bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive cytotoxic evaluation of morin, a bioflavonoid against verapamil on rat gastrointestinal epithelium for novel pharmaceutical application involving P-glycoprotein inhibition
Authors: Surampalli Gurunath , Nanjwade Basavaraj K , Patil Paragouda A 
Published: April 2015

Abstract

Objective
In this study, a comprehensive and comparative cytotoxic evaluation of morin against verapamil on rat intestinal epithelium as P-gp inhibitors through in-vitro gastrointestinal short-term toxicity assays involving permeability studies for safety evaluation was investigated.

Methods
In this study, the effect of morin (1 mM or 10 mM) or verapamil (1 mM or 10 mM) or sodium deoxycholate (10 mM) was investigated on intestinal epithelium and isolated brush border membrane using biomarker assays. Cytotoxicity was determined using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay. The nutrients transport was assessed using everted sacs studies. Paracellular permeability was measured using Lucifer yellow, followed by morphometric analysis of intestinal sacs.

Key findings
Our results indicated that morin was effective in maintaining cell viability with no significant changes (P &gt; 0.05) in the activity of intestinal brush border markers, membrane integrity and morphometric analysis as compared with control. On the contrary, dramatic (P &lt; 0.01) changes were noticed in the release of membrane markers, cell viability and surface characteristics of intestinal segments when treated with verapamil or sodium deoxycholate as compared with control or morin.

Conclusions
Our findings confirm that morin is non-toxic to rat intestinal epithelium against verapamil demonstrating the potential use of bioflavonoid as safe and novel pharmaceutical adjuvant as P-gp inhibitor.
Spray-dried extract of Phyllanthus niruri L. reduces mucosal damage in rats with intestinal inflammation
Authors: Nunes de Melo Maryanne , Alberto Lira Soares Luiz , Raquel da Costa Porto Cynthia , Antunes de Araújo Aurigena , das Graças Almeida Maria , Pereira de Souza Tatiane , Petrovick Pedro Ros , Fernandes de Araújo Raimundo , Guerra Gerlane Coelho Bernardo 
Published: April 2015

Abstract

Phyllanthus niruri L. belongs to the Euphorbiaceae, and is known by the common name of ‘stonebreaker’ in Brazil. Some species within the Phyllanthus genus are widely used in traditional medicine to counteract different types of anti-inflammatory diseases.

Objectives
In this study, the preventive intestinal anti-inflammatory activity of spray-dried extract of P. niruri (SDEPn) was tested in the model of acetic acid (10%)-induced ulcerative colitis in the rat.

Methods
Colitis animals were given orally at doses 25, 100 and 200 mg/kg. Colons tissue was analysed by macroscopic score, by histopathology score, by the immunohistochemical examination of tumour necrosis factor alpha, p53 and interferon gamma; by spectroscopic ultraviolet-visible spectrophotometry (UV/VIS) analysis of the levels of myeloperoxidase, malonaldehyde and total glutathione.

Key Findings/Result
Pretreatment of the extract to colitic rats significantly attenuated colonic macroscopic damage induced by acetic acid (P &lt; 0.01). Spray-dried extract of P. niruri prevented glutathione depletion (P &lt; 0.001) and malondialdehyde levels (P &lt; 0.05) declined. Spray-dried extract of P. niruri significantly reduced microscopic damage to tissues, such as leukocyte infiltration accompanied by a significant reduction in myeloperoxidase activity (P &lt; 0.5). Immunohistochemistry revealed a decline in the TNF-α, IFN-γ and p53 protein (P &lt; 0.05).

Conclusion
Spray-dried extract of P. niruri has a beneficial effect in the acute phase of acetic acid-induced colitis in the rat, which is probably related to its antioxidant properties.
The effect of canola meal tannins on the intestinal absorption capacity of broilers using a D‐xylose test
Authors: Mansoori B. , Rogiewicz A. , Slominski B. A. 
Published: April 2015

