bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering Escherichia coli to increase plasmid DNA production in high cell-density cultivations in batch mode
Authors: Borja Gheorghe M , Meza Mora Eugenio , Barrón Blanca , Gosset Guillermo , Ramírez Octavio T , Lara Alvaro R 
Published: September 2012

Abstract

Background
Plasmid DNA (pDNA) is a promising molecule for therapeutic applications. pDNA is produced by Escherichia coli in high cell-density cultivations (HCDC) using fed-batch mode. The typical limitations of such cultivations, including metabolic deviations like aerobic acetate production due to the existence of substrate gradients in large-scale bioreactors, remain as serious challenges for fast and effective pDNA production. We have previously demonstrated that the substitution of the phosphotransferase system by the over-expressed galactose permease for glucose uptake in E. coli (strain VH33) allows efficient growth, while strongly decreases acetate production. In the present work, additional genetic modifications were made to VH33 to further improve pDNA production. Several genes were deleted from strain VH33: the recA, deoR, nupG and endA genes were inactivated independently and in combination. The performance of the mutant strains was evaluated in shake flasks for the production of a 6.1 kb plasmid bearing an antigen gene against mumps. The best producer strain was cultivated in lab-scale bioreactors using 100 g/L of glucose to achieve HCDC in batch mode. For comparison, the widely used commercial strain DH5α, carrying the same plasmid, was also cultivated under the same conditions.

Results
The various mutations tested had different effects on the specific growth rate, glucose uptake rate, and pDNA yields (YP/X). The triple mutant VH33 Δ (recA deoR nupG) accumulated low amounts of acetate and resulted in the best YP/X (4.22 mg/g), whereas YP/X of strain VH33 only reached 1.16 mg/g. When cultivated at high glucose concentrations, the triple mutant strain produced 186 mg/L of pDNA, 40 g/L of biomass and only 2.2 g/L of acetate. In contrast, DH5α produced only 70 mg/L of pDNA and accumulated 9.5 g/L of acetate. Furthermore, the supercoiled fraction of the pDNA produced by the triple mutant was nearly constant throughout the cultivation.

Conclusion
The pDNA concentration obtained with the engineered strain VH33 Δ (recA deoR nupG) is, to the best of our knowledge, the highest reported for a batch cultivation, and its supercoiled fraction remained close to 80%. Strain VH33 Δ (recA deoR nupG) and its cultivation using elevated glucose concentrations represent an attractive technology for fast and efficient pDNA production and a valuable alternative to fed-batch cultivations of commercial strains.
Expression of miR-34 is lost in colon cancer which can be re-expressed by a novel agent CDF
Authors: Roy Sanchita , Levi Edi , Majumdar Adhip PN , Sarkar Fazlul H 
Published: September 2012

Abstract

Background
Colorectal Cancer (CRC) is one of the leading causes of death worldwide. Numerous cellular events, including deregulated expression of microRNAs (miRNAs), specifically the family of miR-34 consisting of miR-34a, b and c, is known to regulate the processes of growth and metastasis.

Methods
We evaluated the expression of miR-34 in formalin-fixed paraffin-embedded (FFPE) human colon cancer tissue specimens compared to normal colonic mucosa. Moreover, we also assessed the expression of miR-34 in colon cancer cell lines treated with our newly developed synthetic analogue of curcumin referred as difluorinated curcumin (CDF) compared to well known inhibitor of methyl transferase.

Results
We found that the expression of miR-34a and miR-34c was down-regulated in colon cancer specimens compared to normal colonic mucosa and the loss of expression was also consistent with data from colon cancer cell lines. This down-regulation was attributed to promoter hypermethylation, because we found that the treatment of colon cancer cells with 5-aza-2´-deoxycytidine, a methyltransferase inhibitor, markedly induced the levels of miR-34a and miR-34c expression. Likewise, CDF was very effective in the re-expression of miR-34a and miR-34c, which was consistent with inhibition of cell growth of both chemo-sensitive and chemo-resistant colon cancer cells. The re-expression of miR-34 led to a marked reduction in the expression of its target gene, Notch-1.

