bluuebunny/crossref_metadata_2025 huggingface dataset:
The relationship between metacognitive beliefs, auditory hallucinations, and hallucination‐related distress in clinical and non‐clinical voice‐hearers
Authors: Hill Katy , Varese Filippo , Jackson Mike , Linden David E.J.
Published: May 2012

Objectives: To test the hypothesis that metacognitive beliefs are implicated in the development of distress associated with auditory verbal hallucinations (AVHs) rather than in their aetiology.

Design: A cross sectional questionnaire design was used.

Methods: Three groups of participants were recruited (n= 20 in each group); clinical voice‐hearers diagnosed with psychiatric disorders; non‐clinical voice‐hearers with no psychiatric history; and non‐clinical participants with no history of voices or psychiatric disorder. All participants were screened for psychiatric symptomatology and completed a self‐report measure of their metacognitive beliefs (MCQ‐30). In addition, the two groups of voice‐hearers were interviewed about dimensions of their voices (i.e., content, frequency, distress, and disruption).

Results: The clinical group scored significantly higher than the two non‐clinical groups on two subscales of the MCQ‐30 (negative beliefs about worry concerning controllability and danger and negative beliefs about thoughts concerning need for control). There were no significant differences between the two non‐clinical groups on MCQ‐30 scores. Regression analyses revealed that the negative beliefs about need for control subscale of the MCQ‐30 was the only significant predictor of voice‐related distress, although this effect was no longer significant after controlling for the effect of group.

Conclusions: These results are consistent with previous findings suggesting that metacognitive beliefs are not directly implicated in the aetiology of AVHs, but may be associated with psychological distress. Further research is however needed to determine whether metacognitive style may directly impact upon voice‐related distress.
Gene Therapy for Aromatic
l
-Amino Acid Decarboxylase Deficiency
Authors: Hwu Wuh-Liang , Muramatsu Shin-ichi , Tseng Sheng-Hong , Tzen Kai-Yuan , Lee Ni-Chung , Chien Yin-Hsiu , Snyder Richard O. , Byrne Barry J. , Tai Chun-Hwei , Wu Ruey-Meei
Published: May 2012

Gene therapy can restore some motor function in patients with aromatic
l
-amino acid decarboxylase deficiency.
High-Throughput Sequencing Detects Minimal Residual Disease in Acute T Lymphoblastic Leukemia
Authors: Wu David , Sherwood Anna , Fromm Jonathan R. , Winter Stuart S. , Dunsmore Kimberly P. , Loh Mignon L. , Greisman Harvey A. , Sabath Daniel E. , Wood Brent L. , Robins Harlan
Published: May 2012

High-throughput sequencing can detect minimal residual disease comparable to multiparametric flow cytometry in T-ALL patients.
Coming Unglued: The Potential to Break Apart Biofilms
Authors: Shrout Joshua D.
Published: May 2012

Norspermidine targets certain matrix molecules to promote biofilm disassembly and prevent biofilm formation.
The impact of immersion protection requirements on hair dryer electrocutions in the USA
Authors: Rodgers Gregory B , Garland Sarah
Published: May 2012

Objective

To evaluate the effectiveness of the immersion protection requirements of a voluntary safety standard for portable handheld hair dryers in preventing electrocution deaths in the USA.

Methods

The present work was an interrupted time series study design. Data on annual hair dryer-related electrocution deaths resulting from water contact were developed for the 1980–2007 study period. A multivariate Poisson regression model for rate data was used to evaluate the impact of the immersion protection requirements during the post-intervention period. The analysis controlled for the estimated number of hair dryers in use and the estimated number of US homes equipped with ground fault circuit interrupters, safety devices that would address hair dryer electrocutions even in the absence of the immersion protection requirements of the voluntary standard. The implementation of the 1987 and 1991 immersion protection requirements of the voluntary standard for portable handheld hair dryers was the intervention studied. The main outcome measure was the estimated reduction in the hair dryer electrocution rate associated with the immersion protection requirements of the voluntary standard.

Results

After controlling for covariates, the immersion protection requirements were estimated to reduce the rate of hair dryer immersion electrocution deaths by 96.6% (95% CI, 90.8% to 98.8%). This suggests the prevention of about 280 immersion electrocution deaths involving hair dryers during the post-intervention period (1987–2007).

Conclusions

The immersion protection requirements of the voluntary safety standard for hair dryers have been highly effective in reducing hair dryer electrocutions.
Physical and psychosocial factors associated with wrist or hand pain among Australian hospital-based nurses
Authors: Surawera Inoka K , Hoe Victor C W , Kelsall Helen L , Urquhart Donna M , Sim Malcolm R
Published: May 2012

Objective

To assess the personal, physical and psychosocial factors associated with wrist or hand pain in Australian hospital-based nurses.

Methods

Wrist or hand pain, associated disability and sickness absence, demographic, occupational, physical, psychosocial and personal factors among nurses working for three hospitals in Melbourne, Australia, were assessed in a cross-sectional study. Factors associated with wrist or hand pain in the past month were assessed using logistic regression.

Results

This analysis was based on 1111 participants. The prevalence of wrist or hand pain in the past month was 15.3%. Repeated movements of the wrist or finger >4 h (OR 2.63, 95% CI 1.80 to 3.84), high job strain (1.54, 1.04 to 2.28), job insecurity (1.55, 1.04 to 2.28), somatisation tendency (2.73, 1.75 to 4.26), pain catastrophising (1.56, 1.03 to 2.37), better mental (0.97, 0.95 to 0.99) and physical (0.96, 0.94-0.98) health and well-being were associated with wrist or hand pain in the past month, after adjusting for possible confounding factors. When all significant factors were examined in the same model, repeated movements of the wrist or finger >4 h (2.50, 1.71 to 3.67), somatisation (2.61, 1.65 to 4.13) and better physical health and well-being (0.96, 0.94 to 0.99) remained independently associated with wrist or hand pain in the past month.

