Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) respond to a variety of different external stimuli and activate G proteins. GPCRs share many structural ...features, including a bundle of seven transmembrane α helices connected by six loops of varying lengths. We determined the structure of rhodopsin from diffraction data extending to 2.8 angstroms resolution. The highly organized structure in the extracellular region, including a conserved disulfide bridge, forms a basis for the arrangement of the seven-helix transmembrane motif. The ground-state chromophore, 11-cis-retinal, holds the transmembrane region of the protein in the inactive conformation. Interactions of the chromophore with a cluster of key residues determine the wavelength of the maximum absorption. Changes in these interactions among rhodopsins facilitate color discrimination. Identification of a set of residues that mediate interactions between the transmembrane helices and the cytoplasmic surface, where G-protein activation occurs, also suggests a possible structural change upon photoactivation.
The Secure Base Effect (SBE) refers to a human or non-human animal’s ability to use the presence of a bonded caretaker, or other familiar stimulus, as a source of comfort that facilitates stress ...reduction and exploration in novel or stressful contexts. Recent research has shown that some pet domestic cats (Felis catus) display SBE in the presence of their human owner, a finding that could be utilized to improve cat welfare. In applied settings, cat owners are often encouraged to leave behind items holding their scent when leaving their cat in a novel location (e.g. boarding facility), so that these items can be provided to the cat if they show signs of separation distress. Although this practice has not be studied scientifically in cats, scent objects have been found to produce SBE in human research under similar conditions. Olfaction is thought to play an important role in the social behavior of domesticated cats, even in early life, as exposure to nest scent has been found to reduce stress in kittens. Thus, the possibility that owner scent might be sufficient to elicit SBE in cats is an important empirical question with applied implications. In the current study we asked whether owner scent would reduce cat anxiety when in an unfamiliar environment, and to what extent this might be related to whether the cat showed evidence of using their owner as a Secure Base. Forty-two adult cats underwent a counterbalanced Secure Base Test that examined the cat’s behavior with the owner present, without the owner present, and with a scent object present. On average, cats displayed a lower frequency of stress-related behaviors when the owner was present, providing support for the presence of SBE. However, this effect was not seen when the cat was alone with the scent object. The results of this research can be used to deepen our understanding of feline social behavior and welfare. These findings also highlight the importance of using evidence based practices to address cat anxiety in applied settings.
•Roughly half of evaluated cats exhibited the Secure Base Effect with their owner.•Cats displayed less stress behavior when in the company of their owner.•An object holding the owner’s scent did not promote the Secure Base Effect in cats.•Cats exhibited stress behavior in the presence of the scent object alone.•Allorubbing is an important reunion behavior, 83% of cats rub their owner following a separation.
Worldwide, domestic cats (Felis silvestris catus) outnumber domestic dogs (Canis familiaris). Despite cats’ success in human environments, dog social cognition has received considerably more ...scientific attention over the last several decades 1–3. A key aspect of what has been said to make dogs unique is their proclivity for forming attachment bonds, including secure attachments to humans 1,3, which could provide scaffolding for the development of human-like socio-cognitive abilities and contribute to success in human environments 3. Cats, like dogs, can be found living in social groups or solitarily, depending on early developmental factors, resource distribution, and lifetime experiences such as human interaction 1,2,4. Despite fewer studies, research suggests we may be underestimating cats’ socio-cognitive abilities 2. Here we report evidence, using behavioral criteria established in the human infant literature 5,6, that cats display distinct attachment styles toward human caregivers. Evidence that cats share social traits once attributed to dogs and humans alone would suggest that broader non-canine-specific mechanisms may be needed to explain cross-species attachment and socio-cognitive abilities.
Human infants and dogs display a similar capacity for the formation of secure and insecure attachment bonds with human caregivers. Vitale et al. report that cats exhibit the same distinct attachment styles toward their caregiver, including secure attachments. This widespread bonding mechanism appears to have been adapted for success in human homes.
