bluuebunny/crossref_metadata_2025_split huggingface dataset:
Melatonin and the theories of aging: a critical appraisal of melatonin's role in antiaging mechanisms
Authors: Hardeland Rüdiger 
Published: August 2013

AbstractThe classic theories of aging such as the free radical theory, including its mitochondria‐related versions, have largely focused on a few specific processes of senescence. Meanwhile, numerous interconnections have become apparent between age‐dependent changes previously thought to proceed more or less independently. Increased damage by free radicals is not only linked to impairments of mitochondrial function, but also to inflammaging as it occurs during immune remodeling and by release of proinflammatory cytokines from mitotically arrested,DNA‐damaged cells that exhibit the senescence‐associated secretory phenotype (SASP). Among other effects,SASPcan cause mutations in stem cells that reduce the capacity for tissue regeneration or, in worst case, lead to cancer stem cells. Oxidative stress has also been shown to promote telomere attrition. Moreover, damage by free radicals is connected to impaired circadian rhythmicity. Another nexus exists between cellular oscillators and metabolic sensing, in particular to the aging‐suppressorSIRT1, which acts as an accessory clock protein. Melatonin, being a highly pleiotropic regulator molecule, interacts directly or indirectly with all the processes mentioned. These influences are critically reviewed, with emphasis on data from aged organisms and senescence‐accelerated animals. The sometimes‐controversial findings obtained either in a nongerontological context or in comparisons of tumor with nontumor cells are discussed in light of evidence obtained in senescent organisms. Although, in mammals, lifetime extension by melatonin has been rarely documented in a fully conclusive way, a support of healthy aging has been observed in rodents and is highly likely in humans.
Delay in leaf senescence of Malus hupehensis by long‐term melatonin application is associated with its regulation of metabolic status and protein degradation
Authors: Wang Ping , Sun Xun , Chang Cong , Feng Fengjuan , Liang Dong , Cheng Lailiang , Ma Fengwang 
Published: August 2013

AbstractMelatonin has an important anti‐aging role in plant physiology. We tested the effects of long‐term melatonin exposure on metabolic status and protein degradation during natural leaf senescence in trees of Malus hupehensis Rehd. The 2‐month regular supplement of 100 μm melatonin to the soil once every 6 days altered the metabolic status and delayed protein degradation. For example, leaves from treated plants had significantly higher photosynthetic activity, chlorophyll concentrations, and levels of three photosynthetic end products (sorbitol, sucrose, and starch) when compared with the control. The significant inhibition of hexose (fructose and glucose) accumulation possibly regulated the signaling of MdHXK1, a gene for which expression was also repressed by melatonin during senescence. The plants also exhibited better preservation of their nitrogen, total soluble protein, and Rubisco protein concentrations than the control. The slower process of protein degradation might be a result of melatonin‐linked inhibition on the expression of apple autophagy‐related genes (ATGs). Our results are the first to provide evidence for this delay in senescence based on the metabolic alteration and protein degradation.
Telaprevir impairs renal function and increases blood ribavirin concentration during telaprevir/pegylated interferon/ribavirin therapy for chronic hepatitis C
Authors: Karino Y. , Ozeki I. , Hige S. , Kimura M. , Arakawa T. , Nakajima T. , Kuwata Y. , Sato T. , Ohmura T. , Toyota J. 
Published: August 2013

SummaryWe aimed to examine the relationship between renal dysfunction and anaemia that may develop during combination therapy involving pegylated interferon, ribavirin and telaprevir (PEG‐IFN/RBV/TVR) for the treatment of chronic hepatitis C. Sixty‐eight patients with genotype 1b high viral loads were treated with PEG‐IFN/RBV/TVR. Peg‐IFN and RBV doses were administered according to body weight. TVR was prescribed at 2250 mg/day for 44 patients and at 1500 mg/day for 24 patients who had low haemoglobin level (<12 g/dL). When anaemia had developed, the RBV dose was decreased. The serum TVR concentration at day 8 was measured, and the serum RBV concentration was measured serially. The estimated glomerular filtration rate (eGFR) was estimated to assess renal function. At week 1, serum TVR concentration was not correlated with a decrease in eGFR; however, the TVR dose, on a weight basis (mg/kg), and eGFR were correlated (r = 0.2691; P = 0.0265). Moreover, there was a negative correlation between eGFR and RBV serum concentration (r = −0.3694; P = 0.0025), and the serum RBV concentration and decrease in the haemoglobin were significantly correlated from week 1 to week 8. In triple therapy, the TVR dose per weight is correlated with a decline in renal function. Thus, the serum concentration of RBV increases, with a concomitant decrease in haemoglobin. It is important to adjust the doses of TVR and RBV to avoid excessive serum RBV levels and the development of severe anaemia, to achieve a good clinical effect.
Accurate Antemortem Diagnosis of Equine Protozoal Myeloencephalitis (EPM) Based on Detecting Intrathecal Antibodies againstSarcocystis neuronaUsing the SnSAG2 and SnSAG4/3ELISAs
Authors: Reed S.M. , Howe D.K. , Morrow J.K. , Graves A. , Yeargan M.R. , Johnson A.L. , MacKay R.J. , Furr M. , Saville W.J.A. , Williams N.M. 
Published: August 2013

