Impaired Knowledge of Driving Laws Is Associated with Recommended Driving Cessation in Cognitively Impaired Older Adults

Background/Aims: The present study examined if knowledge of driving laws independently predicts on-the-road driving performance among cognitively impaired older adults. Methods: The current study consisted of retrospective observational analyses on 55 cognitively impaired older adults (77.9 ± 6.4 years) that completed an on-the-road driving evaluation, a 20-item knowledge test of driving laws, and a brief cognitive test battery. Results: Logistic regression found poorer performance on the knowledge test was significantly associated with greater likelihood of recommended driving cessation beyond important demographic and cognitive variables (p Conclusion: Cognitively impaired patients’ ability to drive may be related to their knowledge regarding common driving laws, in addition to their current level of cognitive functioning

Genomic HIV RNA Induces Innate Immune Responses through RIG-I-Dependent Sensing of Secondary-Structured RNA

Contains fulltext : 108031.pdf (publisher's version ) (Open Access)BACKGROUND: Innate immune responses have recently been appreciated to play an important role in the pathogenesis of HIV infection. Whereas inadequate innate immune sensing of HIV during acute infection may contribute to failure to control and eradicate infection, persistent inflammatory responses later during infection contribute in driving chronic immune activation and development of immunodeficiency. However, knowledge on specific HIV PAMPs and cellular PRRs responsible for inducing innate immune responses remains sparse. METHODS/PRINCIPAL FINDINGS: Here we demonstrate a major role for RIG-I and the adaptor protein MAVS in induction of innate immune responses to HIV genomic RNA. We found that secondary structured HIV-derived RNAs induced a response similar to genomic RNA. In primary human peripheral blood mononuclear cells and primary human macrophages, HIV RNA induced expression of IFN-stimulated genes, whereas only low levels of type I IFN and tumor necrosis factor alpha were produced. Furthermore, secondary structured HIV-derived RNA activated pathways to NF-kappaB, MAP kinases, and IRF3 and co-localized with peroxisomes, suggesting a role for this organelle in RIG-I-mediated innate immune sensing of HIV RNA. CONCLUSIONS/SIGNIFICANCE: These results establish RIG-I as an innate immune sensor of cytosolic HIV genomic RNA with secondary structure, thereby expanding current knowledge on HIV molecules capable of stimulating the innate immune system

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Rotational Cropping Systems for Nitrogen Management and Weed Control in Dryland Organic Wheat Production

Diversification of cropping systems with legumes is a common practice used to overcome soil fertility and weed control challenges in organic farming systems. The current study assessed different legume-intensive cropping systems with the potential to minimize management risks for dryland, organic wheat growers in the Inland Pacific Northwest region of the United States. Several cropping systems ranged from cereal-intensive cash crops to legume-intensive green manure and forage, and were grown for the three-year transition period prior to organic certification. The goal was to identify systems that would produce high quality, certified organic wheat. All cropping systems that included a legume for at least one year during the transition phase improved soil inorganic nitrogen (N) levels, but systems that included legumes for the duration of the transition also reduced weeds as a result of repeated mowing. Weed control is as great of a concern as soil N for producing organic wheat and in this study, reduced weed pressure improved wheat yield and protein levels throughout the transition and into organic production. Intercropping a legume cover crop with wheat was used as an additional method to improve soil inorganic N. Competition for soil moisture stress was not a concern, and although N from the legumes was not immediately available to the growing wheat crop, intercropped legume and wheat systems could be grown in rotation with other crops for soil management and weed control. Mechanical removal of the intercrop with a precision inter-row cultivator was a useful crop control method and offered opportunities for further research on cover crop and weed management. Using competitive cultivars and crop-types was also necessary. Intensive management of legumes as intercrops, cover crops, and forage demonstrated the potential to greatly improve organic winter wheat production. However, supplemental soil nutrient sources would need to be added in addition to legumes in order to sustain organic wheat production over time. Organic production of dryland wheat is possible but complex management strategies must be consistent and focus on weed control as much as soil fertility

Nuclear Pore Complex Function in Saccharomyces cerevisiae Is Influenced by Glycosylation of the Transmembrane Nucleoporin Pom152p

The regulated transport of proteins across the nuclear envelope occurs through nuclear pore complexes (NPCs), which are composed of >30 different protein subunits termed nucleoporins. While some nucleoporins are glycosylated, little about the role of glycosylation in NPC activity is understood. We have identified loss-of-function alleles of ALG12, encoding a mannosyltransferase, as suppressors of a temperature-sensitive mutation in the gene encoding the FXFG-nucleoporin NUP1. We observe that nup1Δ cells import nucleophilic proteins more efficiently when ALG12 is absent, suggesting that glycosylation may influence nuclear transport. Conditional nup1 and nup82 mutations are partially suppressed by the glycosylation inhibitor tunicamycin, while nic96 and nup116 alleles are hypersensitive to tunicamycin treatment, further implicating glycosylation in NPC function. Because Pom152p is a glycosylated, transmembrane nucleoporin, we examined genetic interactions between pom152 mutants and nup1Δ. A nup1 deletion is lethal in combination with pom152Δ, as well as with truncations of the N-terminal and transmembrane regions of Pom152p. However, truncations of the N-glycosylated, lumenal domain of Pom152p and pom152 mutants lacking N-linked glycosylation sites are viable in combination with nup1Δ, suppress nup1Δ temperature sensitivity, and partially suppress the nuclear protein import defects associated with the deletion of NUP1. These data provide compelling evidence for a role for glycosylation in influencing NPC function