Remaining Human: How the Airline Deregulation Act Shields Commercial Air Carriers From Legal Liability for Mishandling Human Remains

The Airline Deregulation Act of 1978 (ADA) deregulated the domestic airline industry. Specifically, the ADA ended the dual administrative system, which allowed the states to regulate intrastate airfare and permitted the federal government’s Civil Aeronautics Board (CAB) to regulate interstate airfare. The Act also included a broad preemption clause to prevent the states from reimposing economic regulations on air travel. The preemption clause prohibits a “State . . . [from] enact[ing] or enforc[ing] any law, rule, regulation, standard, or other provision having the force and effect of law relating to rates, routes, or services of any air carrier.” The Supreme Court has interpreted the scope of the ADA’s preemption clause expansively and concluded that only state law claims with a “tenuous, remote, or peripheral” relationship to an airline’s services survive preemption. Yet, the Supreme Court has never defined the key word: Service. Today, federal circuit courts disagree on the definition of “service,” and a majority have adopted the Fifth Circuit’s definition articulated in Hodges v. Delta Airlines, Inc. Applying the Supreme Court’s expansive view of the ADA’s preemption clause, the Fifth Circuit defined the term “service” as all bargained-for air carrier services, including “ticketing, boarding procedures, provision of food and drink, and baggage handling, in addition to the transportation itself.” The Fifth Circuit’s definition preempts almost all conceivable state law claims despite the Supreme Court excepting claims with a “tenuous, remote, or peripheral” relationship to an airline’s services from preemption. Consequently, the aviation industry largely evades state law. This Comment argues that courts should interpret the ADA’s preemption clause more narrowly to allow more state law claims to survive preemption, particularly claims arising from an airline’s mishandling, delaying, or misplacing of a loved one’s remains. As the COVID-19 pandemic claims lives and frustrates air travel, a perfect storm threatens to mishandle, delay, or misplace a loved one’s remains. Grieving mothers, fathers, husbands, and wives are left without a legal remedy because the ADA shields the airline industry from liability concerning “baggage handling” and the “transportation itself.” Courts should interpret the ADA’s preemption clause more narrowly based on the ADA’s clear purpose, the plain meaning of the ADA’s text, stare decisis, and the law’s treatment of other entities that mishandle human remains

Prenatal Dichlorodiphenyldichloroethylene (DDE) and Asthma in Children

Prevalence of asthma increases with increasing dichlorodiphenyldichloroethylene (DDE) levels. However, the effect of early-life exposure, the fundamental window of exposure, is unknown. We assessed the association between prenatal DDE and other organochlorine compounds, and atopy and asthma during infancy. All women presenting for antenatal care in Menorca (Spain) over 12 months starting in mid-1997 were invited to take part in a longitudinal study; 482 children were subsequently enrolled, and 468 (97.1%) provided complete outcome data up to the fourth year of study. Prenatal exposure of organochlorine compounds was measured in cord serum in 405 (83%) children. Asthma was defined on the basis of wheezing at 4 years of age, persistent wheezing, or doctor-diagnosed asthma. We measured specific immunoglobulin-E (IgE) against house dust mite, cat, and grass in sera extracted at 4 years of age. DDE (median = 1.03 ng/mL) was detected in all children, as well as hexachlorobenzene (0.68 ng/mL) and polychlorobiphenyls (0.69 ng/mL). Wheezing at 4 years of age increased with DDE concentration, particularly at the highest quartile [9% in the lowest quartile (< 0.57 ng/mL) vs. 19% in the highest quartile (1.90 ng/mL); relative risk = 2.63 (95% confidence interval 1.19–4.69), adjusting for maternal asthma, breast-feeding, education, social class, or other organochlorines]. The association was not modified by IgE sensitization and occurred with the same strength among nonatopic subjects and among those with persistent wheezing or diagnosed asthma. DDE was not associated with atopy alone. Prenatal exposure to DDE residues may contribute to development of asthma

Affiliative Behavior, Ultrasonic Communication and Social Reward Are Influenced by Genetic Variation in Adolescent Mice

