bluuebunny/crossref_metadata_2025_split huggingface dataset:
Divergence in DNA photorepair efficiency among genotypes from contrasting UV radiation environments in nature
Authors: Miner Brooks E. , Kulling Paige M. , Beer Karlyn D. , Kerr Benjamin 
Published: November 2015

AbstractPopulations of organisms routinely face abiotic selection pressures, and a central goal of evolutionary biology is to understand the mechanistic underpinnings of adaptive phenotypes. Ultraviolet radiation (UVR) is one of earth's most pervasive environmental stressors, potentially damaging DNA in any organism exposed to solar radiation. We explored mechanisms underlying differential survival following UVR exposure in genotypes of the water flea Daphnia melanica derived from natural ponds of differing UVR intensity. The UVR tolerance of a D. melanica genotype from a high‐UVR habitat depended on the presence of visible and UV‐A light wavelengths necessary for photoenzymatic repair of DNA damage, a repair pathway widely shared across the tree of life. We then measured the acquisition and repair of cyclobutane pyrimidine dimers, the primary form of UVR‐caused DNA damage, in D. melanica DNA following experimental UVR exposure. We demonstrate that genotypes from high‐UVR habitats repair DNA damage faster than genotypes from low‐UVR habitats in the presence of visible and UV‐A radiation necessary for photoenzymatic repair, but not in dark treatments. Because differences in repair rate only occurred in the presence of visible and UV‐A radiation, we conclude that differing rates of DNA repair, and therefore differential UVR tolerance, are a consequence of variation in photoenzymatic repair efficiency. We then rule out a simple gene expression hypothesis for the molecular basis of differing repair efficiency, as expression of the CPD photolyase gene photorepair did not differ among D. melanica lineages, in both the presence and absence of UVR.
Eco‐morphological differentiation in Lake Magadi tilapia, an extremophile cichlid fish living in hot, alkaline and hypersaline lakes in East Africa
Authors: Kavembe Geraldine D. , Kautt Andreas F. , Machado‐Schiaffino Gonzalo , Meyer Axel 
Published: November 2015

AbstractEcological diversification through divergent selection is thought to be a major force during the process of adaptive radiations. However, the large sizes and complexity of most radiations such as those of the cichlids in the African Great Lakes make it impossible to infer the exact evolutionary history of any population divergence event. The genusAlcolapia,a small cichlid lineage endemic to Lakes Magadi and Natron in East Africa, exhibits phenotypes similar to some of those found in cichlids of the radiations of the African Great Lakes. The simplicity withinAlcolapiamakes it an excellent model system to investigate ecological diversification and speciation. We used an integrated approach including population genomics based onRAD‐seq data, geometric morphometrics and stable isotope analyses to investigate the eco‐morphological diversification of tilapia in Lake Magadi and its satellite lake Little Magadi. Additionally, we reconstructed the demographic history of the species using coalescent simulations based on the joint site frequency spectrum. The population in Little Magadi has a characteristically upturned mouth—possibly an adaptation to feeding on prey from the water surface. Eco‐morphological differences between populations within Lake Magadi are more subtle, but are consistent with known ecological differences between its lagoons such as high concentrations of nitrogen attributable to extensive guano deposits in Rest of Magadi relative to Fish Springs Lagoon. All populations diverged simultaneously only about 1100 generations ago. Differences in levels of gene flow between populations and the effective population sizes have likely resulted in the inferred heterogeneous patterns of genome‐wide differentiation.
RAD sequencing reveals within‐generation polygenic selection in response to anthropogenic organic and metal contamination in North Atlantic Eels
Authors: Laporte M. , Pavey S. A. , Rougeux C. , Pierron F. , Lauzent M. , Budzinski H. , Labadie P. , Geneste E. , Couture P. , Baudrimont M. , Bernatchez L. 
Published: November 2015

