the erythrocyte membrane. We show that accumulation of mutated PfEMP3 blocks the transfer of PfEMP1 onto the outside of the parasitized cell surface and suggest that these proteins traffic through an erythrocyte membrane-associated compartment that is involved in the transfer of PfEMP1 to the surface of the parasite-infected red blood cell.

Animals↗
PubMed2000

Molecular approaches to malaria: seeking the whole picture.

This year, Australia hosted its first major international conference on malaria - Molecular Approaches to Malaria in Lorne, Victoria, 2-5 February 2000 (MAM2000). The worldwide research effort toward a better understanding of the pathogenesis and control of malaria in the post-genomic era was discussed and debated by over 250 researchers from 18 countries during four days packed with molecular biology, cell biology, genomics, vaccines and pathogenic mechanisms. This special malaria edition of Parasitology Today is an attempt to capture and summarize the quality and breadth of work presented at the conference and place this in the context of the current global malaria research effort; eight of the nine Reviews in this issue have been written by session chairs or presenters at MAM2000.

Animals↗
PubMed2000

Adhesion of Plasmodium falciparum-infected erythrocytes to hyaluronic acid in placental malaria.

Infection with Plasmodium falciparum during pregnancy leads to the accumulation of parasite-infected erythrocytes in the placenta, and is associated with excess perinatal mortality, premature delivery and intrauterine growth retardation in the infant, as well as increased maternal mortality and morbidity. P. falciparum can adhere to specific receptors on host cells, an important virulence factor enabling parasites to accumulate in various organs. We report here that most P. falciparum isolates from infected placentae can bind to hyaluronic acid, a newly discovered receptor for parasite adhesion that is present on the placental lining. In laboratory isolates selected for specific high-level adhesion, binding to hyaluronic acid could be inhibited by dodecamer or larger oligosaccharide fragments or polysaccharides, treatment of immobilized receptor with hyaluronidase, or treatment of infected erythrocytes with trypsin. In vitro flow-based assays demonstrated that high levels of adhesion occurred at low wall shear stress, conditions thought to prevail in the placenta. Our findings indicate that adhesion to hyaluronic acid is involved in mediating placental parasite accumulation, thus changing the present understanding of the mechanisms of placental infection, with implications for the development of therapeutic and preventative interventions.

Animals↗
PubMed1999

Mapping the binding domains involved in the interaction between the Plasmodium falciparum knob-associated histidine-rich protein (KAHRP) and the cytoadherence ligand P. falciparum erythrocyte membrane protein 1 (PfEMP1).

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) clusters at electron-dense knob-like structures on the surface of malaria-infected red blood cells and mediates their adhesion to the vascular endothelium. In parasites lacking knobs, vascular adhesion is less efficient, and infected red cells are not able to immobilize successfully under hemodynamic flow conditions even though PfEMP1 is still present on the exterior of the infected red cell. We examined the interaction between the knob-associated histidine-rich protein (KAHRP), the parasite protein upon which knob formation is dependent, and PfEMP1, and we show evidence of a direct interaction between KAHRP and the cytoplasmic region of PfEMP1 (VARC). We have identified three fragments of KAHRP which bind VARC. Two of these KAHRP fragments (K1A and K2A) interact with VARC with binding affinities (K(D(kin))) of 1 x 10(-7) M and 3.3 x 10(-6) M respectively, values comparable to those reported previously for protein-protein interactions in normal and infected red cells. Further experiments localized the high affinity binding regions of KAHRP to the 63-residue histidine-rich and 70-residue 5' repeats. Deletion of these two regions from the KAHRP fragments abolished their ability to bind to VARC. Identification of the critical domains involved in interaction between KAHRP and PfEMP1 may aid development of new therapies to prevent serious complications of P. falciparum malaria.

Animals↗
PubMed1999

A brain sexual dimorphism controlled by adult circulating androgens.

Reports of structural differences between the brains of men and women, heterosexual and homosexual men, and male-to-female transsexuals and other men have been offered as evidence that the behavioral differences between these groups are likely caused by differences in the early development of the brain. However, a possible confounding variable is the concentration of circulating hormones seen in these groups in adulthood. Evaluation of this possibility hinges on the extent to which circulating hormones can alter the size of mammalian brain regions as revealed by Nissl stains. We now report a sexual dimorphism in the volume of a brain nucleus in rats that can be completely accounted for by adult sex differences in circulating androgen. The posterodorsal nucleus of the medial amygdala (MePD) has a greater volume in male rats than in females, but adult castration of males causes the volume to shrink to female values within four weeks, whereas androgen treatment of adult females for that period enlarges the MePD to levels equivalent to normal males. This report demonstrates that adult hormone manipulations can completely reverse a sexual dimorphism in brain regional volume in a mammalian species. The sex difference and androgen responsiveness of MePD volume is reflected in the soma size of neurons there.

Amygdala↗
PubMed1999

Sex difference and laterality in the volume of mouse dentate gyrus granule cell layer.