BackgroundRecent work demonstrated the value of antigen‐specific antibody indices (AIand C‐value) to detect intrathecal antibody production againstSarcocystis neuronafor antemortem diagnosis of equine protozoal myeloencephalitis (EPM).ObjectivesThe study was conducted to assess whether the antigen‐specific antibody indices can be reduced to a simple serum : cerebrospinal fluid (CSF) titer ratio to achieve accurateEPMdiagnosis.AnimalsPaired serum andCSFsamples from 128 horses diagnosed by postmortem examination. The sample set included 44EPMcases, 35 cervical‐vertebral malformation (CVM) cases, 39 neurologic cases other thanEPMorCVM, and 10 non‐neurologic cases.MethodsAntibodies againstS. neuronawere measured in serum andCSFpairs using the SnSAG2 and SnSAG4/3 (SnSAG2, 4/3)ELISAs, and the ratio of each respective serum titer toCSFtiter was determined. Likelihood ratios and diagnostic sensitivity and specificity were calculated based on serum titers,CSFtiters, and serum : CSFtiter ratios.ResultsExcellent diagnostic sensitivity and specificity was obtained from the SnSAG2, 4/3 serum : CSFtiter ratio. Sensitivity and specificity of 93.2 and 81.1%, respectively, were achieved using a ratio cutoff of ≤100, whereas sensitivity and specificity were 86.4 and 95.9%, respectively, if a more rigorous cutoff of ≤50 was used. Antibody titers inCSFalso provided good diagnostic accuracy. Serum antibody titers alone yielded much lower sensitivity and specificity.Conclusions and Clinical ImportanceThe study confirms the value of detecting intrathecal antibody production for antemortem diagnosis ofEPM, and they further show that the antigen‐specific antibody indices can be reduced in practice to a simple serum : CSFtiter ratio.
Expression of Leptin and iNOS in Oral Melanomas in Dogs
Authors: Greene V.R. , Wilson H. , Pfent C. , Roethele J. , Carwile J. , Qin Y. , Grimm E. , Ellerhorst J.A. 
Published: August 2013

BackgroundOral melanoma (OM) in dogs is an aggressive malignancy, with clinical behavior resembling cutaneous melanomas in humans. Melanoma in humans is promoted by an inflammatory environment that is contributed to by leptin and inducible nitric oxide synthase (iNOS).ObjectiveTo determine if the patterns of leptin and iNOS expression are similar in OM in dogs and cutaneous melanomas in humans.AnimalsTwenty client‐owned dogs.MethodsRetrospective case study. Immunostaining of the OM tumors from each dog was scored for percentage and intensity of leptin and iNOS expression. Mitotic index was used as an indicator of tumor aggression.ResultsLeptin was detected in ≥75% of the tumor cells in specimens from 11 dogs. One tumor expressed leptin in ≤25% of the cells. The intensity of leptin expression was variable with 6, 9, and 5 cases exhibiting low‐, moderate‐, and high‐intensity staining, respectively. OM with the lowest percentage of iNOS positive cells displayed the highest mitotic indices (P = .006, ANOVA).Conclusions and Clinical ImportanceThe expression of leptin is a common finding in melanomas in dogs. These data suggest that the possibility of future clinical applications, such as measuring the concentrations of plasma leptin as a screening tool or leptin as a target for therapy. The relevance of iNOS is not as clear in dogs with OM, for which other directed therapeutics might be more appropriate.
A spatially predictive baseline for monitoring multivariate species occurrences and phylogenetic shifts in mediterranean southern Australia
Authors: Guerin Greg R. , Biffin Ed , Jardine Duncan I. , Cross Hugh B. , Lowe Andrew J. 
Published: August 2013

