bluuebunny/crossref_metadata_2025 huggingface dataset:
Low-drift giant magnetoresistive field sensor using modulation of free-layer magnetization direction
Authors: Wang G A , Arai S , Kato T , Iwata S
Published: May 2011

We report a field sensor, which senses the external field by detecting the change of frequency component in the modulated GMR output. The proposed sensor works in a closed-loop mode with negative feedback and the free-layer magnetization is modulated by an alternative field H
ac (2.3 Oe). The sensor output (V
out) is proportional to the applied external field (H
ex) in the range from −1.5 to +1.5 Oe. V
out is determined only by the feedback current, and has no direct relationship with the magnetoresistance ratio or the gains of the amplifiers. The proposed sensor exhibits a much lower temperature drift (about 1/50) compared with a typical magnetization rotation-type sensor and a further reduction in the drift can be achieved by improving the signal acquisition circuit; thus it can be used for high-precision dc field detection without any additional temperature compensation.
The effect of TiO2 nanotubes on the sintering behavior and properties of PZT ceramics
Authors: Dung Le Quang Tien , Truong Van Chuong , Do Phuong Anh
Published: May 2011

In this study, the effect of as-prepared annatase TiO
2 nanotubes on the sintering behavior and the piezoelectric properties of lead zirconate titanate (PZT) ceramics was investigated. Two types of PZT (with the use of TiO
2 nanotubes and commercial TiO
2) were prepared by a conventional oxide-mixing method. The density of samples using TiO
2 nanotubes tended to increase and the sintering temperature of these ceramics decreased. The electromechanical coupling factor (k

p
) of PZT ceramics was improved significantly by the use of TiO
2 nanotubes.
Recollements from generalized tilting
Authors: Yang Dong
Published: May 2011

Let

A

\mathcal {A}

be a small dg category over a field

k
k

and let

U

\mathcal {U}

be a small full subcategory of the derived category

D

A

\mathcal {D}\mathcal {A}

which generates all free dg

A

\mathcal {A}

-modules. Let

(

B

,
X
)

(\mathcal {B},X)

be a standard lift of

U

\mathcal {U}

. We show that there is a recollement such that its middle term is

D

B

\mathcal {D}\mathcal {B}

, its right term is

D

A

\mathcal {D}\mathcal {A}

, and the three functors on its right side are constructed from

X
X

. This applies to the pair

(
A
,
T
)

(A,T)

, where

A
A

is a

k
k

-algebra and

T
T

is a good

n
n

-tilting module, and we obtain a result of Bazzoni–Mantese–Tonolo. This also applies to the pair

(

A

,

U

)

(\mathcal {A}, \mathcal {U})

, where

A

\mathcal {A}

is an augmented dg category and

U

\mathcal {U}

is the category of ‘simple’ modules; e.g.,

A

\mathcal {A}

is a finite-dimensional algebra or the Kontsevich–Soibelman

A
∞

A_\infty

-category associated to a quiver with potential.
Reduced Mad2 expression keeps relaxed kinetochores from arresting budding yeast in mitosis
Authors: Barnhart Erin L. , Dorer Russell K. , Murray Andrew W. , Schuyler Scott C.
Published: May 2011

Chromosome segregation depends on the spindle checkpoint, which delays anaphase until all chromosomes have bound microtubules and have been placed under tension. The Mad1–Mad2 complex is an essential component of the checkpoint. We studied the consequences of removing one copy of MAD2 in diploid cells of the budding yeast, Saccharomyces cerevisiae. Compared to MAD2/MAD2 cells, MAD2/mad2Δ heterozygotes show increased chromosome loss and have different responses to two insults that activate the spindle checkpoint: MAD2/mad2Δ cells respond normally to antimicrotubule drugs but cannot respond to chromosomes that lack tension between sister chromatids. In MAD2/mad2Δ cells with normal sister chromatid cohesion, removing one copy of MAD1 restores the checkpoint and returns chromosome loss to wild-type levels. We conclude that cells need the normal Mad2:Mad1 ratio to respond to chromosomes that are not under tension.
The phospholipase A2enzyme complex PAFAH Ib mediates endosomal membrane tubule formation and trafficking
Authors: Bechler Marie E. , Doody Anne M. , Ha Kevin D. , Judson Bret L. , Chen Ina , Brown William J.
Published: May 2011

Previous studies have shown that membrane tubule–mediated export from endosomal compartments requires a cytoplasmic phospholipase A2(PLA2) activity. Here we report that the cytoplasmic PLA2enzyme complex platelet-activating factor acetylhydrolase (PAFAH) Ib, which consists of α1, α2, and LIS1 subunits, regulates the distribution and function of endosomes. The catalytic subunits α1 and α2 are located on early-sorting endosomes and the central endocytic recycling compartment (ERC) and their overexpression, but not overexpression of their catalytically inactive counterparts, induced endosome membrane tubules. In addition, overexpression α1 and α2 altered normal endocytic trafficking; transferrin was recycled back to the plasma membrane directly from peripheral early-sorting endosomes instead of making an intermediate stop in the ERC. Consistent with these results, small interfering RNA–mediated knockdown of α1 and α2 significantly inhibited the formation of endosome membrane tubules and delayed the recycling of transferrin. In addition, the results agree with previous reports that PAFAH Ib α1 and α2 expression levels affect the distribution of endosomes within the cell through interactions with the dynein regulator LIS1. These studies show that PAFAH Ib regulates endocytic membrane trafficking through novel mechanisms involving both PLA2activity and LIS1-dependent dynein function.
FusionMap: detecting fusion genes from next-generation sequencing data at base-pair resolution
Authors: Ge Huanying , Liu Kejun , Juan Todd , Fang Fang , Newman Matthew , Hoeck Wolfgang
Published: May 2011

