Agrochemicals represent prominent anthropogenic stressors contributing to the ongoing global insect decline. While their impact is generally assessed in terms of mortality rates, non-lethal effects ...on fitness are equally important to insect conservation. Glyphosate, a commonly used herbicide, is toxic to many animal species, and thought to impact a range of physiological functions. In this study, we investigate the impact of long-term exposure to glyphosate on locomotion, phototaxis and learning abilities in bumblebees, using a fully automated high-throughput assay. We find that glyphosate exposure had a very slight and transient impact on locomotion, while leaving the phototactic drive unaffected. Glyphosate exposure also reduced attraction towards UV light when blue was given as an alternative and, most strikingly, impaired learning of aversive stimuli. Thus, glyphosate had specific actions on sensory and cognitive processes. These non-lethal perceptual and cognitive impairments likely represent a significant obstacle to foraging and predator avoidance for wild bumblebees exposed to glyphosate. Similar effects in other species could contribute to a widespread reduction in foraging efficiency across ecosystems, driven by the large-scale application of this herbicide. The high-throughput paradigm presented in this study can be adapted to investigate sublethal effects of other agrochemicals on bumblebees or other important pollinator species, opening up a critical new avenue for the study of anthropogenic stressors.
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•Bumble bee colonies were split in half and one side was chronically exposed to glyphosate.•Locomotion, phototaxis and visual learning were tested in an automated assay.•Glyphosate-treated bees did not learn to avoid a colour paired with electric shocks.•Subtle effects of glyphosate on locomotion and phototaxis were also detected.•Our high-throughput protocol could be integrated in pesticide risk assessments.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•The dopamine transporter is a phosphoprotein that is regulated by multiple signaling pathways and phosphorylation conditions.•The N-terminal domain of the transporter contains distinct sites for PKC ...and ERK dependent phosphorylation.•Phosphorylation of these sites controls multiple transporter functions and may be dysregulated in dopaminergic diseases.
The dopamine transporter (DAT) is a plasma membrane phosphoprotein that actively translocates extracellular dopamine (DA) into presynaptic neurons. The transporter is the primary mechanism for control of DA levels and subsequent neurotransmission, and is the target for abused and therapeutic drugs that exert their effects by suppressing reuptake. The transport capacity of DAT is acutely regulated by signaling systems and drug exposure, providing neurons the ability to fine-tune DA clearance in response to specific conditions. Kinase pathways play major roles in these mechanisms, and this review summarizes the current status of DAT phosphorylation characteristics and the evidence linking transporter phosphorylation to control of reuptake and other functions. Greater understanding of these processes may aid in elucidation of their possible contributions to DA disease states and suggest specific phosphorylation sites as targets for therapeutic manipulation of reuptake.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Natural scrapie transmission from infected ewes to their lambs is thought to occur by the oral route around the time of birth. However the hypothesis that scrapie transmission can also occur before ...birth (in utero) is not currently favoured by most researchers. As scrapie is an opportunistic infection with multiple infection routes likely to be functional in sheep, definitive evidence for or against transmission from ewe to her developing fetus has been difficult to achieve. In addition the very early literature on maternal transmission of scrapie in sheep was compromised by lack of knowledge of the role of the PRNP (prion protein) gene in control of susceptibility to scrapie. In this study we experimentally infected pregnant ewes of known PRNP genotype with a distinctive scrapie strain (SSBP/1) and looked for evidence of transmission of SSBP/1 to the offspring. The sheep were from the NPU Cheviot flock, which has endemic natural scrapie from which SSBP/1 can be differentiated on the basis of histology, genetics of disease incidence and strain typing bioassay in mice. We used embryo transfer techniques to allow sheep fetuses of scrapie-susceptible PRNP genotypes to develop in a range of scrapie-resistant and susceptible recipient mothers and challenged the recipients with SSBP/1. Scrapie clinical disease, caused by both natural scrapie and SSBP/1, occurred in the progeny but evidence (including mouse strain typing) of SSBP/1 infection was found only in lambs born to fully susceptible recipient mothers. Progeny were not protected from transmission of natural scrapie or SSBP/1 by washing of embryos to International Embryo Transfer Society standards or by caesarean derivation and complete separation from their birth mothers. Our results strongly suggest that pre-natal (in utero) transmission of scrapie may have occurred in these sheep.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
HIV Vaccine Mystery and Viral Shell Disorder Goh, Gerard Kian-Meng; Dunker, A Keith; Foster, James A ...
