bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term effects of chronic nicotine on emotional and cognitive behaviors and hippocampus cell morphology in mice: comparisons of adult and adolescent nicotine exposure
Authors: Holliday Erica D. , Nucero Paul , Kutlu Munir G. , Oliver Chicora , Connelly Krista L. , Gould Thomas J. , Unterwald Ellen M. 
Published: September 2016

AbstractNicotine dependence is associated with increased risk for emotional, cognitive and neurological impairments later in life. This study investigated the long‐term effects of nicotine exposure during adolescence and adulthood on measures of depression, anxiety, learning and hippocampal pyramidal cell morphology. Mice (C57BL/6J) received saline or nicotine for 12 days via pumps implanted on postnatal day 32 (adolescent) or 54 (adults). Thirty days after cessation of nicotine/saline, mice were tested for learning using contextual fear conditioning, depression‐like behaviors using the forced swim test or anxiety‐like behaviors with the elevated plus maze. Brains from nicotine‐ or saline‐exposed mice were processed with Golgi stain for whole neuron reconstruction in the CA1 and CA3 regions of the hippocampus. Results demonstrate higher depression‐like responses in both adolescent and adult mice when tested during acute nicotine withdrawal. Heightened depression‐like behaviors persisted when tested after 30 days of nicotine abstinence in mice exposed as adolescents, but not adults. Adult, but not adolescent, exposure to nicotine resulted in increased open‐arm time when tested after 30 days of abstinence. Nicotine exposure during adolescence caused deficits in contextual fear learning indicated by lower levels of freezing to the context as compared with controls when tested 30 days later. In addition, reduced dendritic length and complexity in the apical CA1 branches in adult mice exposed to nicotine during adolescence were found. These results demonstrate that nicotine exposure and withdrawal can have long‐term effects on emotional and cognitive functioning, particularly when nicotine exposure occurs during the critical period of adolescence.
Manipulating virulence factor availability can have complex consequences for infections
Authors: Weigert Michael , Ross‐Gillespie Adin , Leinweber Anne , Pessi Gabriella , Brown Sam P. , Kümmerli Rolf 
Published: September 2016

AbstractGiven the rise of bacterial resistance against antibiotics, we urgently need alternative strategies to fight infections. Some propose we should disarm rather than kill bacteria, through targeted disruption of their virulence factors. It is assumed that this approach (i) induces weak selection for resistance because it should only minimally impact bacterial fitness, and (ii) is specific, only interfering with the virulence factor in question. Given that pathogenicity emerges from complex interactions between pathogens, hosts and their environment, such assumptions may be unrealistic. To address this issue in a test case, we conducted experiments with the opportunistic human pathogen Pseudomonas aeruginosa, where we manipulated the availability of a virulence factor, the iron‐scavenging pyoverdine, within the insect host Galleria mellonella. We observed that pyoverdine availability was not stringently predictive of virulence and affected bacterial fitness in nonlinear ways. We show that this complexity could partly arise because pyoverdine availability affects host responses and alters the expression of regulatorily linked virulence factors. Our results reveal that virulence factor manipulation feeds back on pathogen and host behaviour, which in turn affects virulence. Our findings highlight that realizing effective and evolutionarily robust antivirulence therapies will ultimately require deeper engagement with the intrinsic complexity of host–pathogen systems.
Molecular and histological characterization of age spots
Authors: Choi Wonseon , Yin Lanlan , Smuda Christoph , Batzer Jan , Hearing Vincent J. , Kolbe Ludger 
Published: September 2016

