bluuebunny/crossref_metadata_2025_split huggingface dataset:
Melatonin down‐regulates MDM2 gene expression and enhances p53 acetylation in MCF‐7 cells
Authors: Proietti Sara , Cucina Alessandra , Dobrowolny Gabriella , D'Anselmi Fabrizio , Dinicola Simona , Masiello Maria Grazia , Pasqualato Alessia , Palombo Alessandro , Morini Veronica , Reiter Russel J. , Bizzarri Mariano 
Published: June 2014

AbstractCompelling evidence demonstrated that melatonin increases p53 activity in cancer cells. p53 undergoes acetylation to be stabilized and activated for driving cells destined for apoptosis/growth inhibition. Over‐expression of p300 induces p53 acetylation, leading to cell growth arrest by increasing p21 expression. In turn, p53 activation is mainly regulated in the nucleus by MDM2. MDM2 also acts as E3 ubiquitin ligase, promoting the proteasome‐dependent p53 degradation. MDM2 entry into the nucleus is finely tuned by two different modulations: the ribosomal protein L11, acts by sequestering MDM2 in the cytosol, whereas the PI3K‐AkT‐dependent MDM2 phosphorylation is mandatory for MDM2 translocation across the nuclear membrane. In addition, MDM2‐dependent targeting of p53 is regulated in a nonlinear fashion by MDM2/MDMX interplay. Melatonin induces both cell growth inhibition and apoptosis in MCF7 breast cancer cells. We previously reported that this effect is associated with reduced MDM2 levels and increased p53 activity. Herein, we demonstrated that melatonin drastically down‐regulates MDM2 gene expression and inhibits MDM2 shuttling into the nucleus, given that melatonin increases L11 and inhibits Akt‐PI3K‐dependent MDM2 phosphorylation. Melatonin induces a 3‐fold increase in both MDMX and p300 levels, decreasing simultaneously Sirt1, a specific inhibitor of p300 activity. Consequently, melatonin‐treated cells display significantly higher values of both p53 and acetylated p53. Thus, a 15‐fold increase in p21 levels was observed in melatonin‐treated cancer cells. Our results provide evidence that melatonin enhances p53 acetylation by modulating the MDM2/MDMX/p300 pathway, disclosing new insights for understanding its anticancer effect.
Estimating quantitative genetic parameters in wild populations: a comparison of pedigree and genomic approaches
Authors: Bérénos Camillo , Ellis Philip A. , Pilkington Jill G. , Pemberton Josephine M. 
Published: June 2014

AbstractThe estimation of quantitative genetic parameters in wild populations is generally limited by the accuracy and completeness of the available pedigree information. Using relatedness at genomewide markers can potentially remove this limitation and lead to less biased and more precise estimates. We estimated heritability, maternal genetic effects and genetic correlations for body size traits in an unmanaged long‐term study population of Soay sheep on St Kilda using three increasingly complete and accurate estimates of relatedness: (i) Pedigree 1, using observation‐derived maternal links and microsatellite‐derived paternal links; (ii) Pedigree 2, using SNP‐derived assignment of both maternity and paternity; and (iii) whole‐genome relatedness at 37 037 autosomal SNPs. In initial analyses, heritability estimates were strikingly similar for all three methods, while standard errors were systematically lower in analyses based on Pedigree 2 and genomic relatedness. Genetic correlations were generally strong, differed little between the three estimates of relatedness and the standard errors declined only very slightly with improved relatedness information. When partitioning maternal effects into separate genetic and environmental components, maternal genetic effects found in juvenile traits increased substantially across the three relatedness estimates. Heritability declined compared to parallel models where only a maternal environment effect was fitted, suggesting that maternal genetic effects are confounded with direct genetic effects and that more accurate estimates of relatedness were better able to separate maternal genetic effects from direct genetic effects. We found that the heritability captured by SNP markers asymptoted at about half the SNPs available, suggesting that denser marker panels are not necessarily required for precise and unbiased heritability estimates. Finally, we present guidelines for the use of genomic relatedness in future quantitative genetics studies in natural populations.
Deficient sucrose synthase activity in developing wood does not specifically affect cellulose biosynthesis, but causes an overall decrease in cell wall polymers
Authors: Gerber Lorenz , Zhang Bo , Roach Melissa , Rende Umut , Gorzsás András , Kumar Manoj , Burgert Ingo , Niittylä Totte , Sundberg Björn 
Published: June 2014

Summary

The biosynthesis of wood in aspen (Populus) depends on the metabolism of sucrose, which is the main transported form of carbon from source tissues. The largest fraction of the wood biomass is cellulose, which is synthesized from UDP‐glucose. Sucrose synthase (SUS) has been proposed previously to interact directly with cellulose synthase complexes and specifically supply UDP‐glucose for cellulose biosynthesis.