Conclusion
The loss of expression of miR-34 in colon cancer is in part due to promoter hypermethylation of miR-34, which can be re-expressed with our novel agent CDF, suggesting that CDF could be a novel demethylating agent for restoring the expression of miR-34 family, and thus CDF could become a newer therapeutic agent for the treatment of colon cancer.
Hyper IgM syndrome presenting as chronic suppurative lung disease
Authors: Montella Silvia , Maglione Marco , Giardino Giuliana , Di Giorgio Angela , Palamaro Loredana , Mirra Virginia , Ursini Matilde Valeria , Salerno Mariacarolina , Pignata Claudio , Caffarelli Carlo , Santamaria Francesca 
Published: September 2012

AbstractThe Hyper-immunoglobulin M syndromes (HIGM) are a heterogeneous group of genetic disorders resulting in defects of immunoglobulin class switch recombination. Affected patients show humoral immunodeficiency and high susceptibility to opportunistic infections. Elevated serum IgM levels are the hallmark of the disease, even though in few rare cases they may be in the normal range. Hyper IgM is associated with low to undetectable levels of serum IgG, IgA, and IgE. In some cases, alterations in different genes may be identified. Mutations in five genes have so far been associated to the disease, which can be inherited with an X-linked (CD40 ligand, and nuclear factor-kB essential modulator defects) or an autosomal recessive (CD40, activation-induced cytidine deaminase, and uracil-DNA glycosylase mutation) pattern.The patient herein described presented with recurrent upper and lower respiratory infections and evidence of suppurative lung disease at the conventional chest imaging. The presence of low serum IgG and IgA levels, elevated IgM levels, and a marked reduction of in vivo switched memory B cells led to a clinical and functional diagnosis of HIGM although the genetic cause was not identified.
Prospective validation of the “rhino conjunctivitis allergy‐control‐SCORE©” (RC‐ACS©)
Authors: Häfner Dietrich , Reich Kristian , Zschocke Ina , Lotzin Annett , Meyer Hanns , Kettner Jens , Narkus Annemie 
Published: September 2012

AbstractBackgroundRecently we reported the validation of the “Allergy‐Control‐SCORE© (ACS)” which assesses symptom severity as well as medication use on three dimensions lung, nose and eyes. The aim of this study was to test the validity of the score for eyes and nose.MethodsOne‐hundred‐twenty‐one consenting subjects (age 19‐65y), including 81 patients with allergic rhino‐conjunctivitis (RC) and 40 healthy controls, participated in the study. Patients rated daily nasal and eye symptoms using a 4‐point scale (none, mild, moderate, and severe) and their use of anti‐symptomatic medication. Validation criteria were pollen counts in the course of the study period. Discrimination capacity was analyzed by comparing the rhino‐conjunctivitis Allergy‐Control‐SCORE© (RC‐ACS©) values of allergic patients and healthy controls. Convergent reliability was assessed by correlating RC‐ACS© values with the global severity of allergy, the quality of life, and the allergy‐related medical consultations. Retest reliability was assessed by the correlation of the repeated measured RC‐ACS© scores during each of two consecutive weeks.ResultsConvergent reliability analysis indicated a significant correlation between RC‐Allergy‐Control‐SCORE© and global severity of allergy (r = 0.691; p < 0.0001), quality of life (r = 0.757; p < 0.0001) and allergy‐related medical consultations (r = 0.329; p = 0.0019). RC‐Allergy‐Control‐SCORE© showed a good retest reliability (r = 0.813; p < 0.001) and discriminated extremely well between allergic patients and healthy controls (Median: 3.7 range: 0; 14.1 vs. Median: 0 range: 0; 2.9; p < 0.001), with a sensitivity of 93.8% and a specificity of 92.5% at a score value of 0.786.ConclusionsThe RC‐ACS© can be considered as valid and reliable to assess the severity of rhino‐conjunctivitis severity in clinical trials and observational studies.
Dysfunctional breathing phenotype in adults with asthma ‐ incidence and risk factors
Authors: Agache Ioana , Ciobanu Cristina , Paul Gabriela , Rogozea Liliana 
Published: September 2012

