Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor

Pituitary adenylate cyclase-activating polypeptide (PACAP) is known to broadly regulate the cellular stress response. In contrast, it is unclear if the PACAP-PAC1 receptor pathway has a role in human psychological stress responses, such as post-traumatic stress disorder (PTSD). Here we find, in heavily traumatized subjects, a sex-specific association of PACAP blood levels with fear physiology, PTSD diagnosis and symptoms in females. We examined 44 single nucleotide polymorphisms (SNPs) spanning the PACAP (encoded by ADCYAP1) and PAC1 (encoded by ADCYAP1R1) genes, demonstrating a sex-specific association with PTSD. A single SNP in a putative oestrogen response element within ADCYAP1R1, rs2267735, predicts PTSD diagnosis and symptoms in females only. This SNP also associates with fear discrimination and with ADCYAP1R1 messenger RNA expression in human brain. Methylation of ADCYAP1R1 in peripheral blood is also associated with PTSD. Complementing these human data, ADCYAP1R1 mRNA is induced with fear conditioning or oestrogen replacement in rodent models. These data suggest that perturbations in the PACAP-PAC1 pathway are involved in abnormal stress responses underlying PTSD. These sex-specific effects may occur via oestrogen regulation of ADCYAP1R1. PACAP levels and ADCYAP1R1 SNPs may serve as useful biomarkers to further our mechanistic understanding of PTSD.     

Loss of Siglec-14 reduces the risk of chronic obstructive pulmonary disease exacerbation

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. COPD exacerbation, or episodic worsening of symptoms, often results in hospitalization and increased mortality rates. Airway infections by new bacterial strains, such as nontypeable Haemophilus influenzae (NTHi), are a major cause of COPD exacerbation. NTHi express lipooligosaccharides that contain sialic acids, and may interact with Siglec-14, a sialic acid recognition protein on myeloid cells that serves as an activating signal transduction receptor. A null allele polymorphism in SIGLEC14 may attenuate the inflammatory responses to NTHi by eliminating Siglec-14 expression. We asked if the loss of Siglec-14 attenuates the inflammatory response by myeloid cells against NTHi, and if the SIGLEC14-null polymorphism has any effect on COPD exacerbation. We found that NTHi interacts with Siglec-14 to enhance proinflammatory cytokine production in a tissue culture model. Inhibitors of the Syk tyrosine kinase suppress this response. Loss of Siglec-14, due to SIGLEC14-null allele homozygosity, is associated with a reduced risk of COPD exacerbation in a Japanese patient population. Taken together, Siglec-14 and its downstream signaling pathway facilitate the “infection–inflammation–exacerbation” axis of COPD disease progression, and may represent promising targets for therapeutic intervention.     

Species composition and habitat associations of benthic algal assemblages in headwater streams of the Sierra Nevada, California

Despite their trophic importance and potential importance as bioindicators of stream condition, benthic algae have not been well studied in California. In particular there are few studies from small streams in the Sierra Nevada. The objective of this study was to determine the standing crop of chlorophyll- a and benthic algal species assemblages present in the small 1st- and 2nd-order streams of the Kings River Experimental Watersheds (KREW, watersheds of Bull, Providence, Duff, and Teakettle Creeks) and determine the associations of these measures with stream habitat. We collected samples of benthic algae from rock substrata in September 2002 (7 sites) and 2005 (the same 7 sites plus 5 additional sites). Habitat and water-quality data were collected concurrently. Chlorophyll- a values ranged from 0.2 to 3.2 mg ? m –2 . Chlorophyll- a in the Bull Creek watershed was generally lower than in the other watersheds. Benthic algal assemblages were dominated by diatoms and cyanobacteria. We collected 79 taxa of diatoms in 2002 and 126 taxa in 2005. Diatom taxa richness in individual samples ranged from 15 to 47. Nonmetric multidimensional scaling analysis of arcsine square-root transformed proportional abundances of diatoms identified 3 groups of sites. Bull Creek sites were generally different from other sites (group 1), and the sites from Bull Creek were different in 2002 (group 2) and 2005 (group 3). Five taxa appeared to be particularly important in distinguishing groups: Achnanthidium minutissimum , Cocconeis placentula , Eunotia incise , Eunotia pectinalis var. minor , and Planothidium lanceolatum . Elevation, water temperature, pH, specific conductance, and canopy were habitat variables correlated with the differences in diatom assemblages among sites. Our results provide a valuable baseline for future studies of benthic algae in Sierra Nevada headwater streams and will be particularly important in understanding the effects of different forest restoration management strategies being tested in the KREW project.     

Epidemiological parameters of HIV transmission

Epidemiological data on the main determinants of the transmission potential of HIV-1 in specific at risk groups in slowly accumulating, but many uncertainties remain.     

Possible demographic consequences of AIDS in developing countries

Simple mathematical models of the transmission dynamics of HIV that incorporate demographic and epidemiological processes to assess the potential impact of AIDS on human population growth and structure in developing countries suggest that AIDS is capable of changing population growth rates from positive to negative values over timescales of a few decades. The disease is predicted to have little if any impact on the dependency ratio of a population, defined as the number of children below age 15 years and elderly people over 64 years, divided by the number of adults between 15 to 64 years.     

CHFR: a key checkpoint component implicated in a wide range of cancers

CHFR (Checkpoint with Forkhead-associated and RING finger domains) has been implicated in a checkpoint regulating entry into mitosis. However, the details underlying its roles and regulation are unclear due to conflicting lines of evidence supporting different notions of its functions. We provide here an overview of how CHFR is thought to contribute towards regulating mitotic entry and present possible explanations for contradictory observations published on the functions and regulation of CHFR. Furthermore, we survey key data showing correlations between promoter hypermethylation or down-regulation of CHFR and cancers, with a view on the likely reasons why different extents of correlations have been reported. Lastly, we explore the possibilities of exploiting CHFR promoter hypermethylation status in diagnostics and therapeutics for cancer patients. With keen interest currently focused on the association between hypermethylation of CHFR and cancers, details of how CHFR functions require further study to reveal how its absence might possibly contribute to tumorigenesis.