Ethers of 3-hydroxyphenylacetic acid as selective gamma-hydroxybutyric acid receptor ligands

Gamma-hydroxybutyric acid (GHB) is a drug of abuse, a therapeutic, and purportedly a neurotransmitter with a complex mechanism of action in vivo due to direct actions at GABA(B) as well as GHB receptors and because of its metabolism to GABA. Herein, we describe 3-ethers of 3-hydroxyphenylacetic acid, which have relatively high affinity at GHB sites, no significant affinity at GABA receptors, and would not be expected to be rapidly metabolized to GABAergic ligands. The selectivity of these compounds (UMB108, UMB109, and UMB119) could prove to be useful for studying the biology of GHB receptors, free from GABAergic effects.     

Melatonin,immune function and aging

Aging is associated with a decline in immune function (immunosenescence), a situation known to correlate with increased incidence of cancer, infectious and degenerative diseases. Innate, cellular and humoral immunity all exhibit increased deterioration with age. A decrease in functional competence of individual natural killer (NK) cells is found with advancing age. Macrophages and granulocytes show functional decline in aging as evidenced by their diminished phagocytic activity and impairment of superoxide generation. There is also marked shift in cytokine profile as age advances, e.g., CD3+ and CD4+ cells decline in number whereas CD8+ cells increase in elderly individuals. A decline in organ specific antibodies occurs causing reduced humoral responsiveness. Circulating melatonin decreases with age and in recent years much interest has been focused on its immunomodulatory effect. Melatonin stimulates the production of progenitor cells for granulocytes-macrophages. It also stimulates the production of NK cells and CD4+ cells and inhibits CD8+ cells. The production and release of various cytokines from NK cells and T-helper lymphocytes also are enhanced by melatonin. Melatonin presumably regulates immune function by acting on the immune-opioid network, by affecting G protein-cAMP signal pathway and by regulating intracellular glutathione levels. Melatonin has the potential therapeutic value to enhance immune function in aged individuals and in patients in an immunocompromised state.     

Hormonal Effects on Calcium Metabolism in Crustacea

Cyclic shifts of calcium in the exoskeleton and soft tissues,as they are related to the intermolt cycle in crayfish, arereviewed. Regulatory factors, derived from the eyestalk, influencelevels of exoskeletal calcium; eyestalk extracts prepared fromanimals in premolt decrease shell calcium, while reciprocallyextracts from animals in intermolt increase it when these hormonalsources are injected into animals in the premolt stage (D₀-D₄). In addition, premolt eyestalk extract results in an increasein gastrolith calcium. In the exchange of calcium between theanimal and its environment there is evidence for differentialdepositionof recently available calcium in the exoskeleton. Further, intermoltand early premolt animals maintained in Ca⁴⁵-labelled waterfor 15 days concentrate it 4 and 3—fold in the exoskeletonand stomach, respectively. However, removal of a molt-inhibitingfactor through ablation of eyestalks results in a 20 and 40—foldincrease in incorporation inthese same sites relative to environmentalconcentrations. Treatment with mammalian parathyroid extract mobilizes bothexoskeletal and gastric calciumand leads to a rise in bloodcalcium. However, there is little or no effect on levels ofexoskeletal citric acid. Further, citric acid is higher in thecrayfish carapace during stage C, the period of mineralization,than in stage D, the period of demineralization. There are both similarities and differences between the effectsof crustacean and mammalianregulating factors with respect tothe direction and extent of mineralization. Biochemical studiesshould elucidate the mechanisms regulated by these hormones.     

The partition matrix: exploring variable phylogenetic signals along nucleotide sequence alignments

The partition matrix is a graphical tool for comparative analysis of nucleotide sequences following alignment. It is particularly useful for investigating the divergent phylogenies of sequence regions undergoing reticulate evolution. A partition matrix is generated by determining the consistency of the parsimoniously informative sites in a set of aligned sequences with the binary partitions inferred from the sequences. Since the linear order of sites is maintained, the matrix can be used to assess whether the distribution of sites either supporting or conflicting with particular partitions changes along the length of the alignment. The usefulness of the matrix in allowing visual identification of differences in evolutionary history among regions depends on the order in which partitions are shown; several suitable ordering schemes are proposed. We demonstrate the use of the partition matrix in interpreting the evolution of the pseudoautosomal boundary region on the sex chromosome of catarrhine primates. Its routine use should help to avoid attempts to derive single phylogenies from sequences whose evolution has been reticulate and to identify the gene conversion or recombination events underlying the reticulation. The method is relatively fast. It is exploratory, and it can form the basis for more formal analysis, which we discuss.      

Positive selection and sequence rearrangements generate extensive polymorphism in the gamete recognition protein bindin

Bindin is a gamete recognition protein of sea urchins that mediates species-specific attachment of sperm to an egg-surface receptor during fertilization. Sequences of bindin from closely related urchins show fixed species-specific differences. Within species, highly polymorphic bindin alleles result from point substitution, insertion/deletion, and recombination. Since speciation, positive selection favoring allelic variants has generated diversity in bindin polypeptides. Intraspecific bindin variation can be tolerated by the egg receptor, which suggests functional parallels between this system and other flexible recognition systems, including immune recognition. These results show that polymorphism in mate recognition loci required for rapid evolution of sexual isolation can arise within natural populations.      