Conclusions

This study highlights that wrist or hand pain is prevalent in hospital nurses. Workplace physical factors and personal factors were associated with wrist or hand pain. Further longitudinal investigation is needed to examine the predictive nature of these factors.
Bovine lactoferrin in preventing preterm delivery associated with sterile inflammation1This article is part of Special Issue entitled Lactoferrin and has undergone the Journal's usual peer review process.
Authors: Paesano Rosalba , Pietropaoli Miriam , Berlutti Francesca , Valenti Piera
Published: May 2012

Preterm delivery (PTD) occurs before the 37th week of gestation. Iron deficiency anemia and inflammatory processes either related to infection or sterile inflammatory response represent risk factors for PTD. Bovine lactoferrin (bLf), an emerging important regulator of iron and inflammatory homeostasis, can represent a new therapeutic approach for PTD treatment. Here an open-label cohort and subcohort study is reported. The cohort was designed to assess the effect of bLf oral administration on iron and inflammatory homeostasis in anemic pregnant women. The subcohort including women of the cohort with PTD threat was additionally treated with bLf intravaginal administration. A significant improvement of hematological parameters was observed in the women’s cohort together with a consistent decrease of serum interleukin-6 (IL-6) levels. Combined administration of oral and intravaginal bLf to the women’s subcohort with PTD threat decreased IL-6 in both serum and cervicovaginal fluids, cervicovaginal prostaglandin F2α, and suppressed uterine contractility. BLf administration blocked further shortening of cervical length and the increase of fetal fibronectin thus prolonging the length of pregnancy. The deliveries occurred between the 37th and 38th week of gestation. These results provide strong evidence for a role of bLf in PTD treatment, thus extending the therapeutic potential of this multifunctional natural protein.
Transdermal administration of lactoferrin with sophorolipid1This article is part of a Special Issue entitled Lactoferrin and has undergone the Journal's usual peer review process.
Authors: Ishii Nanase , Kobayashi Toshihiro , Matsumiya Kentaro , Ryu Mizuyuki , Hirata Yoshihiko , Matsumura Yasuki , Suzuki Yasushi A.
Published: May 2012

Lactoferrin (Lf), a multifunctional glycoprotein, is known to activate dermal fibroblasts. Enhancing percutaneous absorption without decreasing the activity of Lf is critical in making the dermal administration of Lf beneficial. Sophorolipid (SL), a glycolipid-type biosurfactant, is known to form assemblies that may elevate the efficiency of the transdermal delivery of active ingredients. Here, we investigated the role of SL in the transdermal absorption of bovine Lf (bLf) and the effect of SL on the bLf activity on dermal fibroblasts. Transdermal absorption of bLf through a model skin was enhanced by 1.3-fold to 1.7-fold when SL was added. The effects of SL on the bLf activities on dermal fibroblasts were examined by cell proliferation activities and by gene expression levels of elastic fiber components, collagen IV, and hyaluronan synthases, revealing that SL did not depress the effect of bLf to any extent. Instead, the tropoelastin gene expression was upregulated ∼60-fold by bLf alone, which was further increased to ∼160-fold by bLf and SL together, suggesting a significant synergism between bLf and SL. Protein levels of elastin, assessed by immunohistochemistry, correlated well with the results of gene expressions. These results indicate the feasibility of the transdermal administration of bLf with SL.
Effect of bovine lactoferrin on the minimum inhibitory concentrations of ampicillin and trimethoprim–sulfamethoxazole for clinical Shigella spp. strains1This article is part of a Special Issue entitled Lactoferrin and has undergone the Journal’s usual peer review process.
Authors: Mosquito Susan , Zegarra Gianina , Villanueva Claudia , Ruiz Joaquin , Ochoa Theresa J.
Published: May 2012

Here, we determined the effect of bovine lactoferrin (bLF) on the minimum inhibitory concentration (MIC) of ampicillin and trimethoprim–sulfamethoxazole in Shigella . Using a microdilution method, the MIC was determined in the presence or absence of bovine lactoferrin (10 mg/mL) on 88 Shigella strains (56 Shigella flexneri , 15 Shigella boydii , 13 Shigella sonnei , and 4 Shigella dysenteriae ) previously isolated from peruvian children <2 years old. A fold change of 2 or more in MIC values was considered significant. For ampicillin, 67 (76%) strains were highly resistant; one-third of the strains (32%) showed a decrease in ampicillin MIC in the presence of LF. This was more typical of MIC values in less resistant strains. For 7 (8%) ampicillin-resistant strains, the decrease in the MIC resulted in the strains reaching the cutoff for susceptible in the presence of bLF. For trimethoprim–sulfamethoxazole, 93% of the isolates (n = 82) were highly resistant and only 4 isolates (5%) decreased their MIC in the presence of bLF. None of the trimethoprim–sulfamethoxazole resistant strains became susceptible in the presence of LF. The decrease in the MIC in the presence of bLF seems to depend on the mechanisms of action of each antibiotic. In vivo studies are needed to further evaluate bLF as a coadjuvant to antibiotic treatment of resistant Shigella.
Bovine lactoferrin: involvement of metal saturation and carbohydrates in the inhibition of influenza virus infection1This article is part of a Special Issue entitled Lactoferrin and has undergone the Journal's usual peer review process.
Authors: Pietrantoni Agostina , Ammendolia Maria Grazia , Superti Fabiana
Published: May 2012