AbstractMeasuring the effects of selection on the genome imposed by human‐altered environment is currently a major goal in ecological genomics. Given the polygenic basis of most phenotypic traits, quantitative genetic theory predicts that selection is expected to cause subtle allelic changes among covarying loci rather than pronounced changes at few loci of large effects. The goal of this study was to test for the occurrence of polygenic selection in both North Atlantic eels (European Eel, Anguilla anguilla and American Eel, A. rostrata), using a method that searches for covariation among loci that would discriminate eels from ‘control’ vs. ‘polluted’ environments and be associated with specific contaminants acting as putative selective agents. RAD‐seq libraries resulted in 23 659 and 14 755 filtered loci for the European and American Eels, respectively. A total of 142 and 141 covarying markers discriminating European and American Eels from ‘control’ vs. ‘polluted’ sampling localities were obtained using the Random Forest algorithm. Distance‐based redundancy analyses (db‐RDAs) were used to assess the relationships between these covarying markers and concentration of 34 contaminants measured for each individual eel. PCB153, 4′4′DDE and selenium were associated with covarying markers for both species, thus pointing to these contaminants as major selective agents in contaminated sites. Gene enrichment analyses suggested that sterol regulation plays an important role in the differential survival of eels in ‘polluted’ environment. This study illustrates the power of combining methods for detecting signals of polygenic selection and for associating variation of markers with putative selective agents in studies aiming at documenting the dynamics of selection at the genomic level and particularly so in human‐altered environments.
Targeted capture and resequencing of 1040 genes reveal environmentally driven functional variation in grey wolves
Authors: Schweizer Rena M. , Robinson Jacqueline , Harrigan Ryan , Silva Pedro , Galverni Marco , Musiani Marco , Green Richard E. , Novembre John , Wayne Robert K. 
Published: November 2015

AbstractIn an era of ever‐increasing amounts of whole‐genome sequence data for individuals and populations, the utility of traditional single nucleotide polymorphisms (SNPs) array‐based genome scans is uncertain. We previously performed a SNP array‐based genome scan to identify candidate genes under selection in six distinct grey wolf (Canis lupus) ecotypes. Using this information, we designed a targeted capture array for 1040 genes, including all exons and flanking regions, as well as 5000 1‐kb nongenic neutral regions, and resequenced these regions in 107 wolves. Selection tests revealed striking patterns of variation within candidate genes relative to noncandidate regions and identified potentially functional variants related to local adaptation. We found 27% and 47% of candidate genes from the previous SNP array study had functional changes that were outliers in sweed and bayenv analyses, respectively. This result verifies the use of genomewide SNP surveys to tag genes that contain functional variants between populations. We highlight nonsynonymous variants in APOB, LIPG and USH2A that occur in functional domains of these proteins, and that demonstrate high correlation with precipitation seasonality and vegetation. We find Arctic and High Arctic wolf ecotypes have higher numbers of genes under selection, which highlight their conservation value and heightened threat due to climate change. This study demonstrates that combining genomewide genotyping arrays with large‐scale resequencing and environmental data provides a powerful approach to discern candidate functional variants in natural populations.
Protein aggregation as an antibiotic design strategy
Authors: Bednarska Natalia G. , van Eldere Johan , Gallardo Rodrigo , Ganesan Ashok , Ramakers Meine , Vogel Isabel , Baatsen Pieter , Staes An , Goethals Marc , Hammarström Per , Nilsson K. Peter R. , Gevaert Kris , Schymkowitz Joost , Rousseau Frederic 
Published: November 2015

SummaryTaking advantage of the xenobiotic nature of bacterial infections, we tested whether the cytotoxicity of protein aggregation can be targeted to bacterial pathogens without affecting their mammalian hosts. In particular, we examined if peptides encoding aggregation‐prone sequence segments of bacterial proteins can display antimicrobial activity by initiating toxic protein aggregation in bacteria, but not in mammalian cells. Unbiased in vitro screening of aggregating peptide sequences from bacterial genomes lead to the identification of several peptides that are strongly bactericidal against methicillin‐resistant Staphylococcus aureus. Upon parenteral administration in vivo, the peptides cured mice from bacterial sepsis without apparent toxic side effects as judged from histological and hematological evaluation. We found that the peptides enter and accumulate in the bacterial cytosol where they cause aggregation of bacterial polypeptides. Although the precise chain of events that leads to cell death remains to be elucidated, the ability to tap into aggregation‐prone sequences of bacterial proteomes to elicit antimicrobial activity represents a rich and unexplored chemical space to be mined in search of novel therapeutic strategies to fight infectious diseases.
Glucagon‐like peptide 2 counteracts the mucosal damage and the neuropathy induced by chronic treatment with cisplatin in the mouse gastric fundus
Authors: Pini A. , Garella R. , Idrizaj E. , Calosi L. , Baccari M. C. , Vannucchi M. G. 
Published: November 2015