Motivation: Next generation sequencing technology generates high-throughput data, which allows us to detect fusion genes at both transcript and genomic levels. To detect fusion genes, the current bioinformatics tools heavily rely on paired-end approaches and overlook the importance of reads that span fusion junctions. Thus there is a need to develop an efficient aligner to detect fusion events by accurate mapping of these junction-spanning single reads, particularly when the read gets longer with the improvement in sequencing technology.

Results: We present a novel method, FusionMap, which aligns fusion reads directly to the genome without prior knowledge of potential fusion regions. FusionMap can detect fusion events in both single- and paired-end datasets from either RNA-Seq or gDNA-Seq studies and characterize fusion junctions at base-pair resolution. We showed that FusionMap achieved high sensitivity and specificity in fusion detection on two simulated RNA-Seq datasets, which contained 75 nt paired-end reads. FusionMap achieved substantially higher sensitivity and specificity than the paired-end approach when the inner distance between read pairs was small. Using FusionMap to characterize fusion genes in K562 chronic myeloid leukemia cell line, we further demonstrated its accuracy in fusion detection in both single-end RNA-Seq and gDNA-Seq datasets. These combined results show that FusionMap provides an accurate and systematic solution to detecting fusion events through junction-spanning reads.

Availability: FusionMap includes reference indexing, read filtering, fusion alignment and reporting in one package. The software is free for noncommercial use at (http://www.omicsoft.com/fusionmap).

Contact:  ge@amgen.com

Supplementary information:  Supplementary data are available at Bioinformatics online.
Pathophysiology of neuropathic pain
Authors: Urch Catherine E.
Published: May 2011

Noxious stimuli are coded and transmitted via A and C primary afferent neurons in the periphery to the dorsal horn of the spinal cord

In the dorsal horn, transmission of noxious stimuli involves the neurotransmitters glutamate and substance P, but input can be inhibited or amplified by other influences...
Cancer neuropathic pain
Authors: Murtagh Fliss E. , Higginson Irene J.
Published: May 2011

Around a third of cancer pains may have a neuropathic component and mixed pathology is more usual than pure neuropathic pain

Compression and infiltration of nerves by tumour are the most common causes

Treatment-induced damage (chemotherapy-induced neuropathy, radiation plexitis, surgical trauma) and paraneoplastic syndromes are less common causes...
Patient perspectives
Authors: Closs S. Jos
Published: May 2011

The impact of neuropathic pain on quality of life has been under-researched and poorly understood though survey and focus group research is helping to gain better insights into what patients suffer

Neuropathic pain can result in significant sleep disturbance, fatigue, and low mood (that sometimes leads to suicidal ideation), and side-effects from drug treatment are common...
Treatment of acute coronary syndrome: Part 1: Non-ST-segment acute coronary syndrome
Authors: Trost Jeffrey C. , Lange Richard A.
Published: May 2011

Objective:

Acute coronary syndrome is a common cause of morbidity and mortality, both in the United States and worldwide. The goal of this review is to familiarize clinicians with recent information regarding the diagnosis and treatment of acute coronary syndrome.

Data Sources:

PubMed search and review of the relevant medical literature.

Acute coronary syndrome encompasses three clinical diagnoses: unstable angina, non-ST-segment elevation myocardial infarction), and ST-segment elevation myocardial infarction. The definition, pathophysiology, clinical presentation, diagnosis, and treatment of unstable angina/non-ST-segment elevation myocardial infarction are reviewed here. Diagnosing unstable angina/non-ST-segment elevation myocardial infarction is a significant challenge in critically ill patients not initially suspected of having acute coronary syndrome (i.e., noncardiac intensive care unit patients), and diagnostic and treatment strategies for these patients have not been clearly established.

Conclusions:

Patients with acute coronary syndrome benefit from intensive medical therapy, including antianginal, antiplatelet, antithrombotic, and statin agents. Depending on their risk for future cardiovascular events as well as their risk of bleeding complications, patients may benefit from either an early invasive treatment strategy, in which routine coronary revascularization is performed, or a conservative strategy, in which revascularization is reserved for patients with recurrent or provocable cardiac ischemia.
Body Composition Changes in Preterm Infants Following Hospital Discharge
Authors: Ramel Sara E. , Gray Heather L. , Ode Katie L. , Younge Noelle , Georgieff Michael K. , Demerath Ellen W.
Published: May 2011

Background and Objectives:

Infants experiencing catch‐up growth devote a greater proportion of their energy to fat deposition, potentially at the expense of gains in lean body mass. The objective of the present study was to compare the body composition of preterm and term infants after hospital discharge and to determine the effect of gestational age (GA), birth size, nutrition, and illness on growth in fat‐free mass (FFM) after hospitalization.