AbstractQuestionClimate change is driving shifts in the composition of vegetation but the lack of controls and confounding spatial factors pose challenges for detecting the climate signal in observed changes through time and space. We tested whether climate can be isolated as a driver of spatial vegetation composition at the landscape scale in mediterranean southern Australia by considering landscape factors (e.g. soil gradients) and spatial structure (relative geographic isolation). The aim was to develop principles for selecting spatial analogues for climate change and provide a spatially predictive baseline for monitoring.MethodsA landscape‐scale monitoring transect spanning 550 km was established. Whole community presence/absence of vascular plant species in plots was modelled as a multivariate response to environmental and spatial variables. Species and phylogenetic composition–environment relationships were also explored using indirect gradient approaches, partial correlations and distance decay models.ResultsA total of >2900 occurrences of >400 plant species were recorded. Relative vegetation composition was predicted by mean temperature and soil properties, such as electrical conductivity and texture. Spatial structure was critical, as decay in compositional similarity with geographic distance and spatial autocorrelation of nested plots were involved in turnover patterns. The rate of change in species composition with changes in temperature equated to complete species turnover within the habitats sampled.ConclusionsThe influence of climate on spatial variation in vegetation composition can be quantified, accounting for distance decay. Landscape gradients (particularly soil properties) tended to be orthogonal to climate and explained some turnover. Spatial analogues for climate change would need to be similar in soil properties and not too geographically distant. Composition resulting from more extreme climate change scenarios may have no spatial analogue due to the importance of neutral distance decay at larger spatial scales in determining compositional differences. We illustrate these principles with a sequence of warming, drying analogues. The spatial transect provides a framework for monitoring composition by directly incorporating temporal data and using spatial analysis to inform the expected direction of compositional shifts with climate change.
Ankyrin‐repeat proteins from sponge symbionts modulate amoebal phagocytosis
Authors: Nguyen Mary T. H. D. , Liu Michael , Thomas Torsten 
Published: August 2013

AbstractBacteria–eukaryote symbiosis occurs in all stages of evolution, from simple amoebae to mammals, and from facultative to obligate associations. Sponges are ancient metazoans that form intimate symbiotic interactions with complex communities of bacteria. The basic nutritional requirements of the sponge are in part satisfied by the phagocytosis of bacterial food particles from the surrounding water. How bacterial symbionts, which are permanently associated with the sponge, survive in the presence of phagocytic cells is largely unknown. Here, we present the discovery of a genomic fragment from an uncultured gamma‐proteobacterial sponge symbiont that encodes for four proteins, whose closest known relatives are found in a sponge genome. Through recombinant approaches, we show that these four eukaryotic‐like, ankyrin‐repeat proteins (ARP) when expressed in Eschericha coli can modulate phagocytosis of amoebal cells and lead to accumulation of bacteria in the phagosome. Mechanistically, two ARPs appear to interfere with phagosome development in a similar way to reduced vacuole acidification, by blocking the fusion of the early phagosome with the lysosome and its digestive enzymes. Our results show that ARP from sponge symbionts can function to interfere with phagocytosis, and we postulate that this might be one mechanism by which symbionts can escape digestion in a sponge host.
Phenotypic plasticity in the hepatic transcriptome of the European common frog (Rana temporaria): the interplay between environmental induction and geographical lineage on developmental response
Authors: Johansson Frank , Veldhoen Nik , Lind Martin I. , Helbing Caren C. 
Published: August 2013

AbstractPhenotypic plasticity might facilitate adaptation to new environmental conditions through the enhancement of initial survival of organisms. Once a population is established, further adaptation and diversification may occur through adaptive trait evolution. While several studies have found evidence for this mechanism using phenotypic traits, much less is known at the level of gene expression. Here, we use an islands system of frog populations that show local adaptation and phenotypic plasticity to pool drying conditions in development time until metamorphoses. We examined gene expression differences in Rana temporaria tadpole livers with respect to pool drying at the source population and in response to simulated pool drying in the laboratory. Using a MAGEX cDNA microarray and quantitative real‐time polymerase chain reaction (qPCR), we identified an increase in several gene transcripts in response to artificial pool drying including thyroid hormone receptor alpha and beta, carbamoyl phosphate synthetase 1, ornithine transcarbamylase and catalase. In addition, these gene transcripts also showed greater abundance in island populations that developed faster. Hence, the gene transcripts were related to both constitutive response (higher levels in island populations that developed faster) and plastic response (increased abundance under decreasing water levels). This pattern is in accordance with genetic accommodation, which predicts similarities between plastic gene expression and constitutive expression in locally adapted populations.
Defect Detection in Reinforced Concrete Using Random Neural Architectures
Authors: Butcher J.B. , Day C.R. , Austin J.C. , Haycock P.W. , Verstraeten D. , Schrauwen B. 
Published: August 2013