To investigate the role of SUS in wood biosynthesis, we characterized transgenic lines of hybrid aspen with strongly reduced SUS activity in developing wood.

No dramatic growth phenotypes in glasshouse‐grown trees were observed, but chemical fingerprinting with pyrolysis‐GC/MS, together with micromechanical analysis, showed notable changes in chemistry and ultrastructure of the wood in the transgenic lines. Wet chemical analysis showed that the dry weight percentage composition of wood polymers was not changed significantly. However, a decrease in wood density was observed and, consequently, the content of lignin, hemicellulose and cellulose was decreased per wood volume. The decrease in density was explained by a looser structure of fibre cell walls as shown by increased wall shrinkage on drying.

The results show that SUS is not essential for cellulose biosynthesis, but plays a role in defining the total carbon incorporation to wood cell walls.
Hereditary Vitamin D–Resistant Rickets Presenting as Alopecia
Authors: Casey Genevieve , McPherson Tess , Kini Usha , Ryan Fiona , Taibjee Saleem M. , Moss Celia , Burge Susan 
Published: June 2014

AbstractHereditary vitamin D–resistant rickets (HVDRR) is a rare autosomal recessive disorder caused by mutations in the vitamin D receptor (VDR) gene. We report the case of an infant presenting with alopecia, growth failure, and gross motor developmental delay. Serum biochemistry and skeletal survey were consistent with rickets. After a poor response to standard treatment, genetic testing confirmed a c.147–2A>T novel mutation in the VDR gene consistent with HVDRR. It is important for dermatologists and pediatricians to recognize alopecia as a presenting sign of HVDRR because appropriate treatment leads to better growth and development of the child.
Tooth Enamel Hypoplasia in PHACE Syndrome
Authors: Chiu Yvonne E. , Siegel Dawn H. , Drolet Beth A. , Hodgson Brian D. 
Published: June 2014

AbstractIndividuals with PHACE syndrome (posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects, eye abnormalities, sternal cleft, and supraumbilical raphe syndrome) have reported dental abnormalities to their healthcare providers and in online forums, but dental involvement has not been comprehensively studied. A study was conducted at the third PHACE Family Conference, held in Milwaukee, Wisconsin, in July 2012. A pediatric dentist examined subjects at enrollment. Eighteen subjects were enrolled. The median age was 4.2 years (range 9 mos–9 yrs; 14 girls, 4 boys). Eleven of 18 patients had intraoral hemangiomas and five of these (50%) had hypomature enamel hypoplasia. None of the seven patients without intraoral hemangiomas had enamel hypoplasia. No other dental abnormalities were seen. Enamel hypoplasia may be a feature of PHACE syndrome when an intraoral hemangioma is present. Enamel hypoplasia increases the risk of caries, and clinicians should refer children with PHACE syndrome to a pediatric dentist by 1 year of age.
Traces of Reduction: Marion and Heidegger on the Phenomenon of Religion
Authors: Rogers Brian 
Published: June 2014

AbstractIn his work, Being Given, Jean‐Luc Marion calls for a phenomenological investigation of the givenness (donation) of the phenomenon. As a phenomenologist of religion, Marion aims to give a philosophical account of the possibility of revelation, something which by definition is unconditionally given. In Being Given, he contends that his phenomenological reduction to unconditional givenness (in the figure of the saturated phenomenon) can account for religious phenomena in a way that respects the subject matter, all the while remaining philosophically neutral. In this paper I argue that Marion's aim to maintain strict philosophical neutrality interferes with his attempt to respect the subject matter of his own investigation, i.e., the givenness of revelation, since revelation is recognizably given, even as possibility, only in the non‐neutral context of an interpretive tradition. I establish the latter claim with recourse to Heidegger's early hermeneutic sketches of ‘primordial Christian religiosity.’ In turn, I call for a phenomenological Destruktion of Marion's work in order to release its potential as a non‐neutral investigation of a distinctively Catholic religiosity.
Existential Phenomenology and the Conceptual Problem of Other Minds
Authors: Skirke Christian 
Published: June 2014