Sex differences in spatial learning have been reported in both humans and rodents. Correspondingly, there have been reports of sexual dimorphism in the morphology of the hippocampal formation (HF), a brain structure implicated in spatial cognition. In Experiment 1, we confirmed earlier reports that the overall volume of the granule cell layer (GCL) of the dentate gyrus (DG) of A/J mice is larger in males than in females. We also found that male A/J mice have a larger GCL volume in the right hemisphere than the left. Female A/J mice displayed no such laterality. A similar pattern of laterality, favoring the right HF, had been reported previously in male, but not female, rats. In Experiment 2, we examined mice with a defective structural gene for androgen receptors (testicular feminization mutant, or tfm mice) on a C57/BL6J background. The C57/J strain had not previously been examined for hippocampal sexual dimorphism. We found no sexual dimorphism in the left, right, or total volume of the GCL in C57/BL6J mice whether they were wildtype or tfm. However, the right GCL volume was greater than the left in wildtype C57/BL6J mice of either sex. No lateralization of GCL volume was found in the androgen-insensitive tfm-affected males or the partially androgen-insensitive tfm-carrier females. These findings confirm earlier reports that sexual dimorphism in mouse HF is found in some inbred strains but not others, and indicate for the first time that mouse HF structures are lateralized. The absence of lateralization in partially or wholly androgen-insensitive mice suggests that androgen receptors may play a role in development of laterality in the GCL independently of any sexual dimorphism in this structure.

Androgen-Insensitivity Syndrome↗
PubMed1999

Glycoprotein (GP) Ib-IX-transfected cells roll on a von Willebrand factor matrix under flow. Importance of the GPib/actin-binding protein (ABP-280) interaction in maintaining adhesion under high shear.

Adhesion of platelets to sites of vascular injury is critical for hemostasis and thrombosis and is dependent on the binding of the vascular adhesive protein von Willebrand factor (vWf) to the glycoprotein (GP) Ib-V-IX complex on the platelet surface. A unique but poorly defined characteristic of this receptor/ligand interaction is its ability to support platelet adhesion under conditions of high shear stress. To examine the structural domains of the GPIb-V-IX complex involved in mediating cell adhesion under flow, we have expressed partial (GPIb-IX), complete (GPIb-V-IX), and mutant (GPIbalpha cytoplasmic tail mutants) receptor complexes on the surface of Chinese hamster ovary (CHO) cells and examined their ability to adhere to a vWf matrix in flow-based adhesion assays. Our studies demonstrate that the partial receptor complex (GPIb-IX) supports CHO cell tethering and rolling on a bovine or human vWf matrix under flow. The adhesion was specifically inhibited by an anti-GPIbalpha blocking antibody (AK2) and was not observed with CHO cells expressing GPIbbeta and GPIX alone. The velocity of rolling was dependent on the level of shear stress, receptor density, and matrix concentration and was not altered by the presence of GPV. In contrast to selectins, which mediate cell rolling under conditions of low shear (20-200 s-1), GPIb-IX was able to support cell rolling at both venous (150 s-1) and arterial (1500-10,500 s-1) shear rates. Studies with a mutant GPIbalpha receptor subunit lacking the binding domain for actin-binding protein demonstrated that the association of the receptor complex with the membrane skeleton is not essential for cell tethering or rolling under low shear conditions, but is critical for maintaining adhesion at high shear rates (3000-6000 s-1). These studies demonstrate that the GPIb-IX complex is sufficient to mediate cell rolling on a vWf matrix at both venous and arterial levels of shear independent of other platelet adhesion receptors. Furthermore, our results suggest that the association between GPIbalpha and actin-binding protein plays an important role in enabling cells to remain tethered to a vWf matrix under conditions of high shear stress.

Animals↗
PubMed1999

The orthodox view of brain sexual differentiation.

The standard view of sexual differentiation of the brain, derived primarily from work with mammals, is that the same steroidal signal which permanently masculinizes the body early in life, androgen, also permanently masculinizes the nervous system. This oversimplified view overlooks the rich diversity of mechanisms produced by natural selection. We review the mechanisms underlying sexual differentiation of what may be the simplest mammalian model, the spinal nucleus of the bulbocavernosus (SNB), a system that is intimately associated with sexual differentiation of the periphery. Indeed, in many instances, early androgen can permanently masculinize the SNB system but, surprisingly, these early influences may depend to some extent on social mediating factors. Furthermore, in adulthood, androgen continues to affect the SNB system in diverse ways, acting on several different loci, indicating a life-long plasticity in even this simple system. Finally, there is evidence that adult androgens interact with social experience in order to affect the SNB system. Thus the SNB system displays a far richer array of interactions than the standard view of sexual differentiation would predict. Examination of other systems and other species, as depicted in the following reports, reveals a far more complicated, and far more interesting perspective on how the brains and behaviors of males and females diverge.

Amygdala↗