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PloS One 2018Current anti-cancer strategy takes advantage of tumour specific abnormalities in DNA damage response to radio- or chemo-therapy. Inhibition of the ATR/Chk1 pathway has...
Current anti-cancer strategy takes advantage of tumour specific abnormalities in DNA damage response to radio- or chemo-therapy. Inhibition of the ATR/Chk1 pathway has been shown to be synthetically lethal in cells with high levels of oncogene-induced replication stress and in p53- or ATM- deficient cells. In the presented study, we aimed to elucidate molecular mechanisms underlying radiosensitization of T-lymphocyte leukemic MOLT-4 cells by VE-821, a higly potent and specific inhibitor of ATR. We combined multiple approaches: cell biology techniques to reveal the inhibitor-induced phenotypes, and quantitative proteomics, phosphoproteomics, and metabolomics to comprehensively describe drug-induced changes in irradiated cells. VE-821 radiosensitized MOLT-4 cells, and furthermore 10 μM VE-821 significantly affected proliferation of sham-irradiated MOLT-4 cells. We detected 623 differentially regulated phosphorylation sites. We revealed changes not only in DDR-related pathways and kinases, but also in pathways and kinases involved in maintaining cellular metabolism. Notably, we found downregulation of mTOR, the main regulator of cellular metabolism, which was most likely caused by an off-target effect of the inhibitor, and we propose that mTOR inhibition could be one of the factors contributing to the phenotype observed after treating MOLT-4 cells with 10 μM VE-821. In the metabolomic analysis, 206 intermediary metabolites were detected. The data indicated that VE-821 potentiated metabolic disruption induced by irradiation and affected the response to irradiation-induced oxidative stress. Upon irradiation, recovery of damaged deoxynucleotides might be affected by VE-821, hampering DNA repair by their deficiency. Taken together, this is the first study describing a complex scenario of cellular events that might be ATR-dependent or triggered by ATR inhibition in irradiated MOLT-4 cells. Data are available via ProteomeXchange with identifier PXD008925.
Topics: Amino Acid Motifs; Ataxia Telangiectasia Mutated Proteins; Binding Sites; Biomarkers; Cell Cycle Checkpoints; Cell Line, Tumor; Computational Biology; Gamma Rays; Gene Ontology; Humans; Metabolome; Metabolomics; Phosphoproteins; Phosphorylation; Protein Binding; Protein Kinase Inhibitors; Proteome; Proteomics; Pyrazines; Radiation Tolerance; Radiation-Sensitizing Agents; Signal Transduction; Sulfones; TOR Serine-Threonine Kinases
PubMed: 30001349
DOI: 10.1371/journal.pone.0199349 -
Biology Letters Nov 2022Species that seasonally moult from brown to white to match snowy backgrounds become conspicuous and experience increased predation risk as snow cover duration declines....
Species that seasonally moult from brown to white to match snowy backgrounds become conspicuous and experience increased predation risk as snow cover duration declines. Long-term adaptation to camouflage mismatch in a changing climate might occur through phenotypic plasticity in colour moult phenology and or evolutionary shifts in moult rate or timing. Also, adaptation may include evolutionary shifts towards winter brown phenotypes that forgo the winter white moult. Most studies of these processes have occurred in winter white populations, with little attention to polymorphic populations with sympatric winter brown and winter white morphs. Here, we used remote camera traps to record moult phenology and mismatch in two polymorphic populations of Arctic foxes in Sweden over 2 years. We found that the colder, more northern population moulted earlier in the autumn and later in the spring. Next, foxes moulted earlier in the autumn and later in the spring during colder and snowier years. Finally, white foxes experienced relatively low camouflage mismatch while blue foxes were mismatched against snowy backgrounds most of the autumn through the spring. Because the brown-on-white mismatch imposes no evident costs, we predict that as snow duration decreases, increasing blue morph frequencies might help facilitate species persistence.
Topics: Animals; Foxes; Climate Change; Color; Molting; Snow; Seasons; Arctic Regions
PubMed: 36382371
DOI: 10.1098/rsbl.2022.0334 -
The ISME Journal Dec 2022In invertebrates, the cuticle is the first and major protective barrier against predators and pathogen infections. While immune responses and behavioral defenses are...