Influenza is a highly contagious, acute respiratory illness, which represents one of the main plagues worldwide. Even though some antiviral drugs are available, the alarming increase of virus strains resistant to them highlights the need to find new antiviral compounds. As we have recently demonstrated that bovine lactoferrin (bLf) prevents influenza virus-induced apoptosis, in the present wor,k we have attempted to investigate in depth the mechanism of the anti-influenza virus effect of this protein. To this aim, experiments have been carried out whereby different forms of bLf were added to the cells during different phases of viral infection. Results obtained showed that bLf was able to prevent influenza virus cytopathic effects when incubated with the cells after the adsorption step, independently from ion saturation or carbohydrate content. Moreover, the influence of iron saturations or sialic acid/carbohydrates removal on bLf activity on the early phases of infection has been observed. Our results provide further insights on the antiviral activity of bLf and suggest novel strategies for treatment of influenza virus infection.
Kinetic and thermodynamic parameters for heat denaturation of human recombinant lactoferrin from rice1This article is part of a Special Issue entitled Lactoferrin and has undergone the Journal's usual peer review process.
Authors: Castillo Eduardo , Pérez María Dolores , Franco Indira , Calvo Miguel , Sánchez Lourdes
Published: May 2012

Heat denaturation of recombinant human lactoferrin (rhLf) from rice with 3 different iron-saturation degrees, holo rhLf (iron-saturated), AsIs rhLf (60% iron saturation), and apo rhLf (iron-depleted), was studied. The 3 forms of rhLf were subjected to heat treatment, and the kinetic and thermodynamic parameters of the denaturation process were determined. Thermal denaturation of rhLf was assessed by measuring the loss of reactivity against specific antibodies. Dt values (time to reduce 90% of immunoreactivity) decreased with increasing temperature of treatment for apo and holo rhLf, those values being higher for the iron-saturated form, which indicates that iron confers thermal stability to rhLf. However, AsIs rhLf showed a different behaviour with an increase in resistance to heat between 79 °C and 84 °C, so that the kinetic parameters could not be calculated. The heat denaturation process for apo and holo rhLf was best described assuming a reaction order of 1.5. The activation energy of the denaturation process was 648.20 kJ/mol for holo rhLf and 406.94 kJ/mol for apo rhLf, confirming that iron-depleted rhLf is more sensitive to heat treatment than iron-saturated rhLf.
The role of lactoferrin binding protein B in mediating protection against human lactoferricin1This article is part of a Special Issue entitled Lactoferrin and has undergone the Journal's usual peer review process.
Authors: Morgenthau Ari , Livingstone Margaret , Adamiak Paul , Schryvers Anthony B.
Published: May 2012

Bacteria that inhabit the mucosal surfaces of the respiratory and genitourinary tracts of mammals encounter an iron-deficient environment because of iron sequestration by the host iron-binding proteins transferrin and lactoferrin. Lactoferrin is also present in high concentrations at sites of inflammation where the cationic, antimicrobial peptide lactoferricin is produced by proteolysis of lactoferrin. Several Gram-negative pathogens express a lactoferrin receptor that enables the bacteria to use lactoferrin as an iron source. The receptor is composed of an integral membrane protein, lactoferrin binding protein A (LbpA), and a membrane-bound lipoprotein, lactoferrin binding protein B (LbpB). LbpA is essential for growth with lactoferrin as the sole iron source, whereas the role of LbpB in iron acquisition is not yet known. In this study, we demonstrate that LbpB from 2 different species is capable of providing protection against the killing activity of a human lactoferrin-derived peptide. We investigated the prevalence of lactoferrin receptors in bacteria and examined their sequence diversity. We propose that the protection against the cationic antimicrobial human lactoferrin-derived peptide is associated with clusters of negatively charged amino acids in the C-terminal lobe of LbpB that is a common feature of this protein.
Biochemical and molecular impacts of lactoferrin on small intestinal growth and development during early life1This article is part of a Special Issue entitled Lactoferrin and has undergone the Journal's usual peer review process.
Authors: Liao Yalin , Jiang Rulan , Lönnerdal Bo
Published: May 2012

Postnatal modeling of the intestinal epithelium has long-term impacts on the healthy development of infants and relies largely on nutrient composition of the diet. Lactoferrin (Lf) is among the various human milk trophic factors that facilitate the infant intestinal adaptation. Hydrolysis of Lf is minimal at the prevailing postprandial pH of infants, and Lf may therefore have greater biological potential in infants than in adults. Lf bidirectionally stimulates concentration-dependent proliferation and differentiation of small intestinal epithelial cells, and therefore affects small intestinal mass, length, and epithelial digestive enzyme expression. A 105 kDa Lf receptor (LfR) specifically mediates the uptake of Lf into enterocytes and crypt cells. Mechanistically, the complex of Lf and LfR is internalized through clathrin-mediated endocytosis; both iron-free apo-Lf and iron-saturated holo-Lf activate the PI3K/Akt pathway, whereas only apo-Lf triggers ERK1/2 signaling. Lf enters the nucleus, where it can stimulate thymidine incorporation into crypt cells, regulating transcription of genes such as TGF-β1. In the fetus, the plasma membrane LfR is at the highest abundance in the small intestine, and the receptor gene is tightly controlled at multiple levels. Aspecific microRNA, miR-584, is involved in the posttranscriptional regulation of LfR, and in the human LfR DNA promoter, 2 Sp1 binding sites have been characterized functionally. Finally, cell proliferation and global gene expression reveal that native bovine Lf can perform biological activities similar to those exerted by human Lf in postnatal small intestinal development.
Patterns of sequence variation within the Neisseria meningitidis lactoferrin binding proteins1This article is part of a Special Issue entitled Lactoferrin and has undergone the Journal’s usual peer review process.
Authors: Adamiak Paul , Beddek Amanda J. , Pajon Rolando , Schryvers Anthony B.
Published: May 2012