AbstractWe ordinarily think that self and other coexist as subjects with mutually exclusive mental lives. The conceptual problem of other minds challenges this common thought by raising doubts that coexistence and mutual exclusivity come together in a coherent idea of others. Existential phenomenology is usually taken to be exempt from skeptical worries of this sort because it conceives of subjects as situated or embodied, offering an inclusive account of coexistence. I submit that this well‐entrenched view faces a serious dilemma: either the ordinary distinction between self and other has to be given up, or accounts of situated and embodied coexistence presuppose a non‐phenomenological solution to (a close relative of) the conceptual problem of other minds. I then propose a way out for existential phenomenology by sketching a Sartre‐inspired phenomenological response to the problem.
Validation of the Suicide Resilience Inventory‐25 with American and Chinese College Students
Authors: Fang Qijuan , Freedenthal Stacey , Osman Augustine 
Published: June 2014

This study is the first to evaluate evidence for measurement invariance and the psychometric properties of the Suicide Resilience Inventory‐25 (SRI‐25; Osman et al., ) in college‐age samples in both the United States and China. We found strong support for full measurement invariance of the three‐factor structure of the SRI‐25 in the U.S. (113 men and 238 women) and Chinese (121 men and 205 women) samples. In addition, we found that the U.S. sample scored significantly higher than the Chinese sample on all the individual scale scores. Composite scale reliability estimates ranged from moderate (ρ = .83) to high (ρ = .93) across the groups. Although not an aim of the current study, we examined estimates of internal consistency of the SRI‐25 scales for men and women within each sample. Differential correlates of the SRI‐25 scales were explored further for each sample. These results provide support for the use of the SRI‐25 in U.S. and Chinese student samples.
More Likely to Be Poor Whatever the Measure: Working‐Age Persons with Disabilities in the United States*
Authors: Brucker Debra L. , Mitra Sophie , Chaitoo Navena , Mauro Joseph 
Published: June 2014

ObjectiveThis article examines whether disability is a correlate of poverty when poverty is measured using (1) the official poverty measure; (2) the supplemental poverty measure (SPM); and (3) two multidimensional poverty measures created by the authors.MethodsData from the Current Population Survey are used to explore the relationship between poverty and disability for each measure. Differences across disability status were tested for statistical significance.ResultsDisability is associated with poverty, irrespective of the poverty measure under use. The gap in poverty rates between persons with and without disabilities is smaller when using the SPM as compared to the official poverty measure. The gap in poverty rates between persons with and without disabilities is highest when using multidimensional poverty measures.ConclusionWorking‐age persons with disabilities are more likely to be poor whatever the measure under use. They are a disadvantaged group in the United States.
Relationships within theMelitaea phoebespecies group (Lepidoptera:Nymphalidae): new insights from molecular and morphometric information
Authors: TÓTH JÁNOS P. , BERECZKI JUDIT , VARGA ZOLTÁN , ROTA JADRANKA , SRAMKÓ GÁBOR , WAHLBERG NIKLAS 
Published: June 2014

AbstractThe genusMelitaeaconsists of about 80 species, divided into ten species groups, which are all restricted to thePalaearctic region. TheMelitaea phoebegroup was defined byHiggins based on morphological characters such as wing pattern and genital structures. According to his interpretation, theM. phoebegroup included seven species:M. phoebe,M. sibina,M. scotosia,M. aetherie,M. collina,M. consulisandM. turkmanica. The taxonomy of thephoebespecies group has been poorly resolved and recent results on the species composition within the group suggest the need for a re‐evaluation. In this study molecular sequences (5985 bp) including one mitochondrial (COI) and up to six nuclear (CAD,EF‐1α,GAPDH,MDH,RpS5andwingless) gene regions from 38 specimens of theMelitaea phoebespecies groupsensuHiggins and some closely related taxa from thePalaearctic region were analysed. The possible evolution of the processus posterior of the male genitalia was also reconstructed based on a shape mapping technique. The analysis of the combined data shows a very clear pattern and almost all relationships are highly supported. Based on the combinedBayesian tree and the shape of the processus posterior of the male genitalia, four main groups are recognised: (i)collinagroup, (ii)arduinnagroup, (iii)aetheriegroup and (iv)phoebegroup. The status ofM. ornata,M. zagrosiandM. scotosiaas species is confirmed, and the results also indicate thatM. telona(s.s.) fromIsrael is a separate species.
Variant CJD and blood transfusion: are there additional cases?
Authors: Davidson L. R. R. , Llewelyn C. A. , Mackenzie J. M. , Hewitt P. E. , Will R. G. 
Published: June 2014