Social approach is crucial for establishing relationships among individuals. In rodents, social approach has been studied primarily within the context of behavioral phenomena related to sexual reproduction, such as mating, territory defense and parental care. However, many forms of social interaction occur before the onset of reproductive maturity, which suggests that some processes underlying social approach among juvenile animals are probably distinct from those in adults. We conducted a longitudinal study of social investigation (SI) in mice from two inbred strains to assess the extent to which genetic factors influence the motivation for young mice to approach one another. Early-adolescent C57BL/6J (B6) mice, tested 4–6 days after weaning, investigated former cage mates to a greater degree than BALB/cJ (BALB) mice, irrespective of the sex composition within an interacting pair. This strain difference was not due to variation in maternal care, the phenotypic characteristics of stimulus mice or sensitivity to the length of isolation prior to testing, nor was it attributable to a general difference in appetitive motivation. Ultrasonic vocalization (USV) production was positively correlated with the SI responses of mice from both strains. Interestingly, several USV characteristics segregated with the genetic background of young mice, including a higher average frequency and shorter duration for the USVs emitted by B6 mice. An assessment of conditioned place preference responses indicated that there was a strain-dependent difference in the rewarding nature of social contact. As adolescent mice aged, SI responses gradually became less sensitive to genetic background and more responsive to the particular sex of individuals within an interacting pair. We have thus identified a specific, genetic influence on the motivation of early-adolescent mice to approach one another. Consistent with classical theories of motivation, which propose a functional relationship between behavioral approach and reward, our findings indicate that reward is a proximal mechanism through which genetic factors affect social motivation during early adolescence

Divergent neural and endocrine responses in wild-caught and laboratory-bred Rattus norvegicus

Although rodents have represented the most intensely studied animals in neurobiological investigations for more than a century, few studies have systematically compared neural and endocrine differences between wild rodents in their natural habitats and laboratory strains raised in traditional laboratory environments. In the current study, male and female Rattus norvegicus rats were trapped in an urban setting and compared to weight-and sex-matched conspecifics living in standard laboratory housing conditions. Brains were extracted for neural assessments and fecal boli were collected for endocrine [corticosterone and dehydroepiandrosterone (DHEA)] assays. Additionally, given their role in immune and stress functions, spleen and adrenal weights were recorded. A separate set of wild rats was trapped at a dairy farm and held in captivity for one month prior to assessments; in these animals, brains were processed but no hormone data were available. The results indicated that wild-trapped rats exhibited 31% heavier brains, including higher densities of cerebellar neurons and glial cells in the bed nucleus of the stria terminalis. The wild rats also had approximately 300% greater spleen and adrenal weights, and more than a six-fold increase in corticosterone levels than observed in laboratory rats. Further research on neurobiological variables in wild vs. lab animals will inform the extensive neurobiological knowledge base derived from laboratory investigations using selectively bred rodents in laboratory environments, knowledge that will enhance the translational value of preclinical laboratory rodent studies

Interaction Networks in Yeast Define and Enumerate the Signaling Steps of the Vertebrate Aryl Hydrocarbon Receptor

The aryl hydrocarbon receptor (AHR) is a vertebrate protein that mediates the toxic and adaptive responses to dioxins and related environmental pollutants. In an effort to better understand the details of this signal transduction pathway, we employed the yeast S. cerevisiae as a model system. Through the use of arrayed yeast strains harboring ordered deletions of open reading frames, we determined that 54 out of the 4,507 yeast genes examined significantly influence AHR signal transduction. In an effort to describe the relationship between these modifying genes, we constructed a network map based upon their known protein and genetic interactions. Monte Carlo simulations demonstrated that this network represented a description of AHR signaling that was distinct from those generated by random chance. The network map was then explored with a number of computational and experimental annotations. These analyses revealed that the AHR signaling pathway is defined by at least five distinct signaling steps that are regulated by functional modules of interacting modifiers. These modules can be described as mediating receptor folding, nuclear translocation, transcriptional activation, receptor level, and a previously undescribed nuclear step related to the receptor's Per–Arnt–Sim domain