AbstractBackgroundAbnormal breathing patterns may cause characteristic symptoms and impair quality of life. In a cross‐sectional survey 29% of adults treated for asthma in primary care had symptoms suggestive of dysfunctional breathing (DB), more likely to be female and younger, with no differences for severity of asthma. No clear risk factors were demonstrated for DB in asthma, nor the impact of asthma medication was evaluated. The objective of this study was to describe the DB phenotype in adults with asthma treated in a specialised asthma centre.MethodsAdult patients aged 17–65 with diagnosed asthma were screened for DB using the Nijmegen questionnaire (positive predictive score >23) and confirmed by progressive exercise testing. The following were evaluated as independent risk factors for DB in the multiple regression analysis: female sex; atopy, obesity, active smoker, moderate/severe rhinitis, psychopathology, GERD, arterial hypertension; severe asthma, asthma duration > 5 years, lack of asthma control, fixed airway obstruction, fast lung function decline, frequent exacerbator and brittle asthma phenotypes; lack of ICS, use of LABA or LTRA.Results91 adults with asthma, mean age 35.04 ±1.19 years, 47(51.65%) females were evaluated. 27 (29.67%) subjects had a positive screening score on Nijmegen questionnaire and 16(17.58%) were confirmed by progressive exercise testing as having DB. Independent risk factors for DB were psychopathology (p = 0.000002), frequent exacerbator asthma phenotype (p = 0.01) and uncontrolled asthma (p < 0.000001).ConclusionDysfunctional breathing is not infrequent in asthma patients and should be evaluated in asthma patients presenting with psychopathology, frequent severe asthma exacerbations or uncontrolled asthma. Asthma medication (ICS, LABA or LTRA) had no significant relation with dysfunctional breathing.
Kisspeptin Neurons from Mice to Men: Similarities and Differences
Authors: Goodman Robert L. , Lehman Michael N. 
Published: September 2012

AbstractThe discovery that kisspeptin was critical for normal fertility in humans ushered in a new chapter in our understanding of the control of GnRH secretion. In this paper, we will review recent data on the similarities and differences across several mammalian species in the role of kisspeptin in reproductive neuroendocrinology. In all mammals examined to date, there is strong evidence that kisspeptin plays a key role in the onset of puberty and is necessary for both tonic and surge secretion of GnRH in adults, although kisspeptin-independent systems are also apparent in these studies. Similarly, two groups of kisspeptin neurons, one in the arcuate nucleus (ARC) and the other more rostrally, have been identified in all mammals, although the latter is concentrated in a limited area in rodents and more scattered in other species. Estrogen has divergent actions on kisspeptin expression in these two regions across these species, stimulating it the latter and inhibiting expression in the former. There is also strong evidence that the rostral population participates in the GnRH surge, whereas the ARC population contributes to steroid-negative feedback. There may be species differences in the role of these two populations in puberty, with the ARC cells important in rats, sheep, and monkeys, whereas both have been implicated in mice. ARC kisspeptin neurons also appear to participate in the GnRH surge in sheep and guinea pigs, whereas the data on this possibility in rodents are contradictory. Similarly, both populations are sexually dimorphic in sheep and humans, whereas most data in rodents indicate that this occurs only in the rostral population. The functional consequences of these species differences remain to be fully elucidated but are likely to have significance for understanding normal neuroendocrine control of reproduction as well as for use of kisspeptin agonists/antagonists as a therapeutic tool.
5-hydroxymethyl furfural formation and reaction kinetics of different pekmez samples: effect of temperature and storage
Authors: Oral Rasim Alper , Dogan Mahmut , Sarioglu Kemal , Toker Ömer Said 
Published: September 2012

Abstract
Pekmez (molasses) is a traditional food commonly produced from grape and other kind of fruit juices by evaporation processes. In this study, 5-Hydroxymethylfurfural (HMF) level of various pekmez samples was investigated during storage at different temperatures. HMF content of apricot, mulberry, carob, grape, Juniperus communis pekmez changed from 133.0 ppm to 1060.5 ppm, from 88.2 to 1921.5 ppm, from 11.1 to 1153.6 ppm, from 75.5 to 2077.0 ppm, from 19.9 to 280.1 ppm throughout eight months storage period, respectively. Samples of pekmez from the Juniperus communis had the minimum k values for each temperature that means HMF formation in these samples were slower than other pekmez types. The kinetic data analysis for HMF formation during storage was performed and an Arrhenius equation was used to determine the effect of temperature on reaction kinetics of 5-HMF formation in pekmez samples. Ea values were found between 10.58–37.73 (kcal/mol). Apricot pekmez was found as the least sensitive sample to HMF formation resulted from temperature changes.
Assessing seasonality in clinical research
Authors: Cleophas Ton J. , Zwinderman Aeilko H. 
Published: September 2012

Abstract

Background: Seasonal patterns are assumed in many fields of medicine. However, biological processes are full of variations and the possibility of chance findings can often not be ruled out.

Methods: Using simulated data we assess whether autocorrelation is helpful to minimize chance findings and test to support the presence of seasonality.

Results: Autocorrelation required to cut time curves into pieces. These pieces were compared with one another using linear regression analysis. Four examples with imperfect data are given. In spite of substantial differences in the data between the first and second year of observation, and in spite of otherwise inconsistent patterns, significant positive autocorrelations were constantly demonstrated with correlation coefficients around 0.40 (SE 0.14).