Lactoferrin binding proteins A and B (LbpA and LbpB) compose the lactoferrin receptor of the obligate human pathogen Neisseria meningitidis . This receptor is thought to be important for colonization and initiation of invasive disease because of its role in acquiring host iron and providing protection from the cationic peptide, lactoferricin. By virtue of its function, the receptor is accessible to the host immune system and displays substantial sequence variation. In this study, we analyzed a broad collection of LbpAs (62) and LbpBs (101) to determine the distribution of sequence variation within each protein and to search for patterns between sequence similarity and strain typing. The sequence variation in LbpA was predominantly observed in 3 surface loops and, surprisingly, in the N-terminal region immediately upstream of the predicted TonB box. The analysis of LbpB revealed that the variability was distributed throughout the protein, particularly in the highly variable negatively charged regions in the C-lobe, but otherwise was greater in the N-lobe than the C-lobe. There was no readily identifiable correlation between the sequence variation within LbpA, LbpB, multi-locus sequence type, or serogroup.
Crystal structure of the N-lobe of lactoferrin binding protein B from Moraxella bovis1 1This paper is an invited article as a result of a presentation at the International Lactoferrin Conference held in Mazatlan, Mexico (May 2011), and has undergone the Journal’s usual peer review process.
Authors: Arutyunova Elena , Brooks Cory L. , Beddek Amanda , Mak Michelle W. , Schryvers Anthony B. , Lemieux M. Joanne
Published: May 2012

Lactoferrin (Lf) is a bi-lobed, iron-binding protein found on mucosal surfaces and at sites of inflammation. Gram-negative pathogens from the Neisseriaceae and Moraxellaceae families are capable of using Lf as a source of iron for growth through a process mediated by a bacterial surface receptor that directly binds host Lf. This receptor consists of an integral outer membrane protein, lactoferrin binding protein A (LbpA), and a surface lipoprotein, lactoferrin binding protein B (LbpB). The N-lobe of the homologous transferrin binding protein B, TbpB, has been shown to facilitate transferrin binding in the process of iron acquisition. Currently there is little known about the role of LbpB in iron acquisition or how Lf interacts with the bacterial receptor proteins. No structural information on any LbpB or domain is available. In this study, we express and purify from Escherichia coli the full-length LbpB and the N-lobe of LbpB from the bovine pathogen Moraxella bovis for crystallization trials. We demonstrate that M. bovis LbpB binds to bovine but not human Lf. We also report the crystal structure of the N-terminal lobe of LbpB from M. bovis and compare it with the published structures of TbpB to speculate on the process of Lf mediated iron acquisition.
Endocytosis and trafficking of human lactoferrin in macrophage-like human THP-1 cells1This article is part of a Special Issue entitled Lactoferrin and has undergone the Journal’s usual peer review process.
Authors: Florian Paula , Macovei Alina , Sima Livia , Nichita Norica , Mattsby-Baltzer Inger , Roseanu Anca
Published: May 2012

Different cell types have been reported to internalize lactoferrin (Lf) by specific or nonspecific receptors. Our studies focused on the endocytic pathway of human Lf in macrophage-like THP-1 cells. Lactoferrin was found to be internalized by THP-1 cells differentiated with phorbol myristate acetate. Incubation of cells with chlorpromazine and dansylcadaverine, inhibitors of clathrin-dependent endocytosis, led to a 50% inhibition of Lf internalization compared with untreated cells. Bafilomycin A1 and NH4Cl treatment also resulted in 40%–60% inhibition, respectively, suggesting that the internalization of Lf may partly be mediated by acidic endosome-like organelles. Endocytic uptake of Lf was also cholesterol-dependent, as shown by methyl-β-cyclodextrin or nystatin treatment of the cells prior to internalization. Partial colocalization of Lf and EEA-1, a marker specific for early endosomes, could be observed. Colocalization of Lf with a specific endoplasmic reticulum marker was also detected. Our results suggest that Lf is internalized mainly by the clathrin-dependent pathway in THP-1 cells and targets the ER. The physiological consequences of this intracellular trafficking will be the subject of future investigations.
Transgenic milk containing recombinant human lactoferrin modulates the intestinal flora in piglets1This article is part of a Special Issue entitled Lactoferrin and has undergone the Journal’s usual peer review process.
Authors: Hu Wenping , Zhao Jie , Wang Jianwu , Yu Tian , Wang Jing , Li Ning
Published: May 2012