Background and ObjectivesIn this study, we compare variant Creutzfeldt‐Jakob disease (vCJD) cases definitely linked to blood transfusion, those with a history of blood transfusion in which no donor has developed vCJD and primary cases with no history of blood transfusion. The aim is to determine whether there are any differences in the demographics or clinical phenotype in these groups that might suggest additional cases of transfusion transmission of vCJD.Materials and MethodsAll cases of vCJD who are old enough to donate blood (i.e. >17 years old) are notified to the UKBTS at diagnosis, regardless of whether they are known to have a blood donation history. A search is then made for donor records and, if found, all components produced and issued to hospitals are identified and their fate determined. Recipient details are then checked against the NCJDRSU register to establish whether there is a match between these individuals and patients who have been diagnosed with vCJD. In the reverse study, attempts are made to trace the donors to all cases reported to have received a blood transfusion and donors' details are checked against the register to determine if any have developed vCJD.ResultsOf the 177 cases of vCJD diagnosed in the UK as of 1 February 2014, the TMER study identified 15 cases reported to have received a blood transfusion. Transfusion records were unavailable for 4 of these cases, all pre‐1980, and in one other case there was no transfusion recorded in the medical notes. Transfusion records were found for 10 cases. One case transfused at symptom onset was excluded from this analysis. The mean age at onset of symptoms of the remaining nine transfusion recipients (four female and five male) was 42·9 years; 57·6 years in the three known transfusion‐transmitted cases and 35·5 years in the six not linked cases. In one of these cases, details of components transfused were unavailable, and the remaining five cases received a total of 116 donor exposures with 112 donors identified, none of whom is known to have developed clinical vCJD. To date, five of the 112 identified donors have died and none was certified as dying of vCJD or any other neurological disorder. Two of the transfusion‐transmitted cases did not fulfil diagnostic criteria for probable vCJD during life but were confirmed at post‐mortem. Both cases were in the older age range (68 and 74 years, respectively), and neither had a positive MRI brain scan. The remaining cases all fulfilled the criteria for the diagnosis of vCJD in life, but two of these had atypical features and were older than the expected age at onset for vCJD.ConclusionIn conclusion, it is possible that one or more of the vCJD cases that received a blood transfusion derived from an individual not known to have vCJD were infected by the blood transfusion. However, the evidence for this is weak, and the absence of a past history of transfusion in most cases of vCJD excludes a large number of unrecognised transfusion‐transmitted cases.
Persistence of Parvovirus B19 (B19V) DNA and humoral immune response in B19V‐infected blood donors
Authors: Juhl D. , Görg S. , Hennig H. 
Published: June 2014

Background and ObjectivesParvovirus B19 (B19V) DNA seems to persist in the plasma of B19V‐infected blood donors. The relevance of this for recipients of single‐donor blood components is yet unclear.Material and MethodsWe studied serial archive and follow‐up samples from 75 B19V‐infected blood donors to obtain more data about the duration and degree of viraemia and the presence of IgG and IgM anti‐B19V. IgG antibodies were further characterized by Western blot analysis in 29 donors.ResultsIn 411 B19V DNA‐positive samples collected, we found high concentrations (>106 IU B19V DNA/ml plasma) in five. B19V DNA persisted for a mean of 21·5 months (range: 2·3–52·4; 95% confidence interval, 19·1–23·9 months) in all donors. Only 15 such samples had either no or low‐titre IgG anti‐B19V. IgG antibodies were predominantly directed against epitopes on the minor capsid protein VP1, thus probably of neutralizing type with high avidity. IgM anti‐B19V was detectable in 9/13 samples with high DNA concentrations.ConclusionsThe vast majority of single‐donor blood components with detectable B19V DNA are probably not infectious for their recipients because DNA is at only low levels and the donors also have potentially neutralizing antibodies with high avidity. Anti‐B19V IgM testing does not identify every donation with high B19V DNA concentrations, but, in addition to B19V NAT testing, donors with persistent IgG anti‐B19V might be considered ‘B19V‐safe’ for single‐donor blood components.
Isotype Switching Increases Efficacy of Antibody Protection against Staphylococcal Enterotoxin B-Induced Lethal Shock and Staphylococcus aureus Sepsis in Mice
Authors: Varshney Avanish K. , Wang Xiaobo , Aguilar Jorge L. , Scharff Matthew D. , Fries Bettina C. 
Published: June 2014