Biomolecules (Basel, Switzerland),
05/2019, Volume:
9, Issue:
5
Journal Article
Peer reviewed
Open access
Hundreds of billions of dollars have been spent for over three decades in the search for an effective human immunodeficiency virus (HIV) vaccine with no success. There are also at least two other ...sexually transmitted viruses, for which no vaccine is available, the herpes simplex virus (HSV) and the hepatitis C virus (HCV). Traditional textbook explanatory paradigm of rapid mutation of retroviruses cannot adequately address the unavailability of vaccine for many sexually transmissible viruses, since HSV and HCV are DNA and non-retroviral RNA viruses, respectively, whereas effective vaccine for the horsefly-transmitted retroviral cousin of HIV, equine infectious anemia virus (EIAV), was found in 1973. We reported earlier the highly disordered nature of proteins in outer shells of the HIV, HCV, and HSV. Such levels of disorder are completely absent among the classical viruses, such as smallpox, rabies, yellow fever, and polio viruses, for which efficient vaccines were discovered. This review analyzes the physiology and shell disorder of the various related and non-related viruses to argue that EIAV and the classical viruses need harder shells to survive during harsher conditions of non-sexual transmissions, thus making them vulnerable to antibody detection and neutralization. In contrast, the outer shell of the HIV-1 (with its preferential sexual transmission) is highly disordered, thereby allowing large scale motions of its surface glycoproteins and making it difficult for antibodies to bind to them. The theoretical underpinning of this concept is retrospectively traced to a classical 1920s experiment by the legendary scientist, Oswald Avery. This concept of viral shapeshifting has implications for improved treatment of cancer and infections via immune evasion.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Light chain (AL) amyloidosis is the most common form of systemic amyloid disease, and cardiomyopathy is a dire consequence, resulting in an extremely poor prognosis. AL is characterized by the ...production of monoclonal free light chains that deposit as amyloid fibrils principally in the heart, liver, and kidneys causing organ dysfunction. We have studied the effects of amyloid fibrils, produced from recombinant λ6 light chain variable domains, on metabolic activity of human cardiomyocytes. The data indicate that fibrils at 0.1 μM, but not monomer, significantly decrease the enzymatic activity of cellular NAD(P)H-dependent oxidoreductase, without causing significant cell death. The presence of amyloid fibrils did not affect ATP levels; however, oxygen consumption was increased and reactive oxygen species were detected. Confocal fluorescence microscopy showed that fibrils bound to and remained at the cell surface with little fibril internalization. These data indicate that AL amyloid fibrils severely impair cardiomyocyte metabolism in a dose dependent manner. These data suggest that effective therapeutic intervention for these patients should include methods for removing potentially toxic amyloid fibrils.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Increasing global light pollution1,2 threatens the night-time darkness to which most animals are adapted. Light pollution can have detrimental effects on behavior,3–5 including by disrupting the ...journeys of migratory birds,5,6 sand hoppers,7–9 and moths.10 This is particularly concerning, since many night-active species rely on compass information in the sky, including the moon,11,12 the skylight polarization pattern,13,14 and the stars,15 to hold their course. Even animals not directly exposed to streetlights and illuminated buildings may still experience indirect light pollution in the form of skyglow,3,4 which can extend far beyond urban areas.1,2 While some recent research used simulated light pollution to estimate how skyglow may affect orientation behavior,7–9 the consequences of authentic light pollution for celestial orientation have so far been neglected. Here, we present the results of behavioral experiments at light-polluted and dark-sky sites paired with photographic measurements of each environment. We find that light pollution obscures natural celestial cues and induces dramatic changes in dung beetle orientation behavior, forcing them to rely on bright earthbound beacons in place of their celestial compass. This change in behavior results in attraction toward artificial lights, thereby increasing inter-individual competition and reducing dispersal efficiency. For the many other species of insect, bird, and mammal that rely on the night sky for orientation and migration, these effects could dramatically hinder their vital night-time journeys.
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•Visual compass cues are obscured by skyglow in light-polluted skies•Starlight at a light-polluted site is insufficient for dung beetle orientation•Light pollution led dung beetles to adopt a beaconing strategy
Light pollution illuminating the night sky can obscure the visual compass cues on which many animals rely. In simultaneous experiments at light-polluted and dark-sky sites, Foster et al. show that light pollution forces nocturnal dung beetles to abandon celestial cues, instead moving toward earthbound lights.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
How animals follow the stars Foster, James J.; Smolka, Jochen; Nilsson, Dan-Eric ...