Lactoferrin (LF) is a beneficial multifunctional protein in milk. The objective of this study was to determine whether bovine transgenic milk containing recombinant human lactoferrin (rhLF) can modulate intestinal flora in the neonatal pig as an animal model for the human infant. We fed 7-day-old piglets (i) ordinary whole milk (OM), (ii) a 1:1 mixture of OM and rhLF milk (MM), or (iii) rhLF milk (LFM). LFM provided better average daily mass gain than OM (P = 0.007). PCR–denaturing gradient gel electrophoresis and 16S rDNA sequencing analysis revealed that the LFM piglets exhibited more diversity of the intestinal flora than the OM group. Except for the colon in the LFM group, an increasing trend in microbial diversity occurred from the duodenum to the colon. Fecal flora was not different across different ages or different treatment groups, but a cluster analysis showed that the fecal flora of OM- and MM-fed piglets had a higher degree of similarity than that of LFM-fed piglets. Based on culture-based bacterial counts of intestinal content samples, concentrations of Salmonella spp. in the colon and of Escherichia coli throughout the intestine were reduced with LFM (P < 0.01). Concentrations of Bifidobacterium spp. in the ileum and of Lactobacillus spp. throughout the intestine were also increased with LFM (P ≤ 0.01). We suggest that rhLF can modulate the intestinal flora in piglets.
Oral lactoferrin treatment resolves amoebic intracecal infection in C3H/HeJ mice1This article is part of a Special Issue entitled Lactoferrin and has undergone the Journal’s usual peer review process.
Authors: León-Sicairos Nidia , Martínez-Pardo Leonardo , Sánchez-Hernández Beatriz , de la Garza Mireya , Carrero Julio César
Published: May 2012

Entamoeba histolytica is a protozoan parasite that causes amoebiasis, an illness that affects many people around the world. We have previously reported that lactoferrin is able to kill E. histolytica in in vitro cultures. The aim of the present study was to evaluate the therapeutic effect of orally administered bovine lactoferrin in the control of intestinal amoebiasis of susceptible C3H/HeJ mice. The results showed that 20 mg lactoferrin/kg orally administered each day for 1 week was able to eliminate the infection in 63% of the mice, since neither trophozoites nor evidence of epithelial damage and (or) swelling were found in tissue sections of the cecum. The rest of the treated animals (37%) showed a decrease in trophozoite numbers and mucus secreted to the lumen, as compared with untreated and infected mice (p < 0.05). By immunohistochemistry, the profile of secreted cytokines in the cecum revealed that infected but untreated animals showed a mixed Th1/regulatory cytokines profile, whereas the cecum of mice treated (cured) showed a Th2 cytokine profile (IL-4) and expression of the multifunctional IL-6. In addition, cytokines and increasing cecal production of total IgA antibodies were found associated with little inflammation and disease control observed in the cecum of lactoferrin-treated animals. These results suggest that oral administration of lactoferrin can control intestinal amoebic infection probably by killing amoebas or favoring their removal and reestablish the antiinflammatory intestinal environment.
Lactoferrin, a bird’s eye view
Authors: Vogel Hans J.
Published: May 2012

Lactoferrin is an abundant iron-binding protein in milk. This 80 kDa bilobal glycoprotein is also present in several other secreted bodily fluids, as well as in the secondary granules of neutrophils. The potent iron-binding properties of lactoferrin can locally create iron deficiency, and this is an important factor in host defense as it prevents bacteria from growing and forming biofilms. In addition to having antibacterial activity, lactoferrin is now known to have a long list of other beneficial biological properties. It has direct antiviral, antifungal, and even some anticancer activities. It can also promote wound healing and bone growth, or it can act as an iron carrier. Moreover, lactoferrin displays a cytokine-like “alarmin” activity, and it activates the immune system. Simultaneously, it can bind endotoxin (lipopolysaccharide), and in doing so, it modulates the activity of the host immune response. The majority of these intriguing biological activities reside in the unique positively charged N-terminal region of the protein. Interestingly, several peptides, which retain many of the beneficial activities, can be released from this region of lactoferrin. An isoform of the human protein, known as delta-lactoferrin, is expressed inside many cells, where it acts as a transcription factor. Lactoferrin purified from human and bovine milk have very similar but not completely identical properties. Lactoferrin receptors have been identified on the surface of various cells, and some of these can bind both the human and the bovine protein. Because of the extensive health-promoting effects of lactoferrin, there has been considerable interest in the use of bovine or human lactoferrin as a “protein nutraceutical” or as a therapeutic protein. When lactoferrin is used as a “biologic drug”, it seems to be orally active in contrast to most other therapeutic proteins.
Lactoferrin – 50 years on
Authors: Brock Jeremy H.
Published: May 2012

It is now some 50 years since iron-binding lactoferrin was first isolated and purified, an event that opened the way to subsequent extensive research on lactoferrin structure and function. The initial recognition that lactoferrin closely resembled the plasma iron-transport protein transferrin meant that lactoferrin was first thought to mediate intestinal iron absorption or to act as an antimicrobial agent. It was also suggested that it could mediate the hyposideraemia of inflammation. This paper will assess to what extent early proposals have stood the test of time and also suggest possible mechanisms by which lactoferrin can mediate the large number of potential functions that have subsequently been proposed. It will also review the ability of lactoferrin to resist digestion in the gastrointestinal tract and identify areas for future research.
MULTIPLE SUPERCONDUCTING GAPS, ANISOTROPIC SPIN FLUCTUATIONS AND SPIN-ORBIT COUPLING IN IRON-PNICTIDES
Authors: YANG JIE , ZHENG GUO-QING
Published: May 2012

This article reviews the NMR and NQR studies on iron-based high-temperature superconductors by the IOP/Okayama group. It was found that the electron pairs in the superconducting state are in the spin-singlet state with multiple fully-opened energy gaps. The antiferromagnetic spin fluctuations in the normal state are found to be closely correlated with the superconductivity. Also, the antiferromagnetic spin fluctuations are anisotropic in the spin space, which is different from the case in copper oxide superconductors. This anisotropy originates from the spin-orbit coupling and is an important reflection of the multiple-bands nature of this new class of superconductors.
A NOTE ON SPIN PUMPING THEORY WITH LANDAU–LIFSHITZ–GILBERT EQUATION UNDER QUANTUM FLUCTUATION; NECESSITY FOR QUANTIZATION OF LOCALIZED SPIN
Authors: NAKATA KOUKI
Published: May 2012