Conclusions: Our data suggest that autocorrelation is helpful to support the presence of seasonality of disease, and that it does so even with imperfect data.
Degradation products of lignocellulosics in pulp mill effluents – comparison and evaluation of different gas chromatographic techniques for a comprehensive analysis
Authors: Bogolitsyna Anna , Becker Manuel , Borgards Andrea , Liebner Falk , Rosenau Thomas , Potthast Antje 
Published: September 2012

Abstract
Pulp mill effluents contain potentially valuable compounds and will gain even greater importance than today in future biorefinery scenarios as possible resources. Analysis of effluents of process streams is not straightforward because of the vast variety of substances embedded in the complex inorganic matrix of high concentration. In the present comparative investigation, different combinations of gas chromatography (GC) and derivatisation techniques were tested and critically evaluated aiming at a comprehensive description of all major compound classes (low-molecular weight and long-chain carboxylic acids, lignin fragments, carbohydrates and aldehydes). As derivatisation techniques, trimethylsilylation, (trimethylsilyl)methylation and methylation were applied. In addition, the effluents were analysed by pyrolysis-GC/mass spectrometry (MS), either directly or with simultaneous methylation. The study provides comprehensive information on the composition of effluents, the suitability of the various combinations of derivatisation and GC/MS techniques. The discrimination effects of the different approaches are compared. The comprehensive analytical approach led to a coherent balance in terms of the contribution of the major portion of organic compounds to the total organic carbon (TOC) content in pulp mill effluents.
A modified simple method for determination of serum α-tocopherol (vitamin E)
Authors: Jargar Jameel G. , Hattiwale Shaheenkousar H. , Das Swastika , Dhundasi Salim A. , Das Kusal K. 
Published: September 2012

Abstract

Background: Vitamin E is one of the important antioxidants linked to regulate various diseases, such as atherosclerosis, hypertension, and male infertility. A relatively simple and economic biochemical modified method has been developed to determine serum α-tocopherol concentration.

Methods: The current modified method is based on previous Baker and Frank method and the method of Martinek by using 2,2′-bipyridyl, ferric chloride, and xylene. The complex of ferrous ions generated in this reaction with 2,2′-bipyridyl is determined by using a plain enzyme-linked immunosorbent assay microplate (non-antibody coated) at 492 nm.

Results: The standard curve of this new modified method shows a linearity with correlation r=0.997 (concentration vs. absorbance). The absorbance of this color complex is directly proportional to the α-tocopherol concentration. The sensitivity of this new modified method has been compared and correlated with Baker and Frank method by using 15 human samples (r=0.99, p<0.0001).

Conclusions: This simple and economic method may be routinely used to analyze α-tocopherol concentration in serum.
Crystal structure of aqua-bis-(1,10-phenanthroline)- (5-norbornene-2,3-dicarboxylic acid)-cadmium(II)-hydrate, [Cd(C9H8O4)(C12H8N2)(H2O)]·(H2O), C42H40Cd2N4O12
Authors: Xin Ling-Yun , Yang Hong-Bing , Guo Han 
Published: September 2012

Abstract
C42H40Cd2N4O12, monoclinic, P21/c (no. 14), a = 9.475(1) Å, b = 10.879(1) Å, c = 18.819(2) Å, β = 101.092(1)°, V = 1903.7 Å3, Z = 2,Rgt(F) = 0.0192, wRref(F2) = 0.0498, T = 296 K.
Fatigue and fatigue-related symptoms in patients treated for different causes of hypothyroidism
Authors: Louwerens Marloes , Appelhof Bente C , Verloop Herman , Medici Marco , Peeters Robin P , Visser Theo J , Boelen Anita , Fliers Eric , Smit Johannes W A , Dekkers Olaf M 
Published: September 2012

