Do plants contain g protein-coupled receptors?

Whether G protein-coupled receptors (GPCRs) exist in plants is a fundamental biological question. Interest in deorphanizing new GPCRs arises because of their importance in signaling. Within plants, this is controversial, as genome analysis has identified 56 putative GPCRs, including G protein-coupled receptor1 (GCR1), which is reportedly a remote homolog to class A, B, and E GPCRs. Of these, GCR2 is not a GPCR; more recently, it has been proposed that none are, not even GCR1. We have addressed this disparity between genome analysis and biological evidence through a structural bioinformatics study, involving fold recognition methods, from which only GCR1 emerges as a strong candidate. To further probe GCR1, we have developed a novel helix-alignment method, which has been benchmarked against the class A-class B-class F GPCR alignments. In addition, we have presented a mutually consistent set of alignments of GCR1 homologs to class A, class B, and class F GPCRs and shown that GCR1 is closer to class A and/or class B GPCRs than class A, class B, or class F GPCRs are to each other. To further probe GCR1, we have aligned transmembrane helix 3 of GCR1 to each of the six GPCR classes. Variability comparisons provide additional evidence that GCR1 homologs have the GPCR fold. From the alignments and a GCR1 comparative model, we have identified motifs that are common to GCR1, class A, B, and E GPCRs. We discuss the possibilities that emerge from this controversial evidence that GCR1 has a GPCR fold.

Exploring the efficacy of a residential treatment program incorporating cognitive processing therapy-cognitive for veterans with PTSD and traumatic brain injury.

As the numbers of military personnel participating in the wars in Afghanistan and Iraq continue to grow, the percentage of individuals who return with both a traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) also increases. Although there appears to be significant overlap in the symptoms resulting from PTSD and TBI, the best course of treatment remains an area of controversy. The authors present initial findings from a Veterans Administration residential program for comorbid PTSD and TBI. Forty-two participants completed a program comprising psychoeducational groups and cognitive skill building that was augmented with a modification of standard cognitive processing therapy. The results suggest that residential programs that incorporate this form of cognitive therapy can anticipate meaningful participation from patients, and that it may be an effective approach to treat PTSD in individuals with a history of TBI.

Contaminated heparin associated with adverse clinical events and activation of the contact system.

BACKGROUND: There is an urgent need to determine whether oversulfated chondroitin sulfate (OSCS), a compound contaminating heparin supplies worldwide, is the cause of the severe anaphylactoid reactions that have occurred after intravenous heparin administration in the United States and Germany. METHODS: Heparin procured from the Food and Drug Administration, consisting of suspect lots of heparin associated with the clinical events as well as control lots of heparin, were screened in a blinded fashion both for the presence of OSCS and for any biologic activity that could potentially link the contaminant to the observed clinical adverse events. In vitro assays for the activation of the contact system and the complement cascade were performed. In addition, the ability of OSCS to recapitulate key clinical manifestations in vivo was tested in swine. RESULTS: The OSCS found in contaminated lots of unfractionated heparin, as well as a synthetically generated OSCS reference standard, directly activated the kinin-kallikrein pathway in human plasma, which can lead to the generation of bradykinin, a potent vasoactive mediator. In addition, OSCS induced generation of C3a and C5a, potent anaphylatoxins derived from complement proteins. Activation of these two pathways was unexpectedly linked and dependent on fluid-phase activation of factor XII. Screening of plasma samples from various species indicated that swine and humans are sensitive to the effects of OSCS in a similar manner. OSCS-containing heparin and synthetically derived OSCS induced hypotension associated with kallikrein activation when administered by intravenous infusion in swine. CONCLUSIONS: Our results provide a scientific rationale for a potential biologic link between the presence of OSCS in suspect lots of heparin and the observed clinical adverse events. An assay to assess the amidolytic activity of kallikrein can supplement analytic tests to protect the heparin supply chain by screening for OSCS and other highly sulfated polysaccharide contaminants of heparin that can activate the contact system.

The 4P's Plus screen for substance use in pregnancy: clinical application and outcomes.

OBJECTIVE: Determine the prevalence of substance use among pregnant women in five diverse communities utilizing the 4P's Plus screen for alcohol, tobacco, and other drug use. STUDY DESIGN: Pregnant women enrolled in prenatal care clinics in five communities were screened for substance use with the 4P's Plus. Those women with a positive screen underwent an assessment for substance use through a follow-up structured clinical interview conducted at the same prenatal visit. RESULTS: Among 7818 women in five communities, 2555 (32.7%) had a positive screen for substance use in pregnancy. Four of the communities conducted a follow-up assessment on all women with a positive screen (n = 1548). Among these women, 717 (15% of the total population) had continued use after learning of the pregnancy. Overall, 21% of the pregnant women used alcohol prior to recognition of the pregnancy, and 11% continued use after knowledge of the pregnancy. Among the 512 women who continued to use alcohol, 2% were drinking daily, 7% were drinking 3 to 6 days per week, 27% were drinking 1 to 2 days per week, and 63% were drinking less than 1 day per week. The rates of marijuana use and other illicit drug use among the women were 7 and 2%, respectively, prior to knowledge of pregnancy and dropped to 3 and 1% after learning of the pregnancy. CONCLUSION: The 4P's Plus identifies not only those pregnant women whose drinking or drug use is at a high enough level to impair daily functioning, but provides an opportunity for early intervention for the much larger group of women whose pregnancies are at risk from relatively small amounts of substance use.