SummaryIn three D‐xylose absorption experiments, the effect of 1% HCl/methanol, 70% methanol or 70% acetone extracts of canola meal (CM) or 70% acetone extract of soybean meal (SBM) containing polyphenols, phenolic acids, tannins and phytic acid on intestinal absorption capacity of broilers was determined. In Exp. 1, the experimental groups received orally D‐xylose solution alone or with methanol/HCl, methanol or acetone extracts of CM. In Exp. 2, the experimental groups received D‐xylose alone or with acetone extracts of CM or SBM. In Exp. 3, the experimental groups received D‐xylose plus sucrose solution or D‐xylose plus acetone extracts of CM or SBM. In Exps. 2 and 3, the CM extracts contained 2.7 and 2.6, 2.4 and 2.3, 3.2 and 3.2, and 2.4 and 2.2 times higher polyphenols, phenolic acids, tannins and condensed tannins than the corresponding SBM extracts respectively. Blood samples were collected in 40‐min intervals, and plasma D‐xylose was measured. Compared to the Control, plasma D‐xylose in Exp. 1 was lower (p < 0.001) by 81, 69 and 73% at 40‐min, by 41, 44 and 37% at 80‐min and by 22, 31, and 23% at 120‐min post‐ingestion of the HCl/methanol, methanol and acetone extracts respectively. In both Exps. 2 and 3, plasma D‐xylose level was lower (p < 0.001) in groups dosed with CM extract or SBM extract at each time of blood collection, when compared to the respective Control group. However, in Exp. 3, birds dosed with SBM extract had higher plasma D‐xylose than CM extract‐dosed birds by 28, 8 and 21% at 40, 80 and 120 min respectively (p < 0.01). In conclusion, although CM extract caused a lower absorption of D‐xylose, based on 5 to 10% of CM inclusion levels in practical broiler rations, the soluble bioactive components of CM will likely have minor impact on the absorption capacity of the chicken intestine.
Detection of adrenomedullin and nitric oxide in different forms of periodontal disease
Authors: Hussain Q. A. , McKay I. J. , Gonzales‐Marin C. , Allaker R. P. 
Published: April 2015

Background and ObjectiveThe multifunctional molecules adrenomedullin (AM) and nitric oxide (NO) are both involved in the host response to microbial challenge during periodontal disease. Whether they coexist in periodontal inflammation and if equally produced in the different forms of periodontal disease has not previously been investigated. The aims of this study were to describe the locations of AM and NO in healthy and inflamed gingival tissues and to determine and compare their levels in the gingival crevicular fluid and saliva of patients with gingivitis, chronic periodontitis and aggressive periodontitis.Material and MethodsAM and inducible nitric oxide synthase (iNOS) were immunolocalized in clinically healthy and inflamed gingival tissue sections. The cells expressing AM and iNOS were characterized using immunocytochemistry with different markers for macrophages [cluster differentiation (CD)68 and CD14)], dendritic cells (CD83), neutrophils [neutrophil gelatinase‐associated lipocalin (nGAL)] and natural killer cells (CD56). In an initial study, the levels of AM and NO were also measured in samples of gingival crevicular fluid and saliva obtained from patients with a diagnosis of gingivitis (n = 9), chronic periodontitis (n = 9) and aggressive periodontitis (n = 9) using an ELISA and the nitrate/nitrite (NO metabolites) Griess assay, respectively.ResultsLow levels of AM‐ and iNOS‐expressing cells were detected in healthy gingival tissues in comparison with three‐fold higher levels of these cells in inflamed tissues. These cells were localized mainly in the epithelial layer but were also present in deeper connective tissue. AM and iNOS were co‐localized in particular cells within inflamed tissues, namely CD68+(52%) and CD14+ (36%) macrophages, but also in nGAL+ neutrophils (16%) and CD83+ dendritic cells (14%). Interestingly, AM and NO levels in saliva were both found to be higher (p < 0.01) in patients with aggressive periodontitis than in patients with chronic periodontitis or gingivitis. In contrast, in gingival crevicular fluid, the levels of NO showed marked differences among patients with chronic periodontitis, aggressive periodontitis and gingivitis (p < 0.01), and the levels of AM were higher (p < 0.01) in both chronic and aggressive periodontitis compared with gingivitis alone.ConclusionThe data presented demonstrate a functional linkage between AM and NO in periodontal disease, with salivary and gingival crevicular fluid levels possibly associated with different forms and severities of periodontal disease. Exacerbated production of both AM and NO in saliva suggests their potential use as salivary markers of aggressive periodontitis.
Right hemisphere neural activations in the recall of waking fantasies and of dreams
Authors: Benedetti Francesco , Poletti Sara , Radaelli Daniele , Ranieri Rebecca , Genduso Valeria , Cavallotti Simone , Castelnovo Anna , Smeraldi Enrico , Scarone Silvio , D'Agostino Armando 
Published: April 2015