ObjectiveResearch on determinants of well-being in patients on thyroid hormone replacement therapy is warranted, as persistent fatigue-related complaints are common in this population. In this study, we evaluated the impact of different states of hypothyroidism on fatigue and fatigue-related symptoms. Furthermore, the relationship between fatigue and the TSH receptor (TSHR)-Asp727Glu polymorphism, a common genetic variant of the TSHR, was analyzed.DesignA cross-sectional study was performed in 278 patients (140 patients treated for differentiated thyroid carcinoma (DTC) and 138 with autoimmune hypothyroidism (AIH)) genotyped for the TSHR-Asp727Glu polymorphism.MethodsThe multidimensional fatigue inventory (MFI-20) was used to assess fatigue, with higher MFI-20 scores indicating more fatigue-related complaints. MFI-20 scores were related to disease status and Asp727Glu polymorphism status.ResultsAIH patients scored significantly higher than DTC patients on all five MFI-20 subscales (P<0.001), independent of clinical and thyroid hormone parameters. The frequency of the TSHR-Glu727 allele was 7.2%. Heterozygous DTC patients had more favorable MFI-20 scores than wild-type DTC patients on four of five subscales. The modest effect of the TSHR-Asp727Glu polymorphism on fatigue was found in DTC patients only.ConclusionsAIH patients had significantly higher levels of fatigue compared with DTC patients, which could not be attributed to clinical or thyroid hormone parameters. The modest effect of the TSHR-Asp727Glu polymorphism on fatigue in DTC patients should be confirmed in other cohorts.
Unwalkable Neighborhoods, Poverty, and the Risk of Diabetes Among Recent Immigrants to Canada Compared With Long-Term Residents
Authors: Booth Gillian L. , Creatore Maria I. , Moineddin Rahim , Gozdyra Peter , Weyman Jonathan T. , Matheson Flora I. , Glazier Richard H. 
Published: September 2012

OBJECTIVE
This study was designed to examine whether residents living in neighborhoods that are less conducive to walking or other physical activities are more likely to develop diabetes and, if so, whether recent immigrants are particularly susceptible to such effects.

RESEARCH DESIGN AND METHODS
We conducted a population-based, retrospective cohort study to assess the impact of neighborhood walkability on diabetes incidence among recent immigrants (n = 214,882) relative to long-term residents (n = 1,024,380). Adults aged 30–64 years who were free of diabetes and living in Toronto, Canada, on 31 March 2005 were identified from administrative health databases and followed until 31 March 2010 for the development of diabetes, using a validated algorithm. Neighborhood characteristics, including walkability and income, were derived from the Canadian Census and other sources.

RESULTS
Neighborhood walkability was a strong predictor of diabetes incidence independent of age and area income, particularly among recent immigrants (lowest [quintile 1 {Q1}] vs. highest [quintile 5 {Q5}] walkability quintile: relative risk [RR] 1.58 [95% CI 1.42–1.75] for men; 1.67 [1.48–1.88] for women) compared with long-term residents (Q1 to Q5) 1.32 [1.26–1.38] for men; 1.24 [1.18–1.31] for women). Coexisting poverty accentuated these effects; diabetes incidence varied threefold between recent immigrants living in low-income/low walkability areas (16.2 per 1,000) and those living in high-income/high walkability areas (5.1 per 1,000).

CONCLUSIONS
Neighborhood walkability was inversely associated with the development of diabetes in our setting, particularly among recent immigrants living in low-income areas.
Prospects for Ecological Federalism
Authors: Grimaldi Giorgio 
Published: September 2012

Résumé Le fédéralisme et l’écologisme, en tant qu’idéologies, partagent l’objectif de concilier le point de vue global (fédération comme garantie pour la liberté, la démocratie, la paix, la prospérité, la justice et la protection des écosystèmes terrestres) et le point de vue local (l’autonomie de la communauté humaine et la lutte pour protéger l’environnement ainsi que le patrimoine social et culturel, etc.). Les deux offrent des idéaux universels de solidarité mondiale, souvent considérés comme des rêves irréalisables par la majorité des citoyens. Le fédéralisme et l’écologisme partagent également le fait d’être soutenus par des élites qualifiées, mais de ne pas être constamment en mesure d’engager et de mobiliser d’importantes parts des sociétés démocratiques. Certains éléments communs (culture de la limitation ou de l’auto-limitation, et de l’éco-développement ou l’éco-soutenabilité ; extension des droits et devoirs individuels et collectifs, et participation démocratique active au niveau local, régional, national et mondial, fondée sur une solide éducation civique et écologique ; évolution de la territorialité et de l’unité dans la diversité ; poursuite d’une politique de sécurité multidimensionnelle globale fondée sur un équilibre multipolaire du pouvoir à l’échelle mondiale, et sur les méthodes non-violentes et « défense défensive ») pourraient encourager un fédéralisme écologique, visant à traiter les phénomènes globaux, à retrouver, au niveau local et national, et à construire, au niveau régional et mondial, la capacité politique et démocratique de la gouvernance pour protéger et gérer les biens communs mondiaux. le fédéralisme écologique pourrait également promouvoir des conditions et des services garantissant une vie digne à la population, sur la base d’un minimum de valeurs partagées et d’intérêts publics.