Patients and Methods:

Anthropometric measurements and body composition testing via air displacement plethysmography were performed on 26 appropriate‐for‐gestational‐age (AGA) preterm (mean GA 31.5 ± 2.7 weeks) and 97 AGA term (mean GA 39.8 ± 1.0 weeks) infants at term corrected age (CA) and at 3 to 4 months CA.

Results:

At term CA, preterm infants had lower FFM (3.0 vs 3.3 kg, P = 0.001), higher percentage of body fat (18.7% vs 15.2%, P < 0.0001), lower weight (P = 0.04), and shorter length (P = 0.001) than term infants. By 3 to 4 months CA, weight, length, percentage of body fat, and FFM were similar in the 2 groups. GA, inpatient nutrition, and illness were associated with FFM at 4 months CA in the preterm infants (P < 0.05).

Conclusions:

Markedly lower FFM and higher adiposity were observed in preterm infants at term CA, but these differences had lessened and were no longer statistically significant at 3 to 4 months CA. Although early nutrition was associated with growth trajectories in the hospital, the continuing influence of early illness on postdischarge growth suggests that nonnutritional factors (eg, disturbances in the growth hormone axis) also may affect body composition trajectories of preterm infants.
Emergent multicellular life cycles in filamentous bacteria owing to density-dependent population dynamics
Authors: Rossetti Valentina , Filippini Manuela , Svercel Miroslav , Barbour A. D. , Bagheri Homayoun C.
Published: May 2011

Filamentous bacteria are the oldest and simplest known multicellular life forms. By using computer simulations and experiments that address cell division in a filamentous context, we investigate some of the ecological factors that can lead to the emergence of a multicellular life cycle in filamentous life forms. The model predicts that if cell division and death rates are dependent on the density of cells in a population, a predictable cycle between short and long filament lengths is produced. During exponential growth, there will be a predominance of multicellular filaments, while at carrying capacity, the population converges to a predominance of short filaments and single cells. Model predictions are experimentally tested and confirmed in cultures of heterotrophic and phototrophic bacterial species. Furthermore, by developing a formulation of generation time in bacterial populations, it is shown that changes in generation time can alter length distributions. The theory predicts that given the same population growth curve and fitness, species with longer generation times have longer filaments during comparable population growth phases. Characterization of the environmental dependence of morphological properties such as length, and the number of cells per filament, helps in understanding the pre-existing conditions for the evolution of developmental cycles in simple multicellular organisms. Moreover, the theoretical prediction that strains with the same fitness can exhibit different lengths at comparable growth phases has important implications. It demonstrates that differences in fitness attributed to morphology are not the sole explanation for the evolution of life cycles dominated by multicellularity.
Tibrogargan and Coastal Plains rhabdoviruses: genomic characterization, evolution of novel genes and seroprevalence in Australian livestock
Authors: Gubala Aneta , Davis Steven , Weir Richard , Melville Lorna , Cowled Chris , Boyle David
Published: May 2011

Tibrogargan virus (TIBV) and Coastal Plains virus (CPV) were isolated from cattle in Australia and TIBV has also been isolated from the biting midge Culicoides brevitarsis. Complete genomic sequencing revealed that the viruses share a novel genome structure within the family Rhabdoviridae, each virus containing two additional putative genes between the matrix protein (M) and glycoprotein (G) genes and one between the G and viral RNA polymerase (L) genes. The predicted novel protein products are highly diverged at the sequence level but demonstrate clear conservation of secondary structure elements, suggesting conservation of biological functions. Phylogenetic analyses showed that TIBV and CPV form an independent group within the ‘dimarhabdovirus supergroup’. Although no disease has been observed in association with these viruses, antibodies were detected at high prevalence in cattle and buffalo in northern Australia, indicating the need for disease monitoring and further study of this distinctive group of viruses.
A mechanistic basis for potent, glycoprotein B-directed gammaherpesvirus neutralization
Authors: Glauser Daniel L. , Kratz Anne-Sophie , Gillet Laurent , Stevenson Philip G.
Published: May 2011

Glycoprotein B (gB) is a conserved, essential component of gammaherpes virions and so potentially vulnerable to neutralization. However, few good gB-specific neutralizing antibodies have been identified. Here, we show that murid herpesvirus 4 is strongly neutralized by mAbs that recognize an epitope close to one of the gB fusion loops. Antibody binding did not stop gB interacting with its cellular ligands or initiating its fusion-associated conformation change, but did stop gB resolving stably to its post-fusion form, and so blocked membrane fusion to leave virions stranded in late endosomes. The conservation of gB makes this mechanism a possible general route to gammaherpesvirus neutralization.
Specific amino acids of Olive mild mosaic virus coat protein are involved in transmission by Olpidium brassicae
Authors: Varanda Carla , Félix Maria do Rosário , Soares Cláudio M. , Oliveira Solange , Clara Maria Ivone
Published: May 2011