SummaryThe story‐like organization of dreams is characterized by a pervasive bizarreness of events and actions that resembles psychotic thought, and largely exceeds that observed in normal waking fantasies. Little is known about the neural correlates of the confabulatory narrative construction of dreams. In this study, dreams, fantasies elicited by ambiguous pictorial stimuli, and non‐imaginative first‐ and third‐person narratives from healthy participants were recorded, and were then studied for brain blood oxygen level‐dependent functional magnetic resonance imaging on a 3.0‐Tesla scanner while listening to their own narrative reports and attempting a retrieval of the corresponding experience. In respect to non‐bizarre reports of daytime activities, the script‐driven recall of dreams and fantasies differentially activated a right hemisphere network including areas in the inferior frontal gyrus, and superior and middle temporal gyrus. Neural responses were significantly greater for fantasies than for dreams in all regions, and inversely proportional to the degree of bizarreness observed in narrative reports. The inferior frontal gyrus, superior and middle temporal gyrus have been implicated in the semantic activation, integration and selection needed to build a coherent story representation and to resolve semantic ambiguities; in deductive and inferential reasoning; in self‐ and other‐perspective taking, theory of mind, moral and autobiographical reasoning. Their degree of activation could parallel the level of logical robustness or inconsistency experienced when integrating information and mental representations in the process of building fantasy and dream narratives.
A jack of all trades: the multiple roles of the unique essential second messenger cyclic di‐AMP
Authors: Commichau Fabian M. , Dickmanns Achim , Gundlach Jan , Ficner Ralf , Stülke Jörg 
Published: April 2015

SummarySecond messengers are key components of many signal transduction pathways. In addition to cyclicAMP, ppGpp and cyclic di‐GMP, many bacteria use also cyclic di‐AMPas a second messenger. This molecule is synthesized by distinct classes of diadenylate cyclases and degraded by phosphodiesterases. The control of the intracellular c‐di‐AMPpool is very important since both a lack of this molecule and its accumulation can inhibit growth of the bacteria. In many firmicutes, c‐di‐AMPis essential, making it the only known essential second messenger. Cyclic di‐AMPis implicated in a variety of functions in the cell, including cell wall metabolism, potassium homeostasis,DNArepair and the control of gene expression. To understand the molecular mechanisms behind these functions, targets of c‐di‐AMPhave been identified and characterized. Interestingly, c‐di‐AMPcan bind both proteins andRNAmolecules. Several proteins that interact with c‐di‐AMPare required to control the intracellular potassium concentration. InBacillus subtilis, c‐di‐AMPalso binds a riboswitch that controls the expression of a potassium transporter. Thus, c‐di‐AMPis the only known second messenger that controls a biological process by interacting with both a protein and the riboswitch that regulates its expression. Moreover, inListeria monocytogenesc‐di‐AMPcontrols the activity of pyruvate carboxylase, an enzyme that is required to replenish the citric acid cycle. Here, we review the components of the c‐di‐AMPsignaling system.
Below‐ground abiotic and biotic heterogeneity shapes above‐ground infection outcomes and spatial divergence in a host–parasite interaction
Authors: Tack Ayco J. M. , Laine Anna‐Liisa , Burdon Jeremy J. , Bissett Andrew , Thrall Peter H. 
Published: April 2015

Summary

We investigated the impact of below‐ground and above‐ground environmental heterogeneity on the ecology and evolution of a natural plant–pathogen interaction.

We combined field measurements and a reciprocal inoculation experiment to investigate the potential for natural variation in abiotic and biotic factors to mediate infection outcomes in the association between the fungal pathogen Melampsora lini and its wild flax host, Linum marginale, where pathogen strains and plant lines originated from two ecologically distinct habitat types that occur in close proximity (‘bog’ and ‘hill’).