ABSTRACT

Staphylococcal enterotoxin B (SEB) is a potent toxin that is produced by
Staphylococcus aureus
strains and is classified as a category B select agent. We have previously shown that monoclonal antibody (MAb) 20B1, a murine anti-SEB IgG1, successfully treats SEB-induced lethal shock (SEBILS) and bacteremia that is caused by SEB-producing
S. aureus
. In this study, we have generated two isotype switch variants of the original IgG1 MAb 20B1, an IgG2a and IgG2b, both bearing the same variable region sequence, and compared their neutralizing and protective activity in
in vitro
and
in vivo
assays, respectively. All 3 isotypes demonstrated comparable affinity to SEB and comparable 50% inhibitory concentrations (IC
50
s) in T cell proliferation assays.
In vivo
, however, the IgG2a isotype variant of 20B1 exhibited significantly greater protection than IgG1 or IgG2b in murine SEB intoxication and
S. aureus
sepsis models. Protection was associated with downmodulation of inflammatory host response. Our data demonstrate that changing the isotype of already protective MAbs, without affecting their antigen specificity or sensitivity, can result in an enhancement of their protective ability. Isotype selection, therefore, should be carefully considered in the development of toxin-neutralizing MAbs and the design of antibody therapeutics.

IMPORTANCE
The purpose of this study was to enhance the protective efficacy of an existing, protective monoclonal antibody against staphylococcal enterotoxin B. Using two
in vivo
mouse models, our study demonstrates that the protective efficacy of a monoclonal antibody may be improved by inducing an isotype switch at the Fc region of an antibody, without altering the antigen specificity or sensitivity of the antibody. The development of therapeutic MAbs with higher efficacy may allow for the achievement of equal therapeutic benefit with a lower dosage. In turn, the use of lower doses may reduce the cost of these therapies, while reducing the potential for adverse side effects.
Saccharomyces boulardii
Administration Changes Gut Microbiota and Reduces Hepatic Steatosis, Low
-
Grade Inflammation, and Fat Mass in Obese and Type 2 Diabetic
db
/
db
Mice
Authors: Everard Amandine , Matamoros Sébastien , Geurts Lucie , Delzenne Nathalie M. , Cani Patrice D. 
Published: June 2014

ABSTRACT

Growing evidence shows that gut microbes are key factors involved in the regulation of energy homeostasis, metabolic inflammation, lipid metabolism, and glucose metabolism. Therefore, gut microbiota modulations caused by selectively fermented oligosaccharides or probiotic bacteria constitute an interesting target in the physiopathology of obesity. However, to date, no probiotic yeast has been investigated in this context. Therefore, our study aimed to evaluate the impact of the most-studied probiotic yeast (i.e.,
Saccharomyces boulardii
Biocodex) on obesity and associated metabolic features, such as fat mass development, hepatic steatosis, and low-grade inflammation, in obese mice.
S. boulardii
was administered daily by oral gavage to leptin-resistant obese and type 2 diabetic mice (
db/db
) for 4 weeks. We found that
S. boulardii
-treated mice exhibited reduced body weight, fat mass, hepatic steatosis, and inflammatory tone. Interestingly, these effects of
S. boulardii
on host metabolism were associated with local effects in the intestine.
S. boulardii
increased cecum weight and cecum tissue weight but also induced dramatic changes in the gut microbial composition at the phylum, family, and genus levels. These gut microbiota changes in response to
S. boulardii
may also be correlated with the host metabolism response. In conclusion, this study demonstrates for the first time that
S. boulardii
may act as a beneficial probiotic treatment in the context of obesity and type 2 diabetes.

IMPORTANCE
To date, no probiotic yeast have been investigated in the context of obesity and type 2 diabetes. Here we found that type 2 diabetic and obese mice (
db/db
) treated with
Saccharomyces boulardii
exhibited reduced body weight, fat mass, hepatic steatosis, and inflammatory tone. These effects on host metabolism were associated with local effects in the intestine. Importantly, by using pyrosequencing, we found that
S. boulardii
treatment induces changes of the gut microbiota composition at the phylum, family, and genus levels. Moreover, we found that gut microbiota changes in response to
S. boulardii
were correlated with several host metabolism responses.