In invertebrates, the cuticle is the first and major protective barrier against predators and pathogen infections. While immune responses and behavioral defenses are also known to be important for insect protection, the potential of cuticle-associated microbial symbionts to aid in preventing pathogen entry during molting and throughout larval development remains unexplored. Here, we show that bacterial symbionts of the beetle Lagria villosa inhabit unusual dorsal invaginations of the insect cuticle, which remain open to the outer surface and persist throughout larval development. This specialized location enables the release of several symbiont cells and the associated protective compounds during molting. This facilitates ectosymbiont maintenance and extended defense during larval development against antagonistic fungi. One Burkholderia strain, which produces the antifungal compound lagriamide, dominates the community across all life stages, and removal of the community significantly impairs the survival probability of young larvae when exposed to different pathogenic fungi. We localize both the dominant bacterial strain and lagriamide on the surface of eggs, larvae, pupae, and on the inner surface of the molted cuticle (exuvia), supporting extended protection. These results highlight adaptations for effective defense of immature insects by cuticle-associated ectosymbionts, a potentially key advantage for a ground-dwelling insect when confronting pathogenic microbes.
Topics: Animals; Coleoptera; Molting; Burkholderia; Pupa; Larva; Insecta; Fungi
PubMed: 36056153
DOI: 10.1038/s41396-022-01311-x -
Scientific Reports Aug 2021Recently, we reported a novel mode of action in monarch butterfly (Danaus plexippus) larvae exposed to neonicotinoid insecticides: arrest in pupal ecdysis following...
Recently, we reported a novel mode of action in monarch butterfly (Danaus plexippus) larvae exposed to neonicotinoid insecticides: arrest in pupal ecdysis following successful larval ecdysis. In this paper, we explore arrested pupal ecdysis in greater detail and propose adverse outcome pathways to explain how neonicotinoids cause this effect. Using imidacloprid as a model compound, we determined that final-instar monarchs, corn earworms (Helicoverpa zea), and wax moths (Galleria mellonella) showed high susceptibility to arrested pupal ecdysis while painted ladies (Vanessa cardui) and red admirals (Vanessa atalanta) showed low susceptibility. Fall armyworms (Spodoptera frugiperda) and European corn borers (Ostrinia nubilalis) were recalcitrant. All larvae with arrested ecdysis developed pupal cuticle, but with incomplete shedding of larval cuticle and unexpanded pupal appendages; corn earworm larvae successfully developed into adults with unexpanded appendages. Delayed initiation of pupal ecdysis was also observed with treated larvae. Imidacloprid exposure was required at least 26 h prior to pupal ecdysis to disrupt the molt. These observations suggest neonicotinoids may disrupt the function of crustacean cardioactive peptide (CCAP) neurons, either by directly acting on their nicotinic acetylcholine receptors or by acting on receptors of inhibitory neurons that regulate CCAP activity.
Topics: Animals; Insecticides; Larva; Molting; Neonicotinoids; Neurons; Neuropeptides; Nitro Compounds; Pupa; Receptors, Nicotinic
PubMed: 34349192
DOI: 10.1038/s41598-021-95284-0 -
Ecology and Evolution Jan 2018Sexual selection and social selection are two important theories proposed for explaining the evolution of colorful ornamental traits in animals. Understanding signal...
Sexual selection and social selection are two important theories proposed for explaining the evolution of colorful ornamental traits in animals. Understanding signal honesty requires studying how environmental and physiological factors during development influence the showy nature of sexual and social ornaments. We experimentally manipulated physiological stress and immunity status during the molt in adult king penguins (), and studied the consequences of our treatments on colourful ornaments (yellow-orange and UV beak spots and yellow-orange auricular feather patches) known to be used in sexual and social contexts in this species. Whereas some ornamental features showed strong condition-dependence (yellow auricular feather chroma, yellow and UV chroma of the beak), others were condition-independent and remained highly correlated before and after the molt (auricular patch size and beak UV hue). Our study provides a rare examination of the links between ornament determinism and selection processes in the wild. We highlight the coexistence of ornaments costly to produce that may be honest signals used in mate choice, and ornaments for which honesty may be enforced by social mediation or rely on genetic constraints.
PubMed: 29375781
DOI: 10.1002/ece3.3677 -
PloS One 2017Molt-4 leukemia cells undergo p53-dependent apoptosis accompanied by accumulation of de novo ceramide after 14 hours of γ-irradiation. In order to identify the...