AbstractAge spots, also called solar lentigines and lentigo senilis, are light brown to black pigmented lesions of various sizes that typically develop in chronically sun‐exposed skin. It is well known that age spots are strongly related to chronic sun exposure and are associated with photodamage and an increased risk for skin cancer; however, the mechanisms underlying their development remain poorly understood. We used immunohistochemical analysis and microarray analysis to investigate the processes involved in their formation, focusing on specific markers associated with the functions and proliferation of melanocytes and keratinocytes. A total of 193 genes were differentially expressed in age spots, but melanocyte pigment genes were not among them. The increased expression of keratins 5 and 10, markers of basal and suprabasal keratinocytes, respectively, in age spots suggests that the increased proliferation of basal keratinocytes combined with the decreased turnover of suprabasal keratinocytes leads to the exaggerated formation of rete ridges in lesional epidermis which in turn disrupts the normal processing of melanin upwards from the basal layer. Based on our results, we propose a model for the development of age spots that explains the accumulation of melanin and the development of extensive rete ridges in those hyperpigmented lesions.
Membrane‐bound stem cell factor is the major but not only driver of fibroblast‐induced murine skin mast cell differentiation
Authors: Leist Mandy , Sünder Cathleen Annett , Drube Sebastian , Zimmermann Carolin , Geldmacher Astrid , Metz Martin , Dudeck Anne , Maurer Marcus 
Published: September 2016

AbstractThe maintenance and modulation of cutaneous mast cell (MC) numbers is held to be important for skin immune responses to allergens and pathogens. The increase in MC numbers in the skin is achieved by proliferation and the differentiation of precursor to mature MCs. Fibroblast‐derived SCF is thought to be the major skin MC growth factor and it potently induces MC proliferation. The mechanisms of fibroblast‐induced skin MC differentiation, including the role of SCF, however, remain insufficiently characterized and understood. Using cocultures of immature murine MCs and fibroblasts, we found that the adhesion of immature MCs to fibroblasts via VCAM‐1 and α4β7 integrin is very important for subsequent differentiation, which is driven by fibroblast membrane‐bound SCF and additional fibroblast‐derived membrane‐bound signals. Thus, our results show that fibroblast‐induced MC differentiation is induced by direct cell–cell contact and involves both Kit‐dependent and Kit‐independent pathways. Our findings add to the understanding of how immature mast cells mature in murine skin and encourage further analyses of the underlying mechanisms, which may result in novel targets for the modulation of skin mast cell driven diseases.
Metabolism of melatonin in the skin: Why is it important?
Authors: Slominski Andrzej T. , Semak Igor , Fischer Tobias W. , Kim Tae‐Kang , Kleszczyński Konrad , Hardeland Ruediger , Reiter Russel J. 
Published: September 2016

AbstractMelatonin is produced in almost all living taxa and is probably 2‐3 billion years old. Its pleiotropic activities are related to its local concentration that is secondary to its local synthesis, delivery from distant sites and metabolic or non‐enzymatic consumption. This consumption generates metabolites through indolic, kynuric and cytochrome P450 (CYP) mediated hydroxylations and O‐demethylation or non‐enzymatic processes, with potentially diverse phenotypic effects. While melatonin acts through receptor‐dependent and receptor‐independent mechanisms, receptors for melatonin metabolites remain to be identified, while their receptor‐independent activities are well documented. The human skin with its main cellular components including malignant cells can both produce and rapidly metabolize melatonin in cell‐type and context‐dependent fashion. The predominant metabolism in human skin occurs through indolic, CYP‐mediated and kynuric pathways with main metabolites represented by 6‐hydroxymelatonin, N1‐acetyl‐N2‐formyl‐5‐methoxykynuramine (AFMK), N1‐acetyl‐5‐methoxykynuramine (AMK), 5‐methoxytryptamine, 5‐methoxytryptophol and 2‐hydroxymelatonin. AFMK, 6‐hydroxymelatonin, 2‐hydroxymelatonin and probably 4‐hydroxymelatonin can potentially be produced in epidermis through UVB‐induced non‐enzymatic melatonin transformation. The skin metabolites are also the same as those produced in lower organisms and plants indicating phylogenetic conservation across diverse species and adaptation by skin of the primordial defense mechanism. As melatonin and its metabolites counteract or buffer environmental stresses to maintain its homeostasis through broad‐spectrum activities, both melatoninergic and degradative pathways must be precisely regulated, because the nature of phenotypic regulations will depend on local concentration of melatonin and its metabolites. These can be receptor‐mediated or represent non‐receptor regulatory mechanisms.
Proton‐sensing G protein‐coupled receptors as regulators of cell proliferation and migration during tumor growth and wound healing
Authors: Weiß Katharina T. , Fante Matthias , Köhl Gudrun , Schreml Julia , Haubner Frank , Kreutz Marina , Haverkampf Sonja , Berneburg Mark , Schreml Stephan 
Published: September 2016