Proceedings of the Royal Society. B, Biological sciences,
01/2018, Volume:
285, Issue:
1871
Journal Article
Peer reviewed
Open access
Throughout history, the stars have provided humans with ever more information about our world, enabling increasingly accurate systems of navigation in addition to fuelling some of the greatest ...scientific controversies. What information animals have evolved to extract from a starry sky and how they do so, is a topic of study that combines the practical and theoretical challenges faced by both astronomers and field biologists. While a number of animal species have been demonstrated to use the stars as a source of directional information, the strategies that these animals use to convert this complex and variable pattern of dim-light points into a reliable ‘stellar orientation’ cue have been more difficult to ascertain. In this review, we assess the stars as a visual stimulus that conveys directional information, and compare the bodies of evidence available for the different stellar orientation strategies proposed to date. In this context, we also introduce new technologies that may aid in the study of stellar orientation, and suggest how field experiments may be used to characterize the mechanisms underlying stellar orientation.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
It is well accepted that a country's GDP may not fully reflect its level of well‐being. In recent years, happiness has emerged as an alternative indicator of well‐being, and research has mainly ...focused on determining the level of happiness. While it is important to look at the level, the distribution of happiness is also a salient aspect in any evaluation of inequality. There has been a growing interest in the distribution of happiness, although the ordinal nature of the data makes the use of standard inequality measures problematic. Our paper contributes to the literature by exploring the distributions for the U.S. from 1972 to 2010. Based on new methods developed for ordinal data, we are able to overcome the problems associated with ordinality and obtain unambiguous rankings of happiness distributions. We also compute the level of happiness inequality using existing measures based on median centred approaches. Further, we decompose the median based inequality measures of happiness by gender, race, and region.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This study aimed to evaluate the efficacy of in situ adeno-associated virus (AAV)-mediated gene delivery into the human corneal limbal region via targeted sub-limbal injection technique. Human ...cadaveric corneal tissues were fixed on an artificial anterior chamber. Feasibility of sub-limbal injection technique was tested using trypan blue and black India ink. An enhanced green fluorescent protein (eGFP) encoding AAV DJ was injected into sub-limbal region. After AAV injection, corneal tissues were incubated in air-lift culture and prepared for immunohistochemical analysis. Cell survivial and expression of eGFP, stem cell markers (p63α and cytokeratin 19 (KRT19)), and differentiation marker cytokeratin 3 (KRT3) were evaluated using confocal microscopy. Both trypan blue and black India ink stained and were retained sub-limbally establishing specificity of the injection technique. Immunohistochemical analysis of corneas injected with AAV DJ-eGFP indicated that AAV-transduced cells in the limbal region co-express eGFP, p63α, and KRT19 and that these transduced cells were capable of differentiating to KRT3 postitive corneal epithelial cells. Our sub-limbal injection technique can target cells in the human limbus in a reproducible and efficient manner. Thus, we demonstrate that in situ injection of corneal limbus may provide a feasible mode of genetic therapy for corneal disorders with an epithelial etiology.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The coronavirus (CoV) family consists of viruses that infects a variety of animals including humans with various levels of respiratory and fecal-oral transmission levels depending on the behavior of ...the viruses' natural hosts and optimal viral fitness. A model to classify and predict the levels of respective respiratory and fecal-oral transmission potentials of the various viruses was built before the outbreak of MERS-CoV using AI and empirically-based molecular tools to predict the disorder level of proteins. Using the percentages of intrinsic disorder (PID) of the nucleocapsid (N) and membrane (M) proteins of CoV, the model easily clustered the viruses into three groups with the SARS-CoV (M PID = 8%, N PID = 50%) falling into Category B, in which viruses have intermediate levels of both respiratory and fecal-oral transmission potentials. Later, MERS-CoV (M PID = 9%, N PID = 44%) was found to be in Category C, which consists of viruses with lower respiratory transmission potential but with higher fecal-oral transmission capabilities. Based on the peculiarities of disorder distribution, the SARS-CoV-2 (M PID = 6%, N PID = 48%) has to be placed in Category B. Our data show however, that the SARS-CoV-2 is very strange with one of the hardest protective outer shell, (M PID = 6%) among coronaviruses. This means that it might be expected to be highly resilient in saliva or other body fluids and outside the body. An infected body is likelier to shed greater numbers of viral particles since the latter is more resistant to antimicrobial enzymes in body fluids. These particles are also likelier to remain active longer. These factors could account for the greater contagiousness of the SARS-CoV-2 and have implications for efforts to prevent its spread.
•AI molecular tools cluster percentages of intrinsic disorder (PID) of the nucleocapsid (N) and membrane (M) proteins.•SARS-CoV-2 has intermediate levels of respiratory and fecal-oral transmission potentials.•SARS-CoV-2 is very strange with one of the hardest protective outer shell, (M PID=6%) among coronaviruses.•Because of its harder outer shell, SARS-CoV-2 is likely to be more resistant to antimicrobial enzymes in body fluids.•As a result, an infected body is likelier to shed greater numbers of viral particles that remain active longer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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