Molt-4 leukemia cells undergo p53-dependent apoptosis accompanied by accumulation of de novo ceramide after 14 hours of γ-irradiation. In order to identify the potential mediators involved in ceramide accumulation and the cell death response, differentially expressed genes were identified by Affymetrix Microarray Analysis. Molt-4-LXSN cells, expressing wild type p53, and p53-deficient Molt-4-E6 cells were irradiated and harvested at 3 and 8 hours post-irradiation. Human genome U133 plus 2.0 array containing >47,000 transcripts was used for gene expression profiling. From over 10,000 probes, 281 and 12 probes were differentially expressed in Molt-4-LXSN and Molt-4-E6 cells, respectively. Data analysis revealed 63 (upregulated) and 20 (downregulated) genes (>2 fold) in Molt-4-LXSN at 3 hours and 140 (upregulated) and 21 (downregulated) at 8 hours post-irradiation. In Molt-4-E6 cells, 5 (upregulated) genes each were found at 3 hours and 8 hours, respectively. In Molt-4-LXSN cells, a significant fraction of the genes with altered expression at 3 hours were found to be involved in apoptosis signaling pathway (BCL2L11), p53 pathway (PMAIP1, CDKN1A and FAS) and oxidative stress response (FDXR, CROT and JUN). Similarly, at 8 hours the genes with altered expression were involved in the apoptosis signaling pathway (BAX, BIK and JUN), p53 pathway (BAX, CDKN1A and FAS), oxidative stress response (FDXR and CROT) and p53 pathway feedback loops 2 (MDM2 and CDKN1A). A global molecular and biological interaction map analysis showed an association of these altered genes with apoptosis, senescence, DNA damage, oxidative stress, cell cycle arrest and caspase activation. In a targeted study, activation of apoptosis correlated with changes in gene expression of some of the above genes and revealed sequential activation of both intrinsic and extrinsic apoptotic pathways that precede ceramide accumulation and subsequent execution of apoptosis. One or more of these altered genes may be involved in p53-dependent ceramide accumulation.
Topics: Apoptosis; Cell Line, Tumor; Gamma Rays; Humans; Leukemia; Multigene Family; Systems Biology; Tumor Suppressor Protein p53
PubMed: 29272311
DOI: 10.1371/journal.pone.0190221 -
Current Biology : CB Jul 2021Many aspects of bird migration are necessarily innate. However, the extent of deterministic genetic control, environmental influence, and individual decision making in...
Many aspects of bird migration are necessarily innate. However, the extent of deterministic genetic control, environmental influence, and individual decision making in the control of migration remains unclear. Globally, few cases of rapid and dramatic life-history changes resulting in novel migration strategies are known. An example is latitudinal trans-hemispheric breeding colonization, whereby a subpopulation suddenly begins breeding on its non-breeding range. These life-history reversals demand concomitant changes in the timing of migration, feather molt, and breeding if the population is to remain viable. Cliff swallows, Petrochelidon pyrrhonota, are long-distance migrants that breed in North America and spend the non-breeding season mostly in South America. However, in 2015, a small population switched hemispheres by breeding successfully in Argentina, over 8,000 km from the nearest potential source, after presumably failed attempts. This provided a unique chance to characterize the early mechanisms of change in migratory behavior and phenology and to assess the possibility of double breeding. We tracked cliff swallows with geolocators following their second and fourth breeding seasons in Argentina, documenting inverted seasonality, three new migratory patterns and non-breeding areas (North America, Mesoamerica, and South America), and a shift of molt phenology by approximately 6 months, all possibly arising within a single generation. These birds did not practice migratory double breeding, although some spent the boreal summer in the traditional breeding range. Our data show that fundamental phenological changes occurred very rapidly during colonization and that phenotypic plasticity can underlie profound changes in the life histories of migratory birds.
Topics: Animal Migration; Animals; Central America; Feathers; Female; Male; Molting; North America; Seasons; South America; Swallows
PubMed: 33951458
DOI: 10.1016/j.cub.2021.04.019 -
Poultry Science Nov 2016The aim of this study was to investigate the efficacy of feed-grade preparations of mannan oligosaccharides ( MOS: ) and oregano essential oil ( OEO: ) in forced molted... (Comparative Study)
Comparative Study
Comparative evaluation of dietary supplementation with mannan oligosaccharide and oregano essential oil in forced molted and fully fed laying hens between 82 and 106 weeks of age.
