Young Children’s Sensitivity to Their Own Ignorance in Informing Others

Prior research suggests that young children selectively inform others depending on others’ knowledge states. Yet, little is known whether children selectively inform others depending on their own knowledge states. To explore this issue, we manipulated 3- to 4-year-old children’s knowledge about the content of a box and assessed the impact on their decisions to inform another person. Moreover, we assessed the presence of uncertainty gestures while they inform another person in light of the suggestions that children''s gestures reflect early developing, perhaps transient, epistemic sensitivity. Finally, we compared children’s performance in the informing context to their explicit verbal judgment of their knowledge states to further confirm the existence of a performance gap between the two tasks. In their decisions to inform, children tend to accurately assess their ignorance, whereas they tend to overestimate their own knowledge states when asked to explicitly report them. Moreover, children display different levels of uncertainty gestures depending on the varying degrees of their informational access. These findings suggest that children’s implicit awareness of their own ignorance may be facilitated in a social, communicative context.     

Discovery and synthesis of tetrahydropyrimidinedione-4-carboxamides as endothelial lipase inhibitors

Endothelial lipase (EL) inhibitors have been shown to elevate HDL-C levels in pre-clinical murine models and have potential benefit in prevention and treatment of cardiovascular diseases. Modification of the 1-ethyl-3-hydroxy-1,5-dihydro-2H-pyrrol-2-one (DHP) lead, 1, led to the discovery of a series of potent tetrahydropyrimidinedione (THP) EL inhibitors. Synthesis and SAR studies including modification of the amide group, together with changes on the pyrimidinone core led to a series of arylcycloalkyl, indanyl, and tetralinyl substituted 5-amino or 5-hydroxypyrimidinedione-4-carboxamides. Several compounds were advanced to PK evaluation. Among them, compound 4a was one of the most potent with measurable EL_HDL hSerum potency and compound 3g demonstrated the best overall pharmacokinetic parameters.     

Cytosine Arabinoside Induces Apoptosis in Cerebellar Neurons in Culture

Abstract: Cytosine arabinoside (AraC) is a pyrimidine antimetabolite that prevents cell proliferation by inhibiting DNA synthesis. We report that AraC kills cultured cerebellar neurons in a concentration-dependent fashion with an EC₅₀ of ∼60 µ M when added shortly after seeding. This cell death has apoptotic features because we observed (1) morphology of apoptotic nuclei as judged by DNA staining with Hoechst 33258, (2) DNA fragmentation with typical ladder pattern on agarose gel, (3) positive nuclear labeling with a specific in situ DNA fragmentation staining, (4) prevention by deoxycytidine (IC₅₀ = 1 µ M ), protein, and RNA synthesis inhibitors, and (5) release of DNA fragments in the incubating medium. We have also observed that several proteins were overexpressed in AraC-treated neurons by two-dimensional polyacrylamide gel electrophoresis. We conclude that AraC induces a signal that triggers a cascade of new mRNA and protein synthesis, leading to apoptotic cell death in cultured cerebellar granule cells.     

A Contiguous Clone Map over 3 Mb on the Long Arm of Chromosome 11 across a Balanced Translocation Associated with Schizophrenia

Forty-nine clones derived by microdissection of a schizophrenia-associated t(1;11)(q42.1;q14.3) breakpoint region have been assigned by somatic cell hybrid mapping to seven discrete intervals on the long arm of human chromosome 11. Eleven of the clones were shown to map to a small region immediately distal to the translocation breakpoint on 11q.A 3-Mb contiguous clone map of this region was established by isolation of corresponding YAC recombinants. The contig was oriented and shown to traverse the translocation breakpoint by FISH and microsatellite marker analysis. This contig will facilitate the isolation of candidate sequences whose expression may be affected by the translocation.     

Degradation and racemization of zopiclone enantiomers in plasma and partially aqueous solutions

We investigated the degradation and racemization of zopiclone (ZOP) enantiomers in plasma and partially aqueous solutions (ethanol:phosphate buffer). Degradation and racemization increased with increasing pH and temperature. Degradation products were identified by means of mass spectrometry, which revealed hydrolysis of the carbamate function and opening of the pyrrolidone ring. In plasma, neither degradation nor racemization occurred after 6 months of storage at -20°C and subsequent extraction. © 1995 Wiley-Liss, Inc.     