AbstractDetecting defects within reinforced concrete is vital to the safety and durability of our built infrastructure upon which we heavily rely. In this work a non‐invasive technique, ElectroMagnetic Anomaly Detection (EMAD), is used which provides information into the electromagnetic properties of the reinforcing steel and for which data analysis is currently performed visually: an undesirable process. This article investigates the first use of two neural network approaches to automate the analysis of this data: Echo State Networks (ESNs) and Extreme Learning Machines (ELMs) where fast and efficient training procedures allow networks to be trained and evaluated in less time than traditional neural network approaches. Data collected from real‐world concrete structures have been analyzed using these two approaches as well as using a simple threshold measure and a standard recurrent neural network. The ELM approach offers a significant improvement in performance for a single tendon‐reinforced structure, while two ESN architectures provided best performance for a mesh‐reinforced concrete structure.
Trypanosoma brucei (UMP synthase null mutants) are avirulent in mice, but recover virulence upon prolonged culture in vitro while retaining pyrimidine auxotrophy
Authors: Ong Han B. , Sienkiewicz Natasha , Wyllie Susan , Patterson Stephen , Fairlamb Alan H. 
Published: August 2013

SummaryAfrican trypanosomes are capable of both de novo synthesis and salvage of pyrimidines. The last two steps in de novo synthesis are catalysed by UMP synthase (UMPS) – a bifunctional enzyme comprising orotate phosphoribosyl transferase (OPRT) and orotidine monophosphate decarboxylase (OMPDC). To investigate the essentiality of pyrimidine biosynthesis in Trypanosoma brucei, we generated a umps double knockout (DKO) line by gene replacement. The DKO was unable to grow in pyrimidine‐depleted medium in vitro, unless supplemented with uracil, uridine, deoxyuridine or UMP. DKO parasites were completely resistant to 5‐fluoroorotate and hypersensitive to 5‐fluorouracil, consistent with loss of UMPS, but remained sensitive to pyrazofurin indicating that, unlike mammalian cells, the primary target of pyrazofurin is not OMPDC. The null mutant was unable to infect mice indicating that salvage of host pyrimidines is insufficient to support growth. However, following prolonged culture in vitro, parasites regained virulence in mice despite retaining pyrimidine auxotrophy. Unlike the wild‐type, both pyrimidine auxotrophs secreted substantial quantities of orotate, significantly higher in the virulent DKO line. We propose that this may be responsible for the recovery of virulence in mice, due to host metabolism converting orotate to uridine, thereby bypassing the loss of UMPS in the parasite.
Overexpression ofGmCaM4in soybean enhances resistance to pathogens and tolerance to salt stress
Authors: Rao Suryadevara S. , El‐Habbak Mohamed H. , Havens Wendy M. , Singh Ajay , Zheng Danman , Vaughn Laura , Haudenshield James S. , Hartman Glen L. , Korban Schuyler S. , Ghabrial Said A. 
Published: August 2013

SummaryPlant diseases inflict heavy losses on soybean yield, necessitating an understanding of the molecular mechanisms underlying biotic/abiotic stress responses.Ca2+is an important universal messenger, and protein sensors, prominently calmodulins (CaMs), recognize cellular changes inCa2+in response to diverse signals. Because the development of stable transgenic soybeans is laborious and time consuming, we used theBean pod mottle virus(BPMV)‐based vector for rapid and efficient protein expression and gene silencing. The present study focuses on the functional roles of the gene encoding the soybean CaM isoformGmCaM4. Overexpression ofGmCaM4in soybean resulted in enhanced resistance to three plant pathogens and increased tolerance to high salt conditions. To gain an understanding of the underlying mechanisms, we examined the potential defence pathways involved. Our studies revealed activation/increased expression levels of pathogenesis‐related (PR) genes inGmCaM4‐overexpressing plants and the accumulation of jasmonic acid (JA). Silencing ofGmCaM4, however, markedly repressed the expression ofPRgenes. We confirmed thein vivointeraction betweenGmCaM4and theCaMbinding transcription factorMyb2, which regulates the expression of salt‐responsive genes, using the yeast two‐hybrid (Y2H) system and bimolecular fluorescence complementation assays.GmCaM4andGlycine max CaMbinding receptor‐like kinase (GmCBRLK) did not interact in theY2Hassays, but the interaction betweenGmCaM2andGmCBRLKwas confirmed. Thus, aGmCaM2–GmCBRLK‐mediated salt tolerance mechanism, similar to that reported inGlycine soja, may also be functional in soybean. Confocal microscopy showed subcellular localization of the green fluorescent protein (GFP)‐GmCaM4fusion protein in the nucleus and cytoplasm.
Temporal Stability in the Spectral Representation of Complex Fractionated Atrial Electrograms
Authors: CIACCIO EDWARD J. , BIVIANO ANGELO B. , GAMBHIR ALOK , JACOBSON JASON T. , GARAN HASAN 
Published: August 2013