AbstractDysregulation of pH is a feature of both tumor growth and tissue repair. In tumors, microenvironmental changes, like in lactate metabolism, lead to altered intra‐ and extracellular pH (pHi, pHe) and vice versa. In wounds, barrier disruption results in extensive variations in pHe on the wound surface. It is known that altered extracellular proton concentrations have a major impact on cell turnover and migration as well as on the metabolic activity of cells involved in tumor spread and wound closure. The proton‐sensing G protein‐coupled receptors (GPCRs) GPR4, GPR65 (TDAG8), GPR68 (OGR1) and GPR132 (G2A) are activated via a decrease in pHe and transduce this signal to molecular intracellular pathways. Based on the current knowledge, we speculate on the role of proton‐sensing GPCRs in wound healing and on their potential as mechanistic linkers of tumor growth and tissue repair.
Spatial and evolutionary parallelism between shade and drought tolerance explains the distributions of conifers in the conterminous United States
Authors: Rueda Marta , Godoy Oscar , Hawkins Bradford A. 
Published: September 2016

AbstractAimGymnosperms do not follow a latitudinal diversity gradient across the Northern Hemisphere but are influenced by geography at continental scales. Tolerance to physiological aridity is thought to be the main driver of this distribution, yet through evolutionary time conifers have also faced conditions of frost, shade and fire. We tested four predictions to evaluate how environmental stressors and geographical and evolutionary patterns of traits influence conifer distributions: (1) environmental variables related to aridity are most important in explaining geographical patterns of traits; (2) traits responsible for survival in stressful conditions have evolved under a niche conservatism constraint; (3) phylogenetic correlations among traits as the result of complex evolutionary responses to multiple abiotic stressors are widespread; (4) there are parallelisms between spatial trait associations and correlated trait evolution.LocationThe conterminous United States.MethodsWe combined conifer occurrences with 10 traits related to drought, freezing, shade and fire. The spatial distribution of traits was mapped and the relationship between environment and the geographical patterns of traits was explored. Niche conservatism was assessed comparing patterns of trait evolution against Brownian motion. We computed geographical and phylogenetic correlations among traits to determine the correspondence between spatial and evolutionary trade‐offs.Results(1) Maximum temperature followed by precipitation were the environmental variables that best described the geographical distributions of traits. (2) Most traits contain a phylogenetic signal consistent with niche conservatism: major exceptions being fire‐related traits and frost tolerance. (3) Drought and shade tolerances show one of the strongest negative phylogenetic correlations. (4) The drought–shade tolerance trade‐off is mirrored at the biogeographical scale.Main conclusionsUnlike in angiosperms, cold does not seem to have been a major driver in the evolutionary history of temperate conifers. A strong trade‐off between drought and shade tolerance is the simplest explanation for understanding the current distribution of conifers in North America.
The sign and magnitude of tree–grass interaction along a global environmental gradient
Authors: Mazía Noemí , Moyano Jaime , Perez Luis , Aguiar Sebastián , Garibaldi Lucas A. , Schlichter Tomas 
Published: September 2016