AbstractBackgroundGlucagon‐like peptide‐2 (GLP‐2) is a pleiotropic hormone synthesized and secreted by the enteroendocrine ‘L’ cells able to exert intestine‐trophic and anti‐inflammatory effects. The antineoplastic drug cisplatin causes gastrointestinal alterations with clinical symptoms (nausea and vomiting) that greatly affect the therapy compliance. Experimentally, it has been reported that chronic cisplatin treatment caused mucosal damage and enteric neuropathy in the rat colon.MethodsWe investigated, through a combined immunohistochemical and functional approach, whether [Gly2]GLP‐2, a GLP‐2 analog, was able to counteract the detrimental effects of long‐term cisplatin administration in the mucosa and myenteric neurons of mouse gastric fundus.Key ResultsMorphological experiments showed a reduction in the epithelium thickness in cisplatin‐treated mice, which was prevented by [Gly2]GLP‐2 co‐treatment. Immunohistochemistry demonstrated that cisplatin caused a significant decrease in myenteric neurons, mainly those expressing neuronal nitric oxide synthase (nNOS), that was prevented by [Gly2]GLP‐2 co‐treatment. In the functional experiments, [Gly2]GLP‐2 co‐treatment counteracted the increase in amplitude of the neurally induced contractions observed in strips from cisplatin‐treated animals. The NO synthesis inhibitor L‐NG‐nitro arginine caused an increase in amplitude of the contractile responses that was greater in preparations from cisplatin+[Gly2]GLP‐2 treated mice compared to the cisplatin‐treated ones.Conclusions & InferencesThe results demonstrate that in cisplatin long‐term treated mice [Gly2]GLP‐2 is able to counteract both the mucosal gastric fundus damage, by preventing the epithelium thickness decrease, and the neuropathy, by protecting the nNOS neurons. Taken together, the present data suggest that [Gly2]GLP‐2 could represent an effective strategy to overcome the distressing gastrointestinal symptoms present during the anti‐neoplastic therapy.
Maximum upper esophageal sphincter (UES) admittance: a non‐specific marker of UES dysfunction
Authors: Cock C. , Besanko L. , Kritas S. , Burgstad C. M. , Thompson A. , Heddle R. , Fraser R. J. L. , Omari T. I. 
Published: November 2015

AbstractBackgroundAssessment of upper esophageal sphincter (UES) motility is challenging, as functionally, UES relaxation and opening are distinct. We studied novel parameters, UES admittance (inverse of nadir impedance), and 0.2‐s integrated relaxation pressure (IRP), in patients with cricopharyngeal bar (CPB) and motor neuron disease (MND), as predictors of UES dysfunction.MethodsSixty‐six healthy subjects (n = 50 controls 20–80 years; n = 16 elderly >80 years), 11 patients with CPB (51–83 years) and 16 with MND (58–91 years) were studied using pharyngeal high‐resolution impedance manometry. Subjects received 5 × 5 mL liquid (L) and viscous (V) boluses. Admittance and IRP were compared by age and between groups. A p < 0.05 was considered significant.Key ResultsIn healthy subjects, admittance was reduced (L: p = 0.005 and V: p = 0.04) and the IRP higher with liquids (p = 0.02) in older age. Admittance was reduced in MND compared to both healthy groups (Young: p < 0.0001 for both, Elderly L: p < 0.0001 and V: p = 0.009) and CPB with liquid (p = 0.001). Only liquid showed a higher IRP in MND patients compared to controls (p = 0.03), but was similar to healthy elderly and CPB patients. Only admittance differentiated younger controls from CPB (L: p = 0.0002 and V: p < 0.0001), with no differences in either parameter between CPB and elderly subjects.Conclusions & InferencesThe effects of aging and pathology were better discriminated by UES maximum admittance, demonstrating greater statistical confidence across bolus consistencies as compared to 0.2‐s IRP. Maximum admittance may be a clinically useful determinate of UES dysfunction.
The relationship among gastroparetic symptoms, quality of life, and gastric emptying in patients referred for gastric emptying testing
Authors: DiBaise J. K. , Patel N. , Noelting J. , Dueck A. C. , Roarke M. , Crowell M. D. 
Published: November 2015