Transmission of Olive mild mosaic virus (OMMV) is facilitated by Olpidium brassicae (Wor.) Dang. An OMMV mutant (OMMVL11) containing two changes in the coat protein (CP), asparagine to tyrosine at position 189 and alanine to threonine at position 216, has been shown not to be Olpidium brassicae-transmissible owing to inefficient attachment of virions to zoospores. In this study, these amino acid changes were separately introduced into the OMMV genome through site-directed mutagenesis, and the asparagine-to-tyrosine change was shown to be largely responsible for the loss of transmission. Analysis of the structure of OMMV CP by comparative modelling approaches showed that this change is located in the interior of the virus particle and the alanine-to-threonine change is exposed on the surface. The asparagine-to-tyrosine change may indirectly affect attachment via changes in the conformation of viral CP subunits, altering the receptor binding site and thus preventing binding to the fungal zoospore.
Structural requirements of virion-associated cholesterol for infectivity, buoyant density and apolipoprotein association of hepatitis C virus
Authors: Yamamoto Mami , Aizaki Hideki , Fukasawa Masayoshi , Teraoka Tohru , Miyamura Tatsuo , Wakita Takaji , Suzuki Tetsuro
Published: May 2011

Our earlier study has demonstrated that hepatitis C virus (HCV)-associated cholesterol plays a key role in virus infectivity. In this study, the structural requirement of sterols for infectivity, buoyant density and apolipoprotein association of HCV was investigated further. We removed cholesterol from virions with methyl β-cyclodextrin, followed by replenishment with 10 exogenous cholesterol analogues. Among the sterols tested, dihydrocholesterol and coprostanol maintained the buoyant density of HCV and its infectivity, and 7-dehydrocholesterol restored the physical appearance of HCV, but suppressed its infectivity. Other sterol variants with a 3β-hydroxyl group or with an aliphatic side chain did not restore density or infectivity. We also provide evidence that virion-associated cholesterol contributes to the interaction between HCV particles and apolipoprotein E. The molecular basis for the effects of different sterols on HCV infectivity is discussed.
Ethylene and 1-Methylcyclopropene Differentially Regulate Gene Expression during Onion Sprout Suppression
Authors: Cools Katherine , Chope Gemma A. , Hammond John P. , Thompson Andrew J. , Terry Leon A.
Published: May 2011

Onion (Allium cepa) is regarded as a nonclimacteric vegetable. In onions, however, ethylene can suppress sprouting while the ethylene-binding inhibitor 1-methylcyclopropene (1-MCP) can also suppress sprout growth; yet, it is unknown how ethylene and 1-MCP elicit the same response. In this study, onions were treated with 10 μL L−1 ethylene or 1 μL L−1 1-MCP individually or in combination for 24 h at 20°C before or after curing (6 weeks) at 20°C or 28°C and then stored at 1°C. Following curing, a subset of these same onions was stored separately under continuous air or ethylene (10 μL L−1) at 1°C. Onions treated with ethylene and 1-MCP in combination after curing for 24 h had reduced sprout growth as compared with the control 25 weeks after harvest. Sprout growth following storage beyond 25 weeks was only reduced through continuous ethylene treatment. This observation was supported by a higher proportion of down-regulated genes characterized as being involved in photosynthesis, measured using a newly developed onion microarray. Physiological and biochemical data suggested that ethylene was being perceived in the presence of 1-MCP, since sprout growth was reduced in onions treated with 1-MCP and ethylene applied in combination but not when applied individually. A cluster of probes representing transcripts up-regulated by 1-MCP alone but down-regulated by ethylene alone or in the presence of 1-MCP support this suggestion. Ethylene and 1-MCP both down-regulated a probe tentatively annotated as an ethylene receptor as well as ethylene-insensitive 3, suggesting that both treatments down-regulate the perception and signaling events of ethylene.
Immunohistochemical findings of sebaceous carcinoma and sebaceoma: Retrieval of cytokeratin expression by a panel of anti‐cytokeratin monoclonal antibodies
Authors: ANSAI Shin‐ichi , ARASE Seiji , KAWANA Seiji , KIMURA Tetsunori
Published: May 2011

This study examined immunohistochemical findings of sebaceous carcinoma and sebaceoma. An immunohistochemical study using 13 anti‐cytokeratin (CK) antibodies (anti‐CK1, 5–8, 10 and 14–20) and 35 cases of sebaceous carcinoma (16 cases on ocular and 19 cases on extraocular regions) and 10 cases of sebaceoma (no cases arose on the eyelids) was performed. Overall, those in ocular lesions were almost the same as those for extraocular lesions in sebaceous carcinoma other than CK8. The findings in sebaceous carcinoma were almost equal to those of sebaceoma. Over 75% of cases with sebaceous carcinoma were positive with anti‐CK5 and anti‐CK14 antibodies and negative with anti‐CK1, CK10, CK15, CK17, CK18 and CK20 antibodies. Most cases (50–75%) of those were positive with CK7 and negative with CK6, CK16, CK19 and CK8. The sensitivity and specificity of immunohistochemical detection of sebaceous carcinoma using the panel of anti‐cytokeratin antibodies were lower than those of other antibodies. Immunohistochemical detection of cytokeratins in diagnosing sebaceous carcinoma should be considered to be ancillary to conventional microscopic findings and those of other antibodies.
The role of indoleamine 2, 3-dioxygenase in lepromatous leprosy immunosuppression
Authors: de Souza Sales J , Lara F A , Amadeu T P , de Oliveira Fulco T , da Costa Nery J A , Sampaio E P , Pinheiro R O , Sarno E N
Published: May 2011