The two habitat types differed strikingly in soil moisture and soil microbiota. Infection outcomes for different host–pathogen combinations were strongly affected by the habitat of origin of the plant lines and pathogen strains, the soil environment and their interactions. Our results suggested that tradeoffs play a key role in explaining the evolutionary divergence in interaction traits among the two habitat types.

Overall, we demonstrate that soil heterogeneity, by mediating infection outcomes and evolutionary divergence, can contribute to the maintenance of variation in resistance and pathogenicity within a natural host–pathogen metapopulation.
Betalain induction by l‐DOPA application confers photoprotection to saline‐exposed leaves of Disphyma australe
Authors: Jain Gagandeep , Schwinn Kathy E. , Gould Kevin S. 
Published: April 2015

Summary

The capacity to synthesize betalains has arisen in diverse phylogenetic lineages across the Caryophyllales, and because betalainic plants often grow in deserts, sand dunes, or salt marshes, it is likely that these pigments confer adaptive advantages. However, possible functional roles of foliar betalains remain largely unexplored and are difficult to test experimentally. We adopted a novel approach to examine putative photoprotective roles of betalains in leaves for which chloroplast function has been compromised by salinity.

Responses of l‐DOPA‐treated red shoots of Disphyma australe to high light and salinity were compared with those of naturally red‐ and green‐leafed morphs. Betalain content and tyrosinase activity were measured, and Chl fluorescence profiles and H2O2 production were compared under white, red or green light.

Green leaves lacked tyrosinase activity, but when supplied with exogenous l‐DOPA they produced five betacyanins. Both the naturally red and l‐DOPA‐induced red leaves generated less H2O2 and showed smaller declines in photosystem II quantum efficiency than did green leaves when exposed to white or green light, although not when exposed to red light.

Light screening by epidermal betalains effectively reduces the propensity for photoinhibition and photo‐oxidative stress in subjacent chlorenchyma. This may assist plant survival in exposed and saline environments.
Ontogenetic and interspecific scaling of consumption in insects
Authors: Maino James L. , Kearney Michael R. 
Published: April 2015

The uptake of resources from the environment is a basic feature of all life. Consumption rate has been found to scale with body size with an exponent close to unity across diverse organisms. However, past analyses have ignored the important distinction between ontogenetic and interspecific size comparisons. Using principles of dynamic energy budget theory, we present a mechanistic model for the body mass scaling of consumption, which separates interspecific size effects from ontogenetic size effects. Our model predicts uptake to scale with surface‐area (mass2/3) during ontogenetic growth but more quickly (between mass3/4 and mass1) for interspecific comparisons. Available data for 41 insect species on consumption and assimilation during ontogeny provides strong empirical support for our theoretical predictions. Specifically, consumption rate scaled interspecifically with an exponent close to unity (0.89) but during ontogenetic growth scaled more slowly with an exponent of 0.70. Assimilation rate (consumption minus defecation) through ontogeny scaled more slowly than consumption due to a decrease in assimilation efficiency as insects grow. Our results highlight how body size imposes different constraints on metabolism depending on whether the size comparison is ontogenetic or inter‐specific.SynthesisOne of the most robust patterns in biology is the effect of body size on metabolism – a relationship that underlies the rapidly emerging field of metabolic ecology. However, the precise energetic constraints imposed by body size have been notoriously difficult to entangle. Here we show that the constraints imposed on metabolism by body size are different depending on whether the size comparison is ontogenetic or interspecific. Using a single unifying theory of animal metabolism and a newly compiled data set on insect consumption and assimilation rates, we show that interspecific comparisons generally lead to the estimation of higher scaling exponents compared with ontogenetic comparisons. Our results help to explain large variation in estimated metabolic scaling exponents and will encourage future studies in metabolic ecology to make the important distinction between ontogenetic and evolutionary size changes.
The role of phagocytosis, oxidative burst and neutrophil extracellular traps in the interaction between neutrophils and the periodontal pathogen Porphyromonas gingivalis
Authors: Jayaprakash K. , Demirel I. , Khalaf H. , Bengtsson T. 
Published: April 2015