A Role for Strain Differences in Waveforms of Ultrasonic Vocalizations during Male–Female Interaction

Male mice emit ultrasonic vocalizations (USVs) towards females during male–female interaction. It has been reported that USVs of adult male mice have the capability of attracting females. Although the waveform pattern of USVs is affected by genetic background, differences among strains with respect to USV and the effects of these differences on courtship behavior have not been analyzed fully. We analyzed USV patterns, as well as actual social behavior during USV recording, in 13 inbred mouse strains, which included laboratory and wild-derived strains. Significant effects of strain were observed for the frequency of USV emission, duration, and frequency of the waveform category. Principal component (PC) analysis showed that PC1 was related to frequency and duration, and PC2–4 were related to each waveform. In the comparison of USV patterns and behaviors among strains, wild-derived KJR mice displayed the highest scores for PC2–4, and female mice paired with KJR males did not emit rejection-related click sounds. It is assumed that the waveforms emitted by KJR males have a positive effect in male–female interaction. Therefore, we extracted waveforms in PC2–4 from the USV recordings of KJR mice to produce a sound file, "HIGH2-4". As a negative control, another sound file ("LOW2-4") was created by extracting waveforms in PC2-4 from strains with low scores for these components. In the playback experiments using these sound files, female mice were attracted to the speaker that played HIGH2-4 but not the speaker that played LOW2-4. These results highlight the role of strain differences in the waveforms of male USVs during male–female interaction. The results indicated that female mice use male USVs as information when selecting a suitable mate

Regulation of Mouse Small Heat Shock Protein αb-Crystallin Gene by Aryl Hydrocarbon Receptor

The stress-inducible small heat shock protein (shsp)/αB-crystallin gene is expressed highly in the lens and moderately in other tissues. Here we provide evidence that it is a target gene of the aryl hydrocarbon receptor (AhR) transcription factor. A sequence (−329/−323, CATGCGA) similar to the consensus xenobiotic responsive element (XRE), called here XRE-like, is present in the αBE2 region of αB-crystallin enhancer and can bind AhR in vitro and in vivo. αB-crystallin protein levels were reduced in retina, lens, cornea, heart, skeletal muscle and cultured muscle fibroblasts of AhR−/− mice; αB-crystallin mRNA levels were reduced in the eye, heart and skeletal muscle of AhR−/− mice. Increased AhR stimulated αB-crystallin expression in transfection experiments conducted in conjunction with the aryl hydrocarbon receptor nuclear translocator (ARNT) and decreased AhR reduced αB-crystallin expression. AhR effect on aB-crystallin promoter activity was cell-dependent in transfection experiments. AhR up-regulated αB-crystallin promoter activity in transfected HeLa, NIH3T3 and COS-7 cells in the absence of exogenously added ligand (TCDD), but had no effect on the αB-crystallin promoter in C2C12, CV-1 or Hepa-1 cells with or without TCDD. TCDD enhanced AhR-stimulated αB-crystallin promoter activity in transfected αTN4 cells. AhR could bind to an XRE-like site in the αB-crystallin enhancer in vitro and in vivo. Finally, site-specific mutagenesis experiments showed that the XRE-like motif was necessary for both basal and maximal AhR-induction of αB-crystallin promoter activity. Our data strongly suggest that AhR is a regulator of αB-crystallin gene expression and provide new avenues of research for the mechanism of tissue-specific αB-crystallin gene regulation under normal and physiologically stressed conditions