To elucidate further the possible role of the tryptophan, rate-limiting enzyme indoleamine 2, 3-dioxygenase (IDO) in leprosy, the distribution of IDO-positive cells and IDO activity in the skin biopsies and sera of these patients representing the entire spectrum of the disease were studied. An increased number of macrophages/dendritic cells (DC–lineage IDO+ cells were found in lepromatous (LL) compared to tuberculoid (BT) and reversal reaction (RR) patients. IDO-positive cells showing CD68 and CD86 surface markers predominated in LL lesions, while higher levels of IDO activity were observed in the sera of LL versus BT patients. Tests revealed an increased IDO message in Mycobacterium leprae-stimulated peripheral blood mononuclear cells (PBMC) by real-time polymerase chain reaction (PCR) and increased IDO expression in M. leprae-stimulated CD14+ cells of both healthy controls (HC) and LL patients, as evaluated via flow cytometry. Increased M. leprae-induced IDO–protein synthesis was also confirmed by Western blot. Based on our in vitro studies, it was confirmed that M. leprae up-regulated IDO expression and activity in HC and LL monocytes. Interferon (IFN)-γ synergized with M. leprae in promoting IDO expression and activity in monocytes. IDO expression induced by both IFN-γ and M. leprae was abrogated by 1-methyltryptophan (1-MT). Our data suggest that M. leprae chronic infection activates the suppressive molecule IDO which, in turn, contributes to the specific immunosuppression observed in LL leprosy.
Association of functional GITR gene polymorphisms related to expression of glucocorticoid-induced tumour necrosis factor-receptor (GITR) molecules with prognosis of autoimmune thyroid disease
Authors: Tomizawa R , Watanabe M , Inoue N , Takemura K , Hidaka Y , Akamizu T , Hayakawa K , Iwatani Y
Published: May 2011

The glucocorticoid-induced tumour necrosis factor (TNF)-receptor (GITR) affects the functions of regulatory T (Treg) and effector T (Teff) cells, but the significance of this phenomenon is still unclear. To examine the association of single nucleotide polymorphisms (SNPs) in the GITR gene with the expression of GITR molecules on T cells and with the pathological conditions in patients with autoimmune thyroid disease (AITD), we examined the frequencies of four candidate SNPs in AITD patients and healthy volunteers by restriction enzyme analysis and direct sequence analyses. We also analysed the GITR expression on peripheral Treg and Teff cells in AITD patients by three-colour flow cytometry. The CC genotype in the rs3753348 C/G SNP was significantly more frequent in patients with mild Hashimoto's disease (HD) than in those with severe HD [P = 0·0117, odds ratio (OR) = 3·13]. The AA genotype in the rs2298213 A/G SNP was significantly more frequent in patients with mild HD than in patients with severe HD (P = 0·010, OR = 4·43). All patients and healthy individuals had the GG genotype in rs60038293 A/G and rs11466696 A/G SNPs. The proportions of GITR+ cells in Treg and Teff cells were significantly higher in AITD patients with the CC genotype of the rs3753348 SNP than in those with the GG genotype (P = 0·004 and P = 0·011, respectively). In conclusion, the rs3753348 C/G SNP in the GITR is associated with HD prognosis and expression on Treg and Teff cells.
α-Fetoprotein impairs activation of natural killer cells by inhibiting the function of dendritic cells
Authors: Yamamoto M , Tatsumi T , Miyagi T , Tsunematsu H , Aketa H , Hosui A , Kanto T , Hiramatsu N , Hayashi N , Takehara T
Published: May 2011

α-Fetoprotein (AFP) is a tumour-associated antigen in hepatocellular carcinoma (HCC). The biological properties of AFP have been identified in its regulatory effects on immune responses of T cells and B cells. However, AFP effects on natural killer (NK) cells are still unclear. In this study, we examined the immunoregulation of AFP on NK activity. The cytolytic activity against K562 cells and Huh7 cells of NK cells co-cultured with AFP-treated dendritic cells (DCs) (AFP-DCs) was lower than that with albumin-treated DCs (Alb-DCs). Direct addition of AFP to NK cells did not alter the cytolytic activity of NK cells. Adding AFP inhibited the interleukin (IL)-12 production of DCs after stimulation with lipopolysaccharide (LPS) [Toll-like receptor (TLR)-4 ligand], or Poly(I:C) (TLR-3 ligand), but not IL-18 production. The mRNAs of IL-12p35 and IL-12p40 were significantly inhibited in AFP-DCs compared with Alb-DCs, but those of TLR-4 or TLR-3 were not. Transwell experiments revealed that soluble factors derived from DCs played roles in inhibition of the ability of activating NK cells by AFP-DCs. Adding the neutralizing antibody of IL-12 to NK cells co-cultured with Alb-DCs resulted in a decrease of cytolytic activity to the levels of NK cells co-cultured with AFP-DCs. Adding IL-12 to NK cells co-cultured with AFP-DCs resulted in an increase of cytolytic activity to the levels of NK cells co-cultured with Alb-DCs. These demonstrated that the impairment of IL-12 production from AFP-DCs resulted in inhibition of the ability of the activation of NK cells by DCs, and thus suggests a role of AFP in HCC development.
DDAVP responsiveness in children with mild or moderate haemophilia A correlates with age, endogenous FVIII:C level and with haemophilic genotype
Authors: SEARY M. E. , FELDMAN D. , CARCAO M. D.
Published: May 2011