SummaryNeutrophils are regarded as the sentinel cells of innate immunity and are found in abundance within the gingival crevice. Discovery of neutrophil extracellular traps (NETs) within the gingival pockets prompted us to probe the nature of the interactions of neutrophils with the prominent periopathogen Porphyromonas gingivalis. Some of the noted virulence factors of this Gram‐negative anaerobe are gingipains: arginine gingipains (RgpA/B) and lysine gingipain (Kgp). The aim of this study was to evaluate the role of gingipains in phagocytosis, formation of reactive oxygen species, NETs and CXCL8 modulation by using wild‐type strains and isogenic gingipain mutants. Confocal imaging showed that gingipain mutants K1A (Kgp) and E8 (RgpA/B) induced extracellular traps in neutrophils, whereas ATCC33277 and W50 were phagocytosed. The viability of both ATCC33277 and W50 dwindled as the result of phagocytosis and could be salvaged by cytochalasin D, and the bacteria released high levels of lipopolysaccharide in the culture supernatant. Porphyromonas gingivalis induced reactive oxygen species and CXCL8 with the most prominent effect being that of the wild‐type strain ATCC33277, whereas the other wild‐type strain W50 was less effective. Quantitative real‐time polymerase chain reaction revealed a significant CXCL8 expression by E8. All the tested P. gingivalis strains increased cytosolic free calcium. In conclusion, phagocytosis is the primary neutrophil response to P. gingivalis, although NETs could play an accessory role in infection control. Although gingipains do not seem to directly regulate phagocytosis, NETs or oxidative burst in neutrophils, their proteolytic properties could modulate the subsequent outcomes such as nutrition acquisition and survival by the bacteria.
TALEN‐mediated targeted mutagenesis produces a large variety of heritable mutations in rice
Authors: Zhang Hui , Gou Feng , Zhang Jinshan , Liu Wenshan , Li Qianqian , Mao Yanfei , Botella José Ramón , Zhu Jian‐Kang 
Published: April 2015

SummaryCRISPR/Cas9 and TALEN are currently the two systems of choice for genome editing. We have studied the efficiency of the TALEN system in rice as well as the nature and inheritability of TALEN‐induced mutations and found important features of this technology. The N287C230 TALEN backbone resulted in low mutation rates (0–6.6%), but truncations in its C‐terminal domain dramatically increased efficiency to 25%. In most transgenic T0 plants, TALEN produced a single prevalent mutation accompanied by a variety of low‐frequency mutations. For each independent T0 plant, the prevalent mutation was present in most tissues within a single tiller as well as in all tillers examined, suggesting that TALEN‐induced mutations occurred very early in the development of the shoot apical meristem. Multigenerational analysis showed that TALEN‐induced mutations were stably transmitted to the T1 and T2 populations in a normal Mendelian fashion. In our study, the vast majority of TALEN‐induced mutations (~81%) affected multiple bases and ~70% of them were deletions. Our results contrast with published reports for the CRISPR/Cas9 system in rice, in which the predominant mutations affected single bases and deletions accounted for only 3.3% of the overall mutations.
Helminths and the microbiota: parts of the hygiene hypothesis
Authors: Loke P. , Lim Y. A. L. 
Published: April 2015

SummaryIn modern societies, diseases that are driven by dysregulated immune responses are increasing at an alarming pace, such as inflammatory bowel diseases and diabetes. There is an urgent need to understand these epidemiological trends, which are likely to be driven by the changing environment of the last few decades. There are complex interactions between human genetic factors and this changing environment that is leading to the increasing prevalence of metabolic and inflammatory diseases. Alterations to human gut bacterial communities (the microbiota) and lowered prevalence of helminth infections are potential environmental factors contributing to immune dysregulation. Helminths have co‐evolved with the gut microbiota and their mammalian hosts. This three‐way interaction is beginning to be characterized, and the knowledge gained may enable the design of new therapeutic strategies to treat metabolic and inflammatory diseases. However, these complex interactions need to be carefully investigated in the context of host genetic backgrounds to identify optimal treatment strategies. The complex nature of these interactions raises the possibility that only with highly personalized treatment, with knowledge of individual genetic and microbiota communities, will therapeutic interventions be successful for a majority of the individuals suffering from these complex diseases of immune dysregulation.