The Cyclic AMP Cascade Is Altered in the Fragile X Nervous System

Fragile X syndrome (FX), the most common heritable cause of mental retardation and autism, is a developmental disorder characterized by physical, cognitive, and behavioral deficits. FX results from a trinucleotide expansion mutation in the fmr1 gene that reduces levels of fragile X mental retardation protein (FMRP). Although research efforts have focused on FMRP's impact on mGluR signaling, how the loss of FMRP leads to the individual symptoms of FX is not known. Previous studies on human FX blood cells revealed alterations in the cyclic adenosine 3′, 5′-monophosphate (cAMP) cascade. We tested the hypothesis that cAMP signaling is altered in the FX nervous system using three different model systems. Induced levels of cAMP in platelets and in brains of fmr1 knockout mice are substantially reduced. Cyclic AMP induction is also significantly reduced in human FX neural cells. Furthermore, cAMP production is decreased in the heads of FX Drosophila and this defect can be rescued by reintroduction of the dfmr gene. Our results indicate that a robust defect in cAMP production in FX is conserved across species and suggest that cAMP metabolism may serve as a useful biomarker in the human disease population. Reduced cAMP induction has implications for the underlying causes of FX and autism spectrum disorders. Pharmacological agents known to modulate the cAMP cascade may be therapeutic in FX patients and can be tested in these models, thus supplementing current efforts centered on mGluR signaling

Effects of degree and timing of social housing on reversal learning and response to novel objects in dairy calves

Rodents and primates deprived of early social contact exhibit deficits in learning and behavioural flexibility. They often also exhibit apparent signs of elevated anxiety, although the relationship between these effects has not been studied. To investigate whether dairy calves are similarly affected, we first compared calves housed in standard individual pens (n = 7) to those housed in a dynamic group with access to their mothers (n = 8). All calves learned to approach the correct stimulus in a visual discrimination task. Only one individually housed calf was able to re-learn the task when the stimuli were reversed, compared to all but one calf from the group. A second experiment investigated whether this effect might be explained by anxiety in individually housed animals interfering with their learning, and tested varying degrees of social contact in addition to the complex group: pair housing beginning early (approximately 6 days old) and late (6 weeks old). Again, fewer individually reared calves learned the reversal task (2 of 10 or 20%) compared to early paired and grouped calves (16 of 21 or 76% of calves). Late paired calves had intermediate success. Individually housed calves were slower to touch novel objects, but the magnitude of the fear response did not correlate with reversal performance. We conclude that individually housed calves have learning deficits, but these deficits were not likely associated with increased anxiety

Epstein-Barr Virus LMP2A Reduces Hyperactivation Induced by LMP1 to Restore Normal B Cell Phenotype in Transgenic Mice

Epstein-Barr virus (EBV) latently infects most of the human population and is strongly associated with lymphoproliferative disorders. EBV encodes several latency proteins affecting B cell proliferation and survival, including latent membrane protein 2A (LMP2A) and the EBV oncoprotein LMP1. LMP1 and LMP2A signaling mimics CD40 and BCR signaling, respectively, and has been proposed to alter B cell functions including the ability of latently-infected B cells to access and transit the germinal center. In addition, several studies suggested a role for LMP2A modulation of LMP1 signaling in cell lines by alteration of TRAFs, signaling molecules used by LMP1. In this study, we investigated whether LMP1 and LMP2A co-expression in a transgenic mouse model alters B cell maturation and the response to antigen, and whether LMP2A modulates LMP1 function. Naïve LMP1/2A mice had similar lymphocyte populations and antibody production by flow cytometry and ELISA compared to controls. In the response to antigen, LMP2A expression in LMP1/2A animals rescued the impairment in germinal center generation promoted by LMP1. LMP1/2A animals produced high-affinity, class-switched antibody and plasma cells at levels similar to controls. In vitro, LMP1 upregulated activation markers and promoted B cell hyperproliferation, and co-expression of LMP2A restored a wild-type phenotype. By RT-PCR and immunoblot, LMP1 B cells demonstrated TRAF2 levels four-fold higher than non-transgenic controls, and co-expression of LMP2A restored TRAF2 levels to wild-type levels. No difference in TRAF3 levels was detected. While modulation of other TRAF family members remains to be assessed, normalization of the LMP1-induced B cell phenotype through LMP2A modulation of TRAF2 may be a pathway by which LMP2A controls B cell function. These findings identify an advance in the understanding of how Epstein-Barr virus can access the germinal center in vivo, a site critical for both the genesis of immunological memory and of virus-associated tumors