Summary.  In most individuals with moderate/mild haemophilia A, FVIII:C levels increase following DDAVP administration to a haemostatic range, thus avoiding the need for FVIII concentrates. We sought to determine the relationship between responsiveness to DDAVP in boys (<18 years old) with mild/moderate haemophilia and patient age, haemophilic severity and haemophilic genotype. Our cohort consisted of 13 boys with moderate and 61 boys with mild haemophilia who, between them, had 38 different mutations; 21 had unique mutations not shared by any other clinic patient, whereas 53 shared one of 17 mutations with some other clinic patient (included 26 boys with ≥1 haemophilic brother). Patient age and endogenous FVIII:C levels were strong predictors of response to DDAVP. Younger patients responded less well to DDAVP and 10 of the 11 patients, when retested at an older age, showed an improved response to DDAVP. Only 1 patient with moderate haemophilia responded to DDAVP, whereas 80% of patients with mild haemophilia responded (including all patients with an endogenous FVIII:C of >0.15 U mL−1). Almost all patients with the same mutation had the same response to DDAVP or only a minor discordance in response. Patient’s age, disease severity and genotype all are predictors of response to DDAVP.
Cardiac risk scores in high‐risk Hispanics and the predictive value of BNP
Authors: Macabasco‐O’Connell Aurelia , Danwalder Sara , Sinha Karabi
Published: May 2011

Aims.  The purpose of this study was to calculate cardiac risk scores in Hispanic subjects and to determine the predictive value of adding B‐type natriuretic peptide in identifying those with asymptomatic left ventricular dysfunction as a measure of cardiovascular disease.

Background.  Hispanics have higher rates of cardiovascular risk factors leading to coronary heart disease, asymptomatic left ventricular dysfunction and cardiovascular events. Assessing cardiac risk in these groups is important to identify those at high risk for future cardiovascular events. The use of biomarkers such as B‐type natriuretic peptide may increase the accuracy of risk prediction.

Design.  This study used a descriptive, cross‐sectional study design to determine the utility of the standard risk assessment tools (Adult Treatment Panel III and the Framingham Risk Scores risk calculator) and the B‐type natriuretic peptide biomarker to estimate coronary heart disease risk in low‐income, Hispanic participants.

Methods.  A sample of 71 patients (age 52 SD 11, 69% female) with multiple cardiovascular risk factors seen at an ambulatory clinic at a county facility was enrolled in the study. Sociodemographic and medical history information were obtained. Two widely used risk calculators (Adult Treatment Panel III and Framingham Risk Scores) were used to estimate 10‐year coronary heart disease risk in each subject. Baseline B‐type natriuretic peptide measurement and echocardiography were performed with each subject to evaluate presence of asymptomatic left ventricular dysfunction. Receiver operating curve analyses were performed to compare predictability, sensitivity and specificity of the traditional risk scores against the B‐type natriuretic peptide level to detect asymptomatic left ventricular dysfunction.

Results.  Overall mean risk scores were 5% (SD 5%) (Adult Treatment Panel III) and 10% (SD 7%) (Framingham Risk Scores). Mean B‐type natriuretic peptide levels were 108·5 (SD 191·5) pg/ml. Echocardiogram results revealed a high proportion of subjects with asymptomatic left ventricular dysfunction (74·6%). The receiver operating curves showed an area under the curve of 0·67 for B‐type natriuretic peptide (p < 0·05), 0·64 (p = NS) for Adult Treatment Panel III and 0·56 (p = NS) for Framingham Risk Scores, evidence that B‐type natriuretic peptide does significantly better than Adult Treatment Panel or Framingham Risk Scores in predicting asymptomatic left ventricular dysfunction.

Conclusion.  The inclusion of B‐type natriuretic peptide with traditional risk scores may be helpful in predicting risk and asymptomatic left ventricular dysfunction in high‐risk Hispanics.

Relevance to clinical practice.  Cardiac risk scores can assist clinicians in identifying patients at high risk for developing coronary heart disease.
Depression is associated with poor functioning in activities of daily living among nursing home residents without cognitive impairment
Authors: Drageset Jorunn , Eide Geir E , Ranhoff Anette H
Published: May 2011

Aim.  To explore depressive symptoms among nursing home residents without cognitive impairment and the relationship between their depressive symptoms and dependence on activities of daily living, comorbidity and sociodemographic variables.