Lameness in sheep is a global health, welfare and economic concern. White line disease (WLD), also known as shelly hoof, is a prevalent, non-infectious cause of lameness, characterised by the ...breakdown of the white line. Little is known about the predisposing factors, nor the individual disease dynamics over time. Our exploratory study aimed to investigate the prevalence and temporal dynamics of WLD, and the associated risk factors. Feet of 400 ewes from four UK commercial sheep farms were inspected for WLD at four time points across 12 months. The change in WLD state at foot-level (develop or recover) was calculated for three transition periods. We present WLD to be widespread, affecting 46.8% of foot-level and 76.6% of sheep-level observations. States in WLD changed over time, with feet readily developing and recovering from WLD within the study period. The presence of WLD at foot-level, the number of feet affected at sheep-level and dynamics in development and recovery were driven by a variety of foot-, sheep- and farm-level factors. We provide key insight into the multifaceted aetiology of WLD and corroborate previous studies demonstrating its multifactorial nature. Our study highlights an opportunity to reduce WLD prevalence and informs hypotheses for future prospective studies.
Lameness in sheep continues to be a global health, welfare and economic concern. Damaged, misshapen or overgrown feet have the potential to cause lameness either directly, or indirectly. There is a ...lack of understanding of the predisposing factors for different hoof conformation traits in sheep. Our exploratory study aimed to investigate the prevalence of, and risk factors for, three distinct hoof conformation traits relating to the sole and heel, hoof wall, and hoof wall overgrowth. Feet of 400 ewes from four UK commercial sheep farms were inspected at four time points across 12 months. For each conformation trait, a four-point ordinal system was used to score each individual claw, and foot-level scores were calculated. We present 92.4% of foot-level observations to be affected by ≥1 conformation traits. Whilst hoof conformation traits were correlated to some degree, a unique set of sheep-, foot- and farm-level factors were associated with each distinct conformation trait. We provide, for the first time, key insight into the multifaceted and multifactorial aetiology of hoof conformation in sheep, building upon previous landmark studies. Our results inform hypotheses for future prospective studies investigating the risk factors for adverse hoof conformation in sheep.
Approximately 60% of hepatitis A virus infections in Germany occur in persons without a travel history to disease-endemic areas and for whom sources of infection are unknown. Recommendation of ...pretravel vaccination fails to prevent the remaining imported infections. Using enhanced surveillance in 2007-2008, we analyzed epidemiologic patterns of hepatitis A in Germany and appropriateness and adequacy of current immunization recommendations. Young patients with a migration background who had visited friends and family in their ancestral countries accounted for most imported cases. Phylogenetic analysis showed high diversity of sequence data and clustering of strains with similar regions of origin or patient migration backgrounds. Virologic findings are compatible with those of low-incidence countries, where virtually all infections are directly or indirectly imported from other regions. Germans with a migration background are seen as a special risk group so far insufficiently reached by pretravel vaccination advice.
We report the x-ray crystal structure of human topoisomerase I covalently joined to double-stranded DNA and bound to the clinically approved anticancer agent Topotecan. Topotecan mimics a DNA base ...pair and binds at the site of DNA cleavage by intercalating between the upstream (-1) and downstream (+1) base pairs. Intercalation displaces the downstream DNA, thus preventing religation of the cleaved strand. By specifically binding to the enzyme-substrate complex, Topotecan acts as an uncompetitive inhibitor. The structure can explain several of the known structure-activity relationships of the camptothecin family of anticancer drugs and suggests that there are at least two classes of mutations that can produce a drug-resistant enzyme. The first class includes changes to residues that contribute to direct interactions with the drug, whereas a second class would alter interactions with the DNA and thereby destabilize the drug-binding site.
Dichelobacter nodosus is the causal agent of ovine footrot, a contagious disease of welfare and economic concern worldwide. Damaged feet may be subclinical carriers of D. nodosus and covertly spread ...infection. Accordingly, we evaluated the risk of misshapen and damaged feet on D. nodosus presence and load in four commercial UK sheep flocks. Foot-level observations and swabs (n = 972) were collected from ewes (n = 85) over 12 months. On average, ewes were sampled three times. Feet were inspected for disease and scored (good/poor) for three hoof conformation traits (sole and heel, wall, and wall overgrowth). Swabs were analysed for presence and load of D. nodosus, and mixed models were constructed. Poor hoof conformation traits were present in 92.5% of foot-level observations. Feet with poor sole and heel conformation were more likely to have higher D. nodosus loads (β = 0.19, 95% CI: 0.04–0.35) than those with good conformation. Furthermore, on feet positive for D. nodosus, wall overgrowth was associated with higher D. nodosus loads (β = 0.27, 95% CI: 0.01–0.52). Feet with aspects of poor conformation covertly harbour D. nodosus and are a source of infection. Flock management should be guided by hoof conformation to reduce disease challenge.
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