AbstractBackgroundSymptoms suggestive of gastroparesis are non‐specific and conflicting reports exist regarding the ability of symptoms to predict the presence of gastroparesis. Our aim, therefore, was to evaluate the relationships between gastroparetic symptoms and their impact on quality of life and determine their relationship with clinical factors and gastric emptying.MethodsGastric emptying scintigraphy, sociodemographic features, health care resource utilization, gastroparetic symptoms, and quality of life using validated questionnaires were obtained from consecutive patients referred for gastric emptying testing (GET). Descriptive analyses were conducted and logistic regression was performed to evaluate associations with abnormal gastric emptying after controlling for other covariates.Key ResultsTwo hundred and sixty‐six patients participated (195 females; mean age, 49.1 ± 17.6 years); 75% met Rome III criteria for functional dyspepsia. Gastric emptying was delayed in 28.2% at 4 h; the delay was mild in 48%, moderate in 20% and severe in 32%. Nausea/emesis and postprandial fullness, but not bloating, were significantly greater in those with delayed emptying. Postprandial fullness was most severe. Weak correlations were identified between symptom severity and the severity of gastric emptying delay. Quality of life was also lower in the delayed emptying group. Logistic regression analysis demonstrated associations between delayed gastric emptying and lower quality of life and increased symptom severity.Conclusions & InferencesIn patients referred for GET, gastroparetic symptoms were more severe in those with delayed emptying. A decrease in quality of life in those with delayed gastric emptying was also present; this was not related to the severity of the delay in gastric emptying.
Highly unsaturated fatty acids in nature: what we know and what we need to learn
Authors: Twining Cornelia W. , Brenna J. Thomas , Hairston Nelson G. , Flecker Alexander S. 
Published: November 2015

The supply and demand of omega‐3 highly unsaturated fatty acids (ω‐3 HUFA) in natural ecosystems may lead to resource limitation in a diverse array of animal taxa. Here, we review why food quality in terms of ω‐3 HUFAs is important, particularly for neural tissue, across a diversity of animal taxa ranging from invertebrate zooplankton to vertebrates (including humans). Our review is focused on ω‐3 HUFAs rather than other unsaturated fatty acids because these compounds are especially important biochemically, but scarce in nature. We discuss the dichotomy between ω‐3 HUFA availability between aquatic primary producers, which are often rich in these compounds, and terrestrial primary producers, which are contain little to none of them. We describe the use of fatty acids as qualitative and quantitative tracers for reconstructing animal diets in natural ecosystems. Next, we discuss both direct and indirect ecological implications of ω‐3 HUFA limitation at the individual, population, food web, and ecosystem scales, which include: changes in behavior, species composition, secondary production rates, trophic transfer efficiency and cross‐ecosystem subsidies. We finish by highlighting future research priorities including a need for more research on ω‐3 HUFAs in terrestrial systems, more research their importance for higher order consumers, and more research on the food web and ecosystem‐scale effects of ω‐3 HUFA limitation.SynthesisMismatches between the supply of and demand for omega‐3 highly unsaturated fatty acids (ω‐3 HUFA) in natural ecosystems have the potential to result in resource limitation across a diverse array of ecosystems. We combined perspectives from ecology and nutritional science to develop a unified synthesis of ω‐3 HUFA ecology. We reviewed the importance of ω‐3 HUFAs for animals, the striking differences in ω‐3 HUFA availability at the base of terrestrial versus aquatic food webs, and the implications of ω‐3 HUFA limitation for food webs. We finished by highlighting research priorities in the field including more research on ω‐3 HUFAs in terrestrial systems, on higher order consumers, and at the food web and ecosystem‐scales.
Pain Self‐Efficacy and Fear of Movement are Similarly Associated with Pain Intensity and Disability in Italian Patients with Chronic Low Back Pain
Authors: Ferrari Silvano , Chiarotto Alessandro , Pellizzer Marta , Vanti Carla , Monticone Marco 
Published: November 2015