We would like to point out the blind spots of the approach combining the spin pumping theory proposed by Tserkovnyak et al. with the Landau–Lifshitz–Gilbert equation; this method has been widely used for interpreting vast experimental results. The essence of the spin pumping effect is the quantum fluctuation. Then, localized spin degrees of freedom should be quantized, i.e. be treated as magnons not as classical variables. Consequently, the precessing ferromagnet can be regarded as a magnon battery. This point of view will be useful for further progress of spintronics.
CATHODOLUMINESCENCE AND PHOTOLUMINESCENCE OF NV CENTERS
Authors: ROY-GUAY DAVID , PIORO-LADRIÈRE MICHEL , MORRIS DENIS , TALLAIRE ALEXANDRE , ACHARD JOCELYN , DROUIN DOMINIQUE
Published: May 2012

Nitrogen-vacancy (NV) centers in diamond are a promising candidate as a solid state qubit memory for quantum information as they possess very long coherence times even at room temperature. Furthermore, NV centers are very sensitive to their electromagnetic environment and are addressable in the GHz frequency range. Here we review our progress towards the detection of single NV centers for the implementation of fast on demand coupling between NV centers and GHz electromagnetic fields. Precisely, we present efforts towards mapping NV centers with a cathodoluminescence setup. Developing such capability is important for patterning local one-qubit gates for the application of high amplitude electromagnetic fields as a tuning parameter.
EFFICIENT ULTRAVIOLET LIGHT FREQUENCY DOWN-SHIFTING BY A THIN FILM OF ZnO NANOPARTICLES
Authors: APOSTOLUK ALEKSANDRA , MASENELLI BRUNO , TUPIN ELSA , CANUT BRUNO , HAPIUK DIMITRI , MÉLINON PATRICE , DELAUNAY JEAN-JACQUES
Published: May 2012

The maximal efficiency of a single junction solar cell (SC) is defined as the Shockley–Queisser limit, which determines the maximal output power which can be furnished by a SC as a function of the bandgap of the semiconductor constituting the cell. The short wavelength spectral response of a SC can be improved if a luminescent down-converting layer is added to the SC structure. We propose the use of a layer containing ZnO nanoparticles (NPs) as a luminescent down-shifter. ZnO is able to absorb efficiently the ultraviolet light (λ < 400 nm), where the SC spectral response is low and to re-emit lower energy photons (longer wavelength photons) for which the SC spectral response is enhanced, thus increasing the total photocurrent. The stoichiometry and crystallinity of ZnO NPs can be controlled and adjusted to obtain the highest visible photoluminescent emission, indicator of an efficient down-shifting. The ratio between the ZnO UV absorption and visible emission is also estimated and from these results we expect the increase of the SC efficiency using ZnO NPs as a down-shifting layer placed on the front side of the SC.
REDUCING THE USAGE OF CRUDE OIL — WHAT CAN BE LEARNED FROM HIGHEST CRUDE CONSUMER COUNTRIES?
Authors: GAVISH BEZALEL , GAVISH ROYI
Published: May 2012

The production and consumption of crude oil became a major issue with the sharp increase in crude oil prices that took place during the last few months. We investigate the relationship between crude oil consumption and the GDP of the top crude oil consuming countries. The amount of GDP produced per barrel of crude oil varies significantly between different countries; the ratio is in the range of 2% to 10% of the GDP when the price of a barrel of crude oil is $100. The paper attempts to explain the high variability with the aim of learning from high GDP producers as to how they are able to generate a larger GDP per barrel of crude oil consumption. The paper also identifies a hysteresis effect in crude consumption reduction and illustrates how understanding it can lead to better production and conservation policies.
A CONCEPTUAL SNAPSHOT OF THE FIRST DECADE (2002–2011) OF THE INTERNATIONAL JOURNAL OF INFORMATION TECHNOLOGY & DECISION MAKING
Authors: LÓPEZ-HERRERA A. G. , HERRERA-VIEDMA E. , COBO M. J. , MARTÍNEZ M. A. , KOU GANG , SHI YONG
Published: May 2012

In this paper, we carry out a study about the main themes treated by the International Journal of Information Technology & Decision Making during its first 10 years (2002–2011). The themes are detected, quantified and visualized using an approach that combines performance analysis and science mapping. Bibliometric maps based on co-word analysis will help us to visualize the division of the journal into several subfields and their relationships, providing interesting insight into the main topics being discussed in the journal in these years. In addition, the study will show the most productive themes (according to published papers) and the most impacting ones (according to received citations).
The effects of 13 wk of liraglutide treatment on endocrine and exocrine pancreas in male and female ZDF rats: a quantitative and qualitative analysis revealing no evidence of drug-induced pancreatitis
Authors: Vrang Niels , Jelsing Jacob , Simonsen Lotte , Jensen Andres Eskjær , Thorup Inger , Søeborg Henrik , Knudsen Lotte Bjerre
Published: May 2012