Exploring the Functional Complementation between Grp94 and Hsp90

Grp94 and Hsp90 are the ER and cytoplasmic paralog members, respectively, of the hsp90 family of molecular chaperones. The structural and biochemical differences between Hsp90 and Grp94 that allow each paralog to efficiently chaperone its particular set of clients are poorly understood. The two paralogs exhibit a high degree of sequence similarity, yet also display significant differences in their quaternary conformations and ATPase activity. In order to identify the structural elements that distinguish Grp94 from Hsp90, we characterized the similarities and differences between the two proteins by testing the ability of Hsp90/Grp94 chimeras to functionally substitute for the wild-type chaperones in vivo. We show that the N-terminal domain or the combination of the second lobe of the Middle domain plus the C-terminal domain of Grp94 can functionally substitute for their yeast Hsp90 counterparts but that the equivalent Hsp90 domains cannot functionally replace their counterparts in Grp94. These results also identify the interface between the Middle and C-terminal domains as an important structural unit within the Hsp90 family.     

Cytogenetic studies in Eigenmannia virescens (Sternopygidae, Gymnotiformes) and new inferences on the origin of sex chromosomes in the Eigenmannia genus

Background

Previous studies suggested that multiple domestication events in South and South-East Asia (Yunnan and surrounding areas) and India have led to the genesis of modern domestic chickens. Ha Giang province is a northern Vietnamese region, where local chickens, such as the H'mong breed, and wild junglefowl coexist. The assumption was made that hybridisation between wild junglefowl and Ha Giang chickens may have occurred and led to the high genetic diversity previously observed. The objectives of this study were i) to clarify the genetic structure of the chicken population within the Ha Giang province and ii) to give evidence of admixture with G. gallus. A large survey of the molecular polymorphism for 18 microsatellite markers was conducted on 1082 chickens from 30 communes of the Ha Giang province (HG chickens). This dataset was combined with a previous dataset of Asian breeds, commercial lines and samples of Red junglefowl from Thailand and Vietnam (Ha Noï). Measurements of genetic diversity were estimated both within-population and between populations, and a step-by-step Bayesian approach was performed on the global data set.

Results

The highest value for expected heterozygosity (> 0.60) was found in HG chickens and in the wild junglefowl populations from Thailand. HG chickens exhibited the highest allelic richness (mean A = 2.9). No significant genetic subdivisions of the chicken population within the Ha Giang province were found. As compared to other breeds, HG chickens clustered with wild populations. Furthermore, the neighbornet tree and the Bayesian clustering analysis showed that chickens from 4 communes were closely related to the wild ones and showed an admixture pattern.

Conclusion

In the absence of any population structuring within the province, the H'mong chicken, identified from its black phenotype, shared a common gene pool with other chickens from the Ha Giang population. The large number of alleles shared exclusively between Ha Giang chickens and junglefowl, as well as the results of a Bayesian clustering analysis, suggest that gene flow has been taking place from junglefowl to Ha Giang chickens.     

A male patient from the West Indies with invasive ductal carcinoma in the right breast: A case report and literature review

Background: Men with breast carcinoma have a poor prognosis, especially in the younger age group (30–40 years of age), because most breast enlargements in young men are dismissed as gynecomastia, resulting in an unnecessary delay in treatment.Objective: We describe the case of a young male patient with invasive ductal breast carcinoma.Case summary: In November 2005, a 30-year-old Afro-Caribbean man presented at St. Clair Medical Centre in Port of Spain, Trinidad, with a painless lump in the right breast. Diagnostic findings revealed that the patient had stage II invasive ductal carcinoma, for which he underwent a mastectomy with total axillary clearance.Conclusion: Surgeons investigating unilateral breast swellings in young males should not dismiss them simply as gynecomastia, and should be wary of cancer.     

Breastfeeding practices of ethnic Indian immigrant women in Melbourne,Australia

Background

The health benefits of breastfeeding are well documented in public health and medical literature worldwide. Despite this, global rates of breastfeeding steadily decline during the first couple of months postpartum. Although immigrant women have higher initiation rates and a longer duration of breastfeeding overall, breastfeeding practices are compromised because of a myriad of socioeconomic and cultural factors, including the acculturation process. The objective of this study was to show how acculturation and cultural identity influenced breastfeeding practices among Indian immigrants in Melbourne, Australia.

Methods

Twelve case studies were employed to gather narratives of women’s lived experiences. Ethnographic field research methods were used to collect data, including participant observation, semi-structured interviews, case studies, and life histories. This provided in-depth information from women on various aspects of the immigrant experience of motherhood, including infant care and feeding. Participants were opportunistically recruited from Indian obstetricians and gynaecologists. Women identifying as ethnic Indian and in their third trimester of pregnancy were recruited. Interviews were conducted in women’s homes in metropolitan Melbourne over a 12 month period between 2004 and 2005. Data were coded and analysed thematically.

Results

All women identified as ethnic Indian and initiated breastfeeding in accordance with their cultural identity. Social support and cultural connectivity impacted positively on duration of breastfeeding. However, acculturation (adopting Australian cultural values and gender norms, including returning to paid employment) negatively influenced breastfeeding duration. In addition, the high reliance of recent immigrants on the advice of healthcare professionals who gave inconsistent advice negatively affected exclusive breastfeeding.

Conclusions

For ethnic Indian immigrant women breastfeeding practice is closely linked to acculturation and identity construction, both personal and communal. The lack of social and cultural networks for recent immigrants prevents their involvement in the cultural systems that traditionally support breastfeeding. With this in mind, healthcare professionals should deliver services in a culturally appropriate and sensitive manner where women feel supported as well as empowered.