AbstractAimThe ecological literature posits that positive interactions are preponderant in stressful environments; however, the net balance between positive and negative interactions at the community level is still under debate. This study analysed the effect of trees on grass biomass in natural and cultivated woody systems distributed along a global aridity index (AI) gradient.LocationGlobal.MethodsWe conducted a meta‐analysis including eight natural biomes and tree plantations distributed in five continents. The final database consisted of 93 data pairs across 65 locations spanning a gradient from AI = 0.1 to AI = 2.1, which covered annual precipitation ranging from 70 to 3500 mm. Effect size was calculated as the difference between above‐ground grass biomass beneath and outside the tree canopy. We built linear models to evaluate the importance of different biotic and abiotic variables as potential drivers of the effect size. Multimodel inference, based on the Akaike information criterion (AICc) was used to select the best models.ResultsThe whole data set shows a shift from net facilitation to net competition along an increasing AI gradient. AI had the highest relative importance in explaining the sign and magnitude of the effect size. Tree characteristics (deciduous–evergreen and leguminous–non‐leguminous) were the other predictive variables consistently included in almost all the 10 best models. Deciduous and leguminous trees enhanced grass biomass growing beneath them. Increasing soil sand content, C4 grasses and tropical and natural systems all increased the biomass of grasses growing beneath trees, but their relative importance was substantially lower than that of the AI and tree characteristics.Main conclusionsThe results of our global meta‐analysis showed that climatic context and the characteristics of benefactor trees both represent the main drivers of the sign and magnitude of tree–grass interactions. These findings may contribute to advancing knowledge of the mechanisms behind the global patterns.
Outcomes and predictors of response from an optimised, multidisciplinary intervention for chronic fatigue states
Authors: Sandler C. X. , Hamilton B. A. , Horsfield S. L. , Bennett B. K. , Vollmer‐Conna U. , Tzarimas C. , Lloyd A. R. 
Published: September 2016

BackgroundMedically unexplained chronic fatigue states are prevalent and challenging to manage. Cognitive behavioural therapy (CBT) and graded exercise therapy (GET) are effective in clinical trials. The evaluation of delivery in a standard healthcare setting is rare. An integrated treatment programme with individualised allocation of resources to patients’ needs was developed and implemented through an academic outpatient clinic. It was hypothesised that the programme would result in similar responses to those observed in the clinical trials.AimTo evaluate the outcomes of an integrated, 12‐week CBT and GET programme delivered by exercise physiologists and clinical psychologists.MethodsConsecutive eligible patients (n = 264) who met the diagnostic criteria for chronic fatigue syndrome or post‐cancer fatigue were evaluated with self‐report measures of fatigue, functional capacity and mood disturbance at baseline, end‐of‐treatment (12 weeks) and follow‐up (24 weeks). A semi‐structured interview recording the same parameters was conducted pre‐ and post‐treatment by an independent clinician. Primary outcome was analysed by repeated measures analysis of variance and predictors of response were analysed by logistic regression.ResultsThe intervention produced sustained improvements in symptom severity and functional capacity. A substantial minority of patients (35%) gained significant improvement, with male gender and higher pain scores at baseline predicting non‐response. A small minority of patients (3%) worsened.ConclusionThe manualised protocol of integrated CBT and GET was successfully implemented, confirming the generally positive findings of clinical trials. Assessment and treatment protocols are available for dissemination to allow standardised management. The beneficial effects described here provide the basis for ongoing studies to optimise the intervention further and better identify those most likely to respond.
Enhancing feedback and improving feedback: subjective perceptions, psychological consequences, behavioral outcomes
Authors: Sedikides Constantine , Luke Michelle A. , Hepper Erica G. 
Published: September 2016

AbstractThree experiments examined subjective perceptions, psychological consequences, and behavioral outcomes of enhancing versus improving feedback. Across experiments, feedback delivery and assessment were sequential (i.e., at each testing juncture) or cumulative (i.e., at the end of the testing session). Although enhancing feedback was seen as more satisfying than useful, and improving feedback was not seen as more useful than satisfying, perceptions differed as a function of short‐term versus long‐term feedback delivery and assessment. Overall, however, enhancing feedback was more impactful psychologically and behaviorally. Enhancing feedback engendered greater success consistency, overall satisfaction and usefulness, optimism, state self‐esteem, perceived ability, and test persistence intentions; improving feedback, on the other hand, engendered greater state improvement. The findings provide fodder for theory development and applications.
Oceanic currents drove population genetic connectivity of the brown alga Sargassum thunbergii in the north‐west Pacific
Authors: Li Jing‐Jing , Hu Zi‐Min , Gao Xu , Sun Zhong‐Min , Choi Han‐Gil , Duan De‐Lin , Endo Hikaru 
Published: September 2016