A possible association between glucagon-like peptide-1 (GLP-1) analogs and incidences of pancreatitis has been suggested based on clinical studies. In male and female diabetic Zucker diabetic fatty (ZDF) rats, we investigated the effects of continuous administration of liraglutide and exenatide on biochemical [lipase, pancreatic amylase (P-amylase)] and histopathological markers of pancreatitis. Male and female ZDF rats were dosed for 13 wk with liraglutide (0.4 or 1.0 mg·kg−1·day−1sc once daily) or exenatide (0.25 mg·kg−1·day−1sc, Alzet osmotic minipumps). P-amylase and lipase plasma activity were measured, and an extended histopathological and stereological (specific cell mass and proliferation rate) evaluation of the exocrine and the endocrine pancreas was performed. Expectedly, liraglutide and exenatide lowered blood glucose and Hb A1cin male and female ZDF rats, whereas β-cell mass and proliferation rate were increased with greatly improved blood glucose control. Whereas neither analog affected lipase activity, small increases in P-amylase activity were observed in animals treated with liraglutide and exenatide. However, concurrent or permanent increases in lipase and P-amylase activity were never observed. Triglycerides were lowered by both GLP-1 analogs. The qualitative histopathological findings did not reveal adverse effects of liraglutide. The findings were mainly minimal in severity and focal in distribution. Similarly, the quantitative stereological analyses revealed no effects of liraglutide or exenatide on overall pancreas weight or exocrine and duct cell mass or proliferation. The present study demonstrates that, in overtly diabetic male and female ZDF rats, prolonged exposure to GLP-1 receptor agonists does not affect biochemical or histopathological markers of pancreatitis, and whereas both exenatide and liraglutide increase β-cell mass, they have no effect on the exocrine pancreas. However, clinical outcome studies and studies using primate tissues and/or studies in nonhuman primates are needed to further assess human risk.
IGF-IR signaling attenuates the age-related decline of diastolic cardiac function
Authors: Moellendorf Sarah , Kessels Claudia , Peiseler Lena , Raupach Annika , Jacoby Christoph , Vogt Nora , Lindecke Antje , Koch Linda , Brüning Jens , Heger Jacqueline , Köhrer Karl , Gödecke Axel
Published: May 2012

Insulin-like growth factor (IGF-I) signaling has been implicated to play an important role in regulation of cardiac growth, hypertrophy, and contractile function and has been linked to the development of age-related congestive heart failure. Here, we address the question to what extent cardiomyocyte-specific IGF-I signaling is essential for maintenance of the structural and functional integrity of the adult murine heart. To investigate the effects of IGF-I signaling in the adult heart without confounding effects due to IGF-I overexpression or adaptation during embryonic and early postnatal development, we inactivated the IGF-I receptor (IGF-IR) by a 4-hydroxytamoxifen-inducible Cre recombinase in adult cardiac myocytes. Efficient inactivation of the IGF-IR (iCMIGF-IRKO) as assessed by Western analysis and real-time PCR went along with reduced IGF-I-dependent Akt and GSK3β phosphorylation. Functional analysis by conductance manometry and MRI revealed no functional alterations in young adult iCMIGF-IRKO mice (age 3 mo). However, when induced in aging mice (11 mo) diastolic cardiac function was depressed. To address the question whether insulin signaling might compensate for the defective IGF-IR signaling, we inactivated β-cells by streptozotocin. However, the diabetes-associated functional depression was similar in control and iCMIGF-IRKO mice. Similarly, analysis of the cardiac gene expression profile on 44K microarrays did not reveal activation of overt adaptive processes. Endogenous IGF-IR signaling is required for conservation of cardiac function of the aging heart, but not for the integrity of cardiac structure and function of young hearts.
Genetic locus on mouse chromosome 7 controls elevated heart rate
Authors: Smolock Elaine M. , Ilyushkina Irina A. , Ghazalpour Anatole , Gerloff Janice , Murashev Arkady N. , Lusis Aldons J. , Korshunov Vyacheslav A.
Published: May 2012

Elevated heart rate (HR) is a risk factor for cardiovascular diseases. The goal of the study was to map HR trait in mice using quantitative trait locus (QTL) analysis followed by genome-wide association (GWA) analysis. The first approach provides mapping power and the second increases genome resolution. QTL analyses were performed in a C3HeB×SJL backcross. HR and systolic blood pressure (SBP) were measured by the tail-cuff plethysmography. HR was ∼80 beats/min higher in SJL compared with C3HeB. There was a wide distribution of the HR (536–763 beats/min) in N2 mice. We discovered a highly significant QTL (logarithm of odds = 6.7, P < 0.001) on chromosome 7 (41 cM) for HR in the C3HeB×SJL backcross. In the Hybrid Mouse Diversity Panel (58 strains, n = 5–6/strain) we found that HR (beats/min) ranged from 546 ± 12 in C58/J to 717 ± 7 in MA/MyJ mice. SBP (mmHg) ranged from 99 ± 6 in strain I/LnJ to 151 ± 4 in strain BXA4/PgnJ. GWA analyses were done using the HMDP, which revealed a locus (64.2–65.1 Mb) on chromosome 7 that colocalized with the QTL for elevated HR found in the C3HeB×SJL backcross. The peak association was observed for 17 SNPs that are localized within three GABAA receptor genes. In summary, we used a combined genetic approach to fine map a novel elevated HR locus on mouse chromosome 7.
Prospective Study of Changes in the Metabolomic Profiles of Men during Their First Three Months of Androgen Deprivation Therapy for Prostate Cancer
Authors: Saylor Philip J. , Karoly Edward D. , Smith Matthew R.
Published: May 2012

Purpose: Androgen deprivation therapy (ADT) for prostate cancer causes an increase in fasting insulin and adverse changes in body composition and serum lipid profile. It is unknown what other metabolic alterations are caused by ADT. To better characterize the metabolic effects of ADT, we measured changes in plasma metabolomic profile at baseline and after the first 3 months of therapy.