Background.  Depression has become a major health care concern among older people, but depression and its association with functioning in activities of daily living among nursing home residents without cognitive impairment has previously not been studied in Norway.

Design.  A cross‐sectional comparative design.

Methods.  The sample comprised older residents (age 65–102 years; n = 227) from 30 nursing homes with at least six months of residence. All nursing home residents had a Clinical Dementia Rating scale score ≤0·5 and were capable of conversation. Scores on the Geriatric Depression Scale (15 items) and demographic variables were collected during face‐to‐face interviews. The activities of daily living were assessed using the Katz Index based on nurses’ observation, and medical diagnoses were obtained from the patient records. Pearson’s chi‐square test and ordinal logistic regression were used to identify possible associations between activities of daily living and depression.

Results.  After adjustment for age, sex, marital status, length of stay per year and education, more dependence on activities of daily living was associated with depression [odds ratio (OR): 1·18; 95% confidence interval (CI): 1·04–1·37; p = 0·02]. Higher age was associated with less depression (OR: 0·64; 95% CI: 0·43–0·94; p = 0·02), that is, the odds of depression declined by 36% for each 10‐year increase in age.

Conclusions.  Our results suggest that depression symptoms are a major health problem among nursing home residents without cognitive impairment and that younger residents are more prone to having depressive symptoms.

Relevance to clinical practice.  Nursing home staff should communicate with and observe residents closely for signs of depression, especially younger residents with high dependence on activities of daily living. In addition, formal screening of all residents for depression using an instrument that is sensitive to older people is recommended.
Nursing experience and preference for intuition in decision making
Authors: Pretz Jean E , Folse Victoria N
Published: May 2011

Aims and objectives.  This article examines the relationship between domain‐specific and domain‐general intuition among practicing nurses and student nurses to determine the role of intuition in nurses’ decision making.

Background.  Measures of nursing intuition have not been compared with one another or to measures of general preference for intuition in the psychological literature. Prior research has shown that experienced nurses rely on intuition in clinical judgement, but the various aspects of intuition associated with experience have not been fully explored.

Design.  A correlational design was used to examine the factor structures and interrelationships of self‐reported measures of intuition, as well as their relationship to experience.

Method.  A web‐based survey was given to 175 practicing nurses and student nurses in the fall of 2007 using measures of intuition from the nursing and psychological literatures. Quantitative analyses employed descriptive and inferential statistics.

Results.  Measures of preference for intuition were combined, resulting in the identification of two independent aspects of nursing intuition uniquely related to general intuition and nursing experience. Results revealed that preference for intuition in nursing was not solely due to general preference for intuition and that use of nursing intuition increased with experience.

Conclusion.  These results strengthen the knowledge base of decision making in clinical practice by examining differences in preference for use of intuition among nurses. Further interdisciplinary collaboration is recommended.

Relevance to clinical practice.  Understanding the use of intuition in clinical judgement will promote professional practice and favourable patient outcomes. If experience simply leads to increased self‐confidence and preference for the use of intuition, this may not actually be related to accuracy in judgement. However, if experience provides valuable information on associations between patient symptoms and outcomes, then the use of intuition in clinical practice should be encouraged.
Testing for causality in covarying traits: genes and latitude in a molecular world
Authors: O’BRIEN CONOR , BRADSHAW WILLIAM E. , HOLZAPFEL CHRISTINA M.
Published: May 2011

Many traits are assumed to have a causal (necessary) relationship with one another because of their common covariation with a physiological, ecological or geographical factor. Herein, we demonstrate a straightforward test for inferring causality using residuals from regression of the traits with the common factor. We illustrate this test using the covariation with latitude of a proxy for the circadian clock and a proxy for the photoperiodic timer in Drosophila and salmon. A negative result of this test means that further discussion of the adaptive significance of a causal connection between the covarying traits is unwarranted. A positive result of this test provides a point of departure that can then be used as a platform from which to determine experimentally the underlying functional connections and only then to discuss their adaptive significance.
Clinical and Molecular Characteristics of Immunodysregulation, Polyendocrinopathy, Enteropathy, X‐Linked Syndrome in China
Authors: An Y.‐F. , Xu F. , Wang M. , Zhang Z.‐Y. , Zhao X.‐D.
Published: May 2011