BackgroundAlthough local electrograms during atrial fibrillation (AF) are often spectrally analyzed over 8‐second (8s) intervals, changes may be common over intervals as short as 2s. We sought to determine whether averaged 2s measurements of electrogram spectral parameters were similar to 8s measurements, and whether the 2s intervals could provide an estimate of the temporal stability of the signal frequency content in paroxysmal versus persistent AF.MethodsComplex fractionated atrial electrograms (CFAEs) were acquired outside the pulmonary vein ostia and from free wall sites in nine paroxysmal and 10 longstanding persistent AF patients. Using a 2s sliding calculation window, a frequency spectrum was computed every 100 ms over an interval of 8.4 seconds (82 spectra in total). The dominant frequency (DF), the dominant amplitude (DA), and the mean spectral profile (MP) were measured. The 2s measurements were compared to single 8.4‐second interval measurements. Coefficients of variation (COV) were computed from the 82 spectra for each CFAE recording to determine temporal variability of parameters.ResultsOver the sliding 2s computation intervals, as for fixed 8.4‐second computation intervals, mean DA and DF were significantly higher in longstanding persistent AF while MP was significantly higher in paroxysmal AF (P ≤ 0.001). The COV was significantly higher for the DF parameter in paroxysmal AF (P < 0.001) and significantly higher for the MP parameter in persistent AF (P < 0.02).ConclusionsFor both paroxysmal and persistent AF data, the 2s sliding window averages provide similar results to single 8.4‐second intervals, and information regarding temporal stability was additionally obtained in the process.
Anesthesia management with single injection paravertebral block for aorta coarctation in infant
Authors: Türköz Ayda , Balcı Sule T. , Can Güner Meltem , Ulugöl Halim , Vuran Can , Özker Emre , Türköz Rıza 
Published: August 2013

SummaryBackgroundThoracotomy causes severe pain in the postoperative period. Perioperative thoracic paravertebral block reduces pain score and may improve outcome after pediatric cardiac surgery. This prospective study was designed for the efficacy and duration of a single level, single injection ultrasound–guided thoracic paravertebral block (TPVB) for fifteen infants undergoing aortic coarctation repair.MethodsAfter approval of the ethical committee and the relatives of the patients, 15 infants who had undergone thoracotomy were enrolled in the study. The patients received 0.5 ml·kg−1 a bolus 0.25% bupivacaine with epinephrine 1 : 200 000 at T5‐6 level after standard general anesthesia induction. Anesthesia depth with Index of Consciousness (IOC) and tissue oxygen saturation with cerebral (rSO2‐C) and somatic thoracodorsal (rSO2‐S) were monitored. Intraoperative hemodynamic and postoperative hemodynamic and pain scores were evaluated for 24 h after surgery. Face, Legs, Activity, Cry, Consolability (FLACC) score was utilized to measure postoperative pain in the intensive care unit. Rescue 0.05 mg·kg−1 IV morphine was applied to patients in whom FLACC was >3.ResultsThe median age of the patients was 4.5 (1–11) months, and the median intraoperative endtidal isoflurane concentration was 0.6% (0.3–0.8). The amount of remifentanil used intraoperatively was 4.5 (2.5–14) μg·kg−1·h−1. Intraoperative heart rate and blood pressure values significantly decreased compared with values detected at 5th, 10th, and 15th min after TPVB application, after incision prior and after cross‐clamp (P < 0.01). The median time of first dose of morphine application after block was 320 (185–430) min. The median morphine consumption in 24 h was 0.16 (0.09–0.4) mg·kg−1. The median length of postoperative intensive care unit and in‐hospital stay times was 23 (1–67) h and 4 (1–10) days, respectively.ConclusionWe believe that TPVB, as part of a balanced anesthetic and analgesic regime, provides effective pain relief in patients undergoing aortic coarctation repair.