Experimental Design: Fasting plasma samples were drawn from 36 subjects at baseline and after 3 months of gonadotropin releasing hormone (GnRH) agonist therapy. Extracted samples were split into equal parts for analysis on the gas chromatography-mass spectrometry and liquid chromatography/tandem mass spectrometry platforms.

Results: Of the 292 identified metabolites, 56 changed significantly (P < 0.05) from baseline to 3 months. Notable changes were grouped as follows: (i) Multiple steroids were lower at 3 months, consistent with the effect of therapy on gonadal androgen synthesis. (ii) Most bile acids and their metabolites were higher during treatment. Cholesterol levels changed very little. (iii) Markers of lipid beta-oxidation (acetyl-carnitines and ketone bodies) and omega-oxidation were lower at 3 months. (iv) Two previously identified biomarkers of insulin resistance (2-hydroxybutyrate and branch chain keto-acid dehydrogenase complex products) were stable to lower at 3 months.

Conclusions: Unbiased metabolomic analyses revealed expected, novel, and unexpected results. Steroid levels fell, consistent with the effects of ADT. Most bile acids and their metabolites increased during ADT, a novel finding. Biomarkers of lipid metabolism and insulin resistance fell, unexpected given that ADT has been shown to increase fasting insulin. Clin Cancer Res; 18(13); 3677–85. ©2012 AACR.
Development of a Human Monoclonal Antibody for Potential Therapy of CD27-Expressing Lymphoma and Leukemia
Authors: Vitale Laura A. , He Li-Zhen , Thomas Lawrence J. , Widger Jennifer , Weidlick Jeffrey , Crocker Andrea , O'Neill Thomas , Storey James , Glennie Martin J. , Grote Deanna M. , Ansell Stephen M. , Marsh Henry , Keler Tibor
Published: May 2012

Purpose: The TNF receptor superfamily member CD27 is best known for its important role in T-cell immunity but is also recognized as a cell-surface marker on a number of B- and T-cell malignancies. In this article, we describe a novel human monoclonal antibody (mAb) specific for CD27 with properties that suggest a potential utility against malignancies that express CD27.

Experimental Design: The fully human mAb 1F5 was generated using human Ig transgenic mice and characterized by analytical and functional assays in vitro. Severe combined immunodeficient (SCID) mice inoculated with human CD27-expressing lymphoma cells were administered 1F5 to investigate direct antitumor effects. A pilot study of 1F5 was conducted in non-human primates to assess toxicity.

Results: 1F5 binds with high affinity and specificity to human and macaque CD27 and competes with ligand binding. 1F5 activates T cells only in combination with T-cell receptor stimulation and does not induce proliferation of primary CD27-expressing tumor cells. 1F5 significantly enhanced the survival of SCID mice bearing Raji or Daudi tumors, which may be mediated through direct effector mechanisms such as antibody-dependent cellular cytotoxicity. Importantly, administration of up to 10 mg/kg of 1F5 to cynomolgus monkeys was well tolerated without evidence of significant toxicity or depletion of circulating lymphocytes.

Conclusions: Collectively, the data suggest that the human mAb 1F5, which has recently entered clinical development under the name CDX-1127, may provide direct antitumor activity against CD27-expressing lymphoma or leukemia, independent of its potential to enhance immunity through its agonistic properties. Clin Cancer Res; 18(14); 3812–21. ©2012 AACR.
Prediction of Incident Heart Failure in General Practice
Authors: Agarwal Sunil K. , Chambless Lloyd E. , Ballantyne Christie M. , Astor Brad , Bertoni Alain G. , Chang Patricia P. , Folsom Aaron R. , He Max , Hoogeveen Ron C. , Ni Hanyu , Quibrera Pedro M. , Rosamond Wayne D. , Russell Stuart D. , Shahar Eyal , Heiss Gerardo
Published: May 2012

Background—

A simple and effective heart failure (HF) risk score would facilitate the primary prevention and early diagnosis of HF in general practice. We examined the external validity of existing HF risk scores, optimized a 10-year HF risk function, and examined the incremental value of several biomarkers, including N-terminal pro-brain natriuretic peptide.

Methods and Results—

During 15.5 years (210 102 person-years of follow-up), 1487 HF events were recorded among 13 555 members of the biethnic Atherosclerosis Risk in Communities (ARIC) Study cohort. The area under curve from the Framingham-published, Framingham-recalibrated, Health ABC HF recalibrated, and ARIC risk scores were 0.610, 0.762, 0.783, and 0.797, respectively. On addition of N-terminal pro-brain natriuretic peptide, the optimism-corrected area under curve of the ARIC HF risk score increased from 0.773 (95% CI, 0.753–0.787) to 0.805 (95% CI, 0.792–0.820). Inclusion of N-terminal pro-brain natriuretic peptide improved the overall classification of recalibrated Framingham, recalibrated Health ABC, and ARIC risk scores by 18%, 12%, and 13%, respectively. In contrast, cystatin C or high-sensitivity C-reactive protein did not add toward incremental risk prediction.

Conclusions—

The ARIC HF risk score is more parsimonious yet performs slightly better than the extant risk scores in predicting 10-year risk of incident HF. The inclusion of N-terminal pro-brain natriuretic peptide markedly improves HF risk prediction. A simplified risk score restricted to a patient’s age, race, sex, and N-terminal pro-brain natriuretic peptide performs comparably to the full score (area under curve, 0.745) and is suitable for automated reporting from laboratory panels and electronic medical records.