AbstractThe purpose of this study was to investigate cross‐sectional associations of pain self‐efficacy and fear of movement with pain intensity and disability in Italian patients with chronic low back pain (CLBP). One hundred and three adult outpatients with nonspecific CLBP were included in the study. Socio‐demographic and clinical characteristics were assessed, together with Italian versions of self‐reported questionnaires to measure the four constructs of interest. Multiple linear regression models were built with psychosocial constructs as main determinants, and pain intensity and disability as outcomes. Potential confounding of socio‐demographic and clinical characteristics was assessed. Pain self‐efficacy and fear of movement displayed moderate correlations with pain intensity (r = −0.41 and 0.42, respectively) and disability (−0.55 and 0.54). Association models adjusted for pain intensity showed that both pain self‐efficacy (β = −0.35, 95% CI = −0.5; −0.2, R2 = 41%) and fear of movement (β = 0.65, 95% CI = 0.36; 0.93, R2 = 40%) are significantly and strongly associated with disability. Pain self‐efficacy was no longer significantly associated with pain intensity when disability was added as a confounder to the model, whereas fear of movement retained its significant association (β = 0.06, 95% CI = 0.00;0.11, R2 = 30%). No other variables acted as confounders in these associations. Pain self‐efficacy and fear of movement are very similarly associated with main outcomes in this sample of Italian patients with CLBP. The results of this study suggest that both psychosocial constructs should be considered in clinical management. Future studies should investigate whether these findings can be replicated in other samples, in longitudinal designs and if other variables not measured in this study confound the associations.
Pathophysiological Mechanisms Involved in Vasomotor Disturbances in Complex Regional Pain Syndrome and Implications for Therapy: A Review
Authors: Kortekaas Minke C. , Niehof Sjoerd P. , Stolker Robert J. , Huygen Frank J.P.M. 
Published: November 2015

AbstractComplex regional pain syndrome (CRPS) is characterized by continuous pain, disproportional to the initial trauma. It usually spreads to the distal parts of the affected limb. Besides continuing pain, a mix of sensory, sudo‐ and vasomotor disturbances, motor dysfunction, and trophic changes is responsible for physical complaints. Vasomotor disturbance is characterized by changes in skin temperature and color. In CRPS patients with a cold extremity, a decrease in blood flow can cause decreased tissue saturation and tissue acidosis, resulting in ischemic pain. The pathophysiology of vasomotor disturbances is not completely understood. Temperature asymmetry is generally assumed as a result of disturbance in the sympathetic nervous system. Vasodilating drugs and sympathetic blockade have been cornerstones of therapy in cold CRPS for years. However, only a limited part of these patients improve on this kind of therapies. Research has shown a pivotal role for inflammation in the pathophysiology of CRPS. Inflammation can result in endothelial dysfunction. Endothelial function plays an important role in the local regulation of vascular tone. Endothelial dysfunction could be another mechanism responsible for the vasomotor disturbances in cold CRPS. An important goal in the treatment of cold‐type CRPS is the restoration of a normal blood flow. Consequently it is important to distinguish the underlying pathophysiological mechanisms of vasomotor disturbances. A disturbance of the sympathetic nervous system may require another type of treatment than inflammation‐induced endothelial dysfunction. Diagnostic tools to distinguish these underlying pathophysiological mechanisms of vasomotor disturbances would enable a mechanism‐based treatment and improve clinical outcome.
A Novel Compound Analgesic Cream (Ketamine, Pentoxifylline, Clonidine, DMSO) for Complex Regional Pain Syndrome Patients
Authors: Russo Marc A. , Santarelli Danielle M. 
Published: November 2015

AbstractBackgroundEvidence suggests that complex regional pain syndrome (CRPS) is a manifestation of microvascular dysfunction. Topical combinations of α2‐adrenergic receptor agonists or nitric oxide donors with phosphodiesterase or phosphatidic acid inhibitors formulated to treat microvascular dysfunction have been shown to reduce allodynia in a rat model of CRPS‐I. Driven by these findings, we assessed the outcomes of CRPS patients treated with a compound analgesic cream (CAC) consisting of ketamine 10%, pentoxifylline 6%, clonidine 0.2%, and dimethyl sulfoxide 6% to 10%.MethodsAn audit was conducted on 13 CRPS patients who trialed the CAC. A detailed report was compiled for each patient which comprised baseline characteristics, including CRPS description, previous treatments, and pain scores (numerical pain rating scale; 0 to 10). Recorded outcomes consisted of pain scores, descriptive outcomes, and concurrent medications/treatments, for which basic analysis was performed to determine the effectiveness of the CAC. Case reports are presented for 3 patients with varying outcomes.ResultsNine patients (69%) reported pain/symptom reduction (4.4 ± 2.1 vs. 6.3 ± 1.9) with use of the CAC. Six patients reported sustained benefits after 2 months of CAC use, and 2 patients reported complete resolution of pain/symptoms: one had early CRPS‐I and the other received a partial CRPS diagnosis. An otherwise medication refractory and intolerant patient found partial benefit with the CAC.ConclusionsThese results demonstrate promise for this topical combination as a useful treatment in multimodal therapy for patients with CRPS, with the potential to resolve pain/symptoms in early CRPS patients.