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NF-κB proteins are well known as transcription factors important in immune system activation. In this highly conserved role, they contribute to changes in behavior in response to infection and in response to a variety of other insults and experiences. In some mammalian neurons, NF-κBs can be found at the synapse and translocate to the nucleus to alter gene expression when activated by synaptic activity. Here, we demonstrate that, in Drosophila melanogaster, NF-κB action is important both inside and outside the nucleus and that the Dif gene has segregated nuclear and non-nuclear NF-κB action into different protein isoforms. The DifA isoform is a canonical nuclear-acting NF-κB protein that enters the nucleus and is important for combating infection. The DifB variant, but not the DifA variant, is found in the central nervous system (mushroom bodies and antennal lobes). DifB does not enter the nucleus and co-localizes with a synaptic protein. In males and females, a DifB mutant alters alcohol behavioral sensitivity without an obvious effect on combating infection, whereas a DifA mutant does not affect alcohol sensitivity but compromises the immune response. These data are evidence that the non-nuclear DifB variant contributes to alcohol behavioral sensitivity by a nongenomic mechanism that diverges from the NF-κB transcriptional effects used in the peripheral immune system. Enrichment of DifB in brain regions rich in synapses and biochemical enrichment of DifB in the synaptoneurosome fraction indicates that the protein may act locally at the synapse. [ABSTRACT FROM AUTHOR]

Analysis of intergenerational academic aspirations of Mexican-American females reveals that the mother plays a crucial role in the educational success of the daughters through total encouragement. The high level of academic aspiration in mothers is related to the achievement of the daughters and therefore create positive perceptions about maternal support, for aspiration and the perception of education's role, in the daughters' minds.

Background: N‐methyl‐D‐aspartate (NMDA) receptors regulate synaptic plasticity and modulate a wide variety of behaviors. Mammalian NMDA receptors are inhibited by ethanol (EtOH) even at low concentrations. In mice, the F639A mutation in transmembrane domain (TMD) 3 of the NR1 subunit reduces EtOH sensitivity of the receptor and, in some paradigms, reduces behavioral EtOH sensitivity and increases EtOH consumption. We tested the fly equivalent of the F639A and K544Q mutations for effects on EtOH sensitivity. Drosophila shows a high degree of behavioral and mechanistic conservation in its responses to EtOH. Methods: Homologous recombination and CRISPR/Cas9 genome editing were used to generate amino acid changes in the Drosophila NMDAR1 gene, yielding F654A and K558Q alleles. Animals were tested for the degree of EtOH sensitivity, the ability to acquire tolerance to EtOH, EtOH drinking preference, circadian rhythmicity, learning, and locomotor defects. Results: We observed that mutating the NMDAR1 channel also reduces EtOH sensitivity in adult flies. However, in flies, it was the K558Q mutation (orthologous to K544Q in mice) that reduces EtOH sensitivity in a recovery‐from‐sedation assay. The effects of the F654A mutation (orthologous to F639A in mice) were substantially different in flies than in mammals. In flies, F654A mutation produces phenotypes opposite those in mammals. In flies, the mutant allele is homozygous viable, does not seem to affect health, and increases EtOH sensitivity. Both mutations increased feeding but did not alter the animal's preference for 5% EtOH food. F654A depressed circadian rhythmicity and the capacity of males to court, but it did not depress the capacity for associative learning. K554Q, on the other hand, has little effect on circadian rhythmicity, only slightly suppresses male courtship, and is a strong learning mutant. Conclusions: Mutations in TMD 3 and in the extracellular‐vestibule calcium‐binding site of the NR1 NMDA subunit affect EtOH sensitivity in Drosophila. [ABSTRACT FROM AUTHOR]