AbstractAimOceanic currents are among the most pervasive hydrodynamic features in shaping community dynamics, population connectivity and phylogeographical structure of intertidal species. Here, we test whether population structure and biogeographical gradients of genetic diversity in the brown alga Sargassum thunbergii are correlated with oceanic currents in the north‐west Pacific (NWP).LocationNorth‐west Pacific (25.07°N–43.36°N).MethodsNuclear internal transcribed spacer‐2 and mitochondrial cox3 sequences were obtained from 835 and 810 individuals of S. thunbergii respectively. Parsimony networks and phylogenetic trees (maximum parsimony and Bayesian inference) were constructed to evaluate phylogeographical structure. Pairwise FST estimates and analyses of molecular variance (AMOVA) at various hierarchical levels (latitude, longitude, marine provinces, biogeographical basins and zoogeographical zones) were conducted to elucidate population genetic differentiation. migrate software was used to estimate the number of migrants between adjacent populations.ResultsSeveral lines of evidence indicate that S. thunbergii is characterized by shallow population structure. Geographical distances do not correlate with population pairwise genetic differentiations. The corridor/stepping‐stone model‐based coalescent analyses reveal high levels of asymmetric gene flow among S. thunbergii populations, with the numbers of migrants largely corresponding to the directions of oceanic current systems in the NWP. Genetic signatures also indicate that Jeju Island, Korea might act as a transition zone for dispersal of S. thunbergii in the NWP driven by the Kuroshio Current, thus facilitating subsequent transportation northward into the Sea of Japan and the Yellow‐Bohai Sea.Main conclusionsPopulation genetic homogeneity in S. thunbergii was mainly structured by oceanic currents rather than palaeoclimatic events. Our study illustrates an important phylogeographical case of how coastal hydrodynamic factors contributed to population connectivity and geographical shifts of genetic diversity for marine organisms without a pelagic stage.
Termite mounds alter the spatial distribution of African savanna tree species: artefacts and real patterns
Authors: Sileshi Gudeta W. 
Published: September 2016

AbstractIn a recent issue (vol. 43) of the Journal of Biogeography, Davies et al. (2015) presented novel analyses of the spatial distribution of tree species around termite mounds in a South African savanna. However, some of their conclusions are not supported by the data. My aim in this correspondence is to point out some limitations of their analyses, stimulate cautious interpretation of their results and suggest better methods for future use.
Targeting EP4 downstream c‐Jun through ERK1/2‐mediated reduction of DNMT1 reveals novel mechanism of solamargine‐inhibited growth of lung cancer cells
Authors: Chen Yuqing , Tang Qing , Xiao Qian , Yang LiJun , Hann Swei S. 
Published: September 2016

AbstractLung cancer is the most common cancer and the leading cause of cancer deaths worldwide. We previously showed that solamargine, one natural phytochemicals from traditional plants, inhibited the growth of lung cancer cells through inhibition of prostaglandin E2 (PGE2) receptor EP4. However, the potential downstream effectors of EP4 involving in the anti‐lung cancer effects of solamargine still remained to be determined. In this study, we further verified that solamargine inhibited growth of non‐small‐cell lung cancer (NSCLC) cells in multiple cell lines. Mechanistically, solamargine increased phosphorylation of ERK1/2. Moreover, solamargine inhibited the protein expression of DNA methyltransferase 1 (DNMT1) and c‐Jun, which were abrogated in cells treated with MEK/ERK1/2 inhibitor (PD98059) and transfected with exogenously expressed DNMT1 gene, respectively. Interestingly, overexpressed DNMT1 gene antagonized the effect of solamargine on c‐Jun protein expression. Intriguingly, overexpressed c‐Jun blocked solamargine‐inhibited lung cancer cell growth, and feedback resisted the solamargine‐induced phosphorylation of ERK1/2. A nude mouse xenograft model implanted with lung cancer cells in vivo confirmed the results in vitro. Collectively, our results show that solamargine inhibits the growth of human lung cancer cells through reduction of EP4 protein expression, followed by increasing ERK1/2 phosphorylation. This results in decrease in DNMT1 and c‐Jun protein expressions. The inter‐correlations between EP4, DNMT1 and c‐Jun and feedback regulation of ERK1/2 by c‐Jun contribute to the overall responses of solamargine in this process. This study uncovers an additional novel mechanism by which solamargine inhibits growth of human lung cancer cells.