The aim of this study was to investigate the efficacy of feed-grade preparations of mannan oligosaccharides ( MOS: ) and oregano essential oil ( OEO: ) in forced molted or fully fed 82-week-old, laying hens. A 2 × 3 factorial experiment investigated the influence of molting vs. full feeding and dietary supplements [i.e., unsupplemented control, MOS (1 g/kg) diet, and OEO (24 mg/kg) diet] on production parameters, egg quality, serum stress indicators, blood constituents, tibial characteristics, liver antioxidant status, and cecal microflora composition. A total of 864 Single Comb White Leghorn hens were randomly assigned to 6 treatments, each with 6 replicates of 24 hens each, and studied for 25 wk. Hens were fed a molt diet containing of 50% alfalfa and 50% wheat bran ( AA+WB: ) for 12 d, then returned to the laying ration. Results indicate that molt vs. full feed impacted more on most variables measured than supplementation or supplement type. Significant (P < 0.01) interactions between molting and diet were observed for the egg production, egg weight, egg mass, and feed conversion ratio ( FCR: ). In fully fed hens, MOS supplementation improved (P < 0.01) the egg production, egg weight, and FCR, and an OEO addition significantly improved the egg production and FCR in forced molted hens. Molting improved egg quality despite the significant regression in ovary and oviduct weight (P < 0.01), though supplements showed no influence. The bone ash (P < 0.01) and mineral content (P < 0.05) of molted hens were significantly lower than those of fully fed counterparts; however, poor mineralization was not reflected in the bones' mechanical properties. No significant differences were observed among treatments for hematological characteristics. Both the MOS and particularly the OEO supplementation improved (P < 0.01) liver antioxidant status and mitigated the significant increase in cecal pathogenic bacteria after molt. Our results indicate that full feeding with an aa+wb diet is an effective non-feed-removal method for molted hens, the benefit of which can be improved with MOS and OEO supplementation.
Topics: Animal Feed; Animals; Chickens; Diet; Female; Mannans; Molting; Oils, Volatile; Oligosaccharides; Origanum; Prebiotics; Random Allocation
PubMed: 27143766
DOI: 10.3382/ps/pew140 -
Ecology and Evolution Jan 2021Molt strategies have received relatively little attention in current ornithology, and knowledge concerning the evolution, variability and extent of molt is sparse in...
Molt strategies have received relatively little attention in current ornithology, and knowledge concerning the evolution, variability and extent of molt is sparse in many bird species. This is especially true for East Asian species where assumptions on molt patterns are based on incomplete information. We provide evidence indicating a complex postbreeding molt strategy and variable molt extent among the Pallas's Grasshopper Warbler , based on data from six ringing sites situated along its flyway from the breeding grounds to the wintering areas. Detailed study revealed for the first time that in most individuals wing feather molt proceeds from the center both toward the body and the wing-tip, a molt pattern known as divergent molt (which is rare among Palearctic passerines). In the Russian Far East, where both breeding birds and passage migrants occur, a third of the adult birds were molting in late summer. In Central Siberia, at the northwestern limit of its distribution, adult individuals commenced their primary molt partly divergently and partly with unknown sequence. During migration in Mongolia, only descendantly (i.e., from the body toward the wing-tip) molting birds were observed, while further south in Korea, Hong Kong, and Thailand the proportion of potential eccentric and divergent feather renewal was not identifiable since the renewed feathers were already fully grown as expected. We found an increase in the mean number of molted primaries during the progress of the autumn migration. Moderate body mass levels and low-fat and muscle scores were observed in molting adult birds, without any remarkable increase in the later season. According to optimality models, we suggest that an extremely short season of high food abundance in tall grass habitats and a largely overland route allow autumn migration with low fuel loads combined with molt migration in at least a part of the population. This study highlights the importance of further studying molt strategy as well as stopover behavior decisions and the trade-offs among migratory birds that are now facing a panoply of anthropogenic threats along their flyways.
PubMed: 33437411
DOI: 10.1002/ece3.7098 -
Microorganisms Dec 2017Subsocial wood feeding cockroaches in the genus , the sister group of termites, retain their symbiotic gut flagellates during the host molting cycle, but in lower... (Review)
Review
Subsocial wood feeding cockroaches in the genus , the sister group of termites, retain their symbiotic gut flagellates during the host molting cycle, but in lower termites, closely related flagellates die prior to host ecdysis. Although the prevalent view is that termite flagellates die because of conditions of starvation and desiccation in the gut during the host molting cycle, the work of L.R. Cleveland in the 1930s through the 1960s provides a strong alternate hypothesis: it was the changed hormonal environment associated with the origin of eusociality and its concomitant shift in termite developmental ontogeny that instigates the death of the flagellates in termites. Although the research on termite gut microbial communities has exploded since the advent of modern molecular techniques, the role of the host hormonal environment on the life cycle of its gut flagellates has been neglected. Here Cleveland's studies are revisited to provide a basis for re-examination of the problem, and the results framed in the context of two alternate hypotheses: the flagellate symbionts are victims of the change in host social status, or the flagellates have become incorporated into the life cycle of the eusocial termite colony. Recent work on parasitic protists suggests clear paths for exploring these hypotheses and for resolving long standing issues regarding sexual-encystment cycles in flagellates of the -termite lineage using molecular methodologies, bringing the problem into the modern era.
PubMed: 29258251
DOI: 10.3390/microorganisms5040082