CASE DESCRIPTION A 13-month-old castrated male cat was evaluated for a large, spontaneously developed cutaneous laceration over the left scapular region. The cat had a history of severe gingivostomatitis, conjunctivitis, giardiasis, and feline herpesvirus infection and had received systemic glucocorticoid treatment for 7 weeks prior to evaluation. CLINICAL FINDINGS Physical examination revealed a 10 × 7-cm full-thickness cutaneous laceration over the left scapular region, extremely thin skin, crusts over the dorsal aspect of the neck and base of the skull, medially curling pinnae, and moderate gingivostomatitis. TREATMENT AND OUTCOME Staged wound closure was performed with a combination of daily wound cleaning and debridement, tension and appositional sutures, and wet-to-dry and nonadherent dressings initially with a bacitracin, neomycin, and polymyxin B ointment and then with a 30:1 mixture of silver sulfadiazine and insulin. Multiple additional lesions developed and were treated in the same manner. Complete closure and resolution of all cutaneous lesions was achieved in 9 weeks. CLINICAL RELEVANCE Cats are fairly resistant to the adverse effects of glucocorticoid treatment, and iatrogenic hyperadrenocorticism is rarely reported. This case demonstrated that acquired skin fragility syndrome secondary to iatrogenic hyperadrenocorticism can develop following short-term systemic glucocorticoid administration and that large cutaneous wounds associated with this condition can be successfully managed and closed by means of the reported methods. The prognosis for skin recovery in cats with acquired skin fragility syndrome may be more favorable than previously reported. [ABSTRACT FROM AUTHOR]

Homeostatic neural adaptations to alcohol underlie the production of alcohol tolerance and the associated symptoms of withdrawal. These adaptations have been shown to persist for relatively long periods of time and are believed to be of central importance in promoting the addictive state. In Drosophila, a single exposure to alcohol results in long-lasting alcohol tolerance and symptoms of withdrawal following alcohol clearance. These persistent adaptations involve mechanisms such as long-lasting changes in gene expression and perhaps epigenetic restructuring of chromosomal regions. Histone modifications have emerged as important modulators of gene expression and are thought to orchestrate and maintain the expression of multi-gene networks. Previously genes that contribute to tolerance were identified as those that show alcohol-induced changes in histone H4 acetylation following a single alcohol exposure. However, the molecular mediator of the acetylation process that orchestrates their expression remains unknown. Here we show that the Drosophila ortholog of mammalian CBP, nejire, is the histone acetyltransferase involved in regulatory changes producing tolerance--alcohol induces nejire expression, nejire mutations suppress tolerance, and transgenic nejire induction mimics tolerance in alcohol-naive animals. Moreover, we observed that a loss-of-function mutation in the alcohol tolerance gene slo epistatically suppresses the effects of CBP induction on alcohol resistance, linking nejire to a well-established alcohol tolerance gene network. We propose that CBP is a central regulator of the network of genes underlying an alcohol adaptation. [ABSTRACT FROM AUTHOR]

Sustained or repeated exposure to sedating drugs, such as alcohol, triggers homeostatic adaptations in the brain that lead to the development of drug tolerance and dependence. These adaptations involve long-term changes in the transcription of drug-responsive genes as well as an epigenetic restructuring of chromosomal regions that is thought to signal and maintain the altered transcriptional state. Alcohol-induced epigenetic changes have been shown to be important in the long-term adaptation that leads to alcohol tolerance and dependence endophenotypes. A major constraint impeding progress is that alcohol produces a surfeit of changes in gene expression, most of which may not make any meaningful contribution to the ethanol response under study. Here we used a novel genomic epigenetic approach to find genes relevant for functional alcohol tolerance by exploiting the commonalities of two chemically distinct alcohols. In Drosophila melanogaster, ethanol and benzyl alcohol induce mutual cross-tolerance, indicating that they share a common mechanism for producing tolerance. We surveyed the genome-wide changes in histone acetylation that occur in response to these drugs. Each drug induces modifications in a large number of genes. The genes that respond similarly to either treatment, however, represent a subgroup enriched for genes important for the common tolerance response. Genes were functionally tested for behavioral tolerance to the sedative effects of ethanol and benzyl alcohol using mutant and inducible RNAi stocks. We identified a network of genes that are essential for the development of tolerance to sedation by alcohol. [ABSTRACT FROM AUTHOR]

One of the most widely studied ultimate carcinogens, 7r,8t-dihydroxy-9t, 10t-oxy-7,8,9,10-tetrahydrobenzo[]pyrene (BPDE-I), is fairly stable in organic solvents but hydrolyses rapidly in the presence of water. Routine use of BPDE-I stock solutions involves multiple cycles of warming to room temperature and return to freezer temperature and results in some decomposition of the stock with time, presumably due to uptake of water from the atmosphere. We present a simple spectrophotometric assay which allows an investigator to quickly and safely estimate the extent of such decomposition to an accuracy of ±6%. The assay is based on the rapid reaction of BPDE-I with β-mercaptoethanol in alkaline solution resulting in an adduct which exhibits a significant red-shift in the absorption spectrum. [ABSTRACT FROM PUBLISHER]