Azurocidin, a Natural Antibiotic from Human Neutrophils: Expression, Antimicrobial Activity, and Secretion

The azurophil granules of human PMN contain four antibiotic proteins, the serprocidins, which have extensive homology to one another and to serine proteases. Azurocidin, a member of this family, is a 29-kDa glycoprotein with broad spectrum antimicrobial activity and chemotactic activity toward monocytes. Insect cells transfected with a baculovirus vector carrying azurocidin cDNA produced a recombinant azurocidin protein. We purified the recombinant azurocidin protein from the culture medium of the infected cells and showed that it retained the antimicrobial activity of the native neutrophil-derived molecule. In addition, we present evidence that a 49-amino-acid region of the recombinant azurocidin protein is required for its secretion from insect cells.     

Pet Loss and Grief: Identifying At-risk Pet Owners during the Euthanasia Process

Pet owners often experience complex and profound grief reactions when their animals are euthanized. Veterinary staff are increasingly being called upon to be aware of and to respond to the grief reactions of pet owners at this critical time. The objectives of this study were to identify pet owners who are most at risk of grief and to suggest veterinary interventions during the euthanasia process. A convenience sample of 409 pet owners whose animals had been euthanized in the past year took part in a survey. Variables of interest included pet and pet-owner demographics, pet-death characteristics, attachment to pet, and bereavement reactions. Stepwise multiple regression analyses were conducted to identify factors related to the three grief reaction subtypes: sorrow, anger, and guilt. Results indicated that attachment to pets was a strong predictor of feelings of grief/sorrow (p < 0.001) and anger (p < 0.001). Sudden death was also related to feelings of anger (p < 0.05). Cancer diagnosis was negatively related to feelings of anger (p < 0.05) and guilt (p < 0.01). The findings from this study provide additional insight into the complexity of grief following pet euthanasia. For veterinary staff, anticipating the needs of pet owners and supporting them through the grief process is an integral role. Understanding which pet owners are at greatest risk of grief is an important initial step, followed by empathic communications, sensitive interactions, and the provision of grief support.     

Adaptation to climate through flowering phenology: a case study in Medicago truncatula

Local climatic conditions likely constitute an important selective pressure on genes underlying important fitness‐related traits such as flowering time, and in many species, flowering phenology and climatic gradients strongly covary. To test whether climate shapes the genetic variation on flowering time genes and to identify candidate flowering genes involved in the adaptation to environmental heterogeneity, we used a large Medicago truncatula core collection to examine the association between nucleotide polymorphisms at 224 candidate genes and both climate variables and flowering phenotypes. Unlike genome‐wide studies, candidate gene approaches are expected to enrich for the number of meaningful trait associations because they specifically target genes that are known to affect the trait of interest. We found that flowering time mediates adaptation to climatic conditions mainly by variation at genes located upstream in the flowering pathways, close to the environmental stimuli. Variables related to the annual precipitation regime reflected selective constraints on flowering time genes better than the other variables tested (temperature, altitude, latitude or longitude). By comparing phenotype and climate associations, we identified 12 flowering genes as the most promising candidates responsible for phenological adaptation to climate. Four of these genes were located in the known flowering time QTL region on chromosome 7. However, climate and flowering associations also highlighted largely distinct gene sets, suggesting different genetic architectures for adaptation to climate and flowering onset.     

A partial metabolic pathway enables group b streptococcus to overcome quinone deficiency in a host bacterial community

Aerobic respiration metabolism in Group B Streptococcus (GBS) is activated by exogenous heme and menaquinone. This capacity enhances resistance of GBS to acid and oxidative stress and improves its survival. In this work, we discovered that GBS is able to respire in the presence of heme and 1,4‐dihydroxy‐2‐naphthoic acid (DHNA). DHNA is a biosynthetic precursor of demethylmenaquinone (DMK) in many bacterial species. A GBS gene (gbs1789) encodes a homolog of the MenA 1,4‐dihydroxy‐2‐naphthoate prenyltransferase enzyme, involved in the synthesis of demethylmenaquinone. In this study, we showed that gbs1789 is involved in the biosynthesis of long‐chain demethylmenaquinones (DMK‐10). The Δ gbs1789 mutant cannot respire in the presence of heme and DHNA, indicating that endogenously synthesized DMKs are cofactors of the GBS respiratory chain. We also found that isoprenoid side chains from GBS DMKs are produced by the protein encoded by the gbs1783 gene, since this gene can complement an Escherichia coli ispB mutant defective for isoprenoids chain synthesis. In the gut or vaginal microbiote, where interspecies metabolite exchanges occur, this partial DMK biosynthetic pathway can be important for GBS respiration and survival in different niches.