Immunodysregulation, polyendocrinopathy, enteropathy, X‐linked (IPEX) syndrome is a rare X‐linked recessive disorder causing life‐threatening systemic autoimmunity because of immunodysregulation. The FOXP3 gene had been reported as the responsible gene, which was critical for the functions of CD4+CD25+FOXP3+ regulatory T cells (Tregs) and maintenance of peripheral immunologic tolerance. So far, no IPEX patients with definite mutations in the FOXP3 gene had been reported in China. In this study, the genotypes and phenotypes were investigated in three IPEX infants from three unrelated Chinese families. Patient 1 (P1) presented with a classical clinical phenotype, whose mutation was a novel frameshift insertion in exon 11, led to the complete abrogation of Tregs. Patient 2 (P2) showed incomplete IPEX phenotype. He carried a missense mutation in exon 11 with slightly increased frequency of Tregs, whereas Patient 3 (P3) presented with a relatively mild classical phenotype and had a previously reported missense mutation in exon 10 with decreased frequency of Tregs. We firstly report three Chinese IPEX patients with definite mutations of FOXP3 gene. Our study indicated the potential correlation between the genotype and the phenotype of IPEX, which was different from the previous reports.
Ex vivo Expansion of CD56+ NK and NKT‐like Lymphocytes from Peripheral Blood Mononuclear Cells of Patients with Ovarian Neoplasia
Authors: Alves P. C. M. , De Angelo Andrade L. A. L. , Petta C. A. , Lorand‐Metze I. , Derchain S. F. , Guimarães F.
Published: May 2011

Methods for ex vivo expansion of natural killer (NK) cells have allowed obtaining enough numbers of human NK cells for clinical trials. However, the evaluation of these methods has been mostly limited to haematological malignancies. This study aimed at evaluating a method for selective expansion of NK cells when applied in peripheral blood mononuclear cells (PBMC) of patients with ovarian neoplasia. PBMC from 13 volunteer patients with ovarian neoplasia, seven benign and six malignant tumours, were cultured in CellGro medium supplemented with anti‐CD3 (9–10 initial days), IL‐2 and foetal bovine serum for 21 days. The resulting effector cells were evaluated for their phenotype, cytotoxicity and cytokine secretion. PBMC cultures resulted in multiple populations (NK, NKT and T) of effector cells, enriched with CD56+ lymphocytes. NK cells from patients with benign and malignant ovarian neoplasia were expanded 139.6 ± 63.4 and 82.7 ± 25.3‐fold, respectively, being the largest lymphocyte subtype among CD56+ population. Effector cells expanded from patients with malignant ovarian neoplasia had higher proportion of T lymphocytes and altered cytokine production patterns, characterized by lower INF‐γ, TNF‐α and higher IL‐4, compared with patients with benign ovarian neoplasia. Effector cells were cytotoxic against K562 and OVCAR3 cell lines. Cytotoxicity was significantly higher (P < 0.05) using magnetically separated CD56+ effector cell fractions compared with CD56‐deprived ones. The present study demonstrates the feasibility of the culture system employed to generate effector cells, enriched with CD56+ lymphocytes, from PBMC of patients with ovarian neoplasia. NK cells were the largest lymphocyte subtype among the CD56+ population and the main variable among the final effector cell preparation affecting target cell killing.
Evaluation of the Microbicidal Activity and Cytokines/Chemokines Profile Released by Neutrophils from HTLV‐1‐Infected Individuals
Authors: Bezerra Caroline A. , Cardoso Thiago M. , Giudice Angela , Porto Aurélia F. , Santos Silvane B. , Carvalho Edgar M. , Bacellar Olívia
Published: May 2011

Human T cell lymphotropic virus type‐1 (HTLV‐1) induces activation and spontaneous proliferation of T cells with production of type‐1 pro‐inflammatory cytokines. It modifies the immune response to other antigens and increases susceptibility to infectious diseases. However, little is known about innate immunity in HTLV‐1 infection. HTLV‐1‐infected individuals have higher spontaneous neutrophil activation than HTLV‐1‐seronegative individuals, as shown by the nitroblue tetrazolium (NBT) assay. This study was conducted to evaluate neutrophil function in HTLV‐1‐infected individuals. Participants in the study included 18 HTLV‐1‐infected individuals and 14 HTLV‐1‐seronegative controls. We evaluated the ability of neutrophils (PMNs) to control a parasite infection, to produce peroxynitrite, cytokines and chemokines and to express activation markers in cultures when stimulated with LPS or infected with Leishmania. When compared with the control group, there was no difference in the percentage of PMNs infected with Leishmania or in the number of amastigotes/100 PMNs in HTLV‐1‐infected individuals. The microbicidal activity of the PMNs and the levels of CXCL8 and CCL4 released by these cells did not show a difference between HTLV‐1‐infected individuals and the control group. In both the HTLV‐1 group and the control group, infection with Leishmania or stimulation of PMNs led to cellular activation. These observations suggest that neutrophils from HTLV‐1‐infected individuals have preserved their ability to become activated and to produce chemokines and peroxynitrite after stimulation and that the susceptibility to infection by intracellular Leishmania amazonensis in HTLV‐1‐infected individuals does not depend on impairment of neutrophil function.
Using spontaneous photon emission to image lipid oxidation patterns in plant tissues
Authors: Birtic Simona , Ksas Brigitte , Genty Bernard , Mueller Martin J. , Triantaphylidès Christian , Havaux Michel
Published: May 2011

Plants, like almost all living organisms, spontaneously emit photons of visible light. We used a highly sensitive, low‐noise cooled charge coupled device camera to image spontaneous photon emission (autoluminescence) of plants. Oxidative stress and wounding induced a long‐lasting enhancement of plant autoluminescence, the origin of which is investigated here. This long‐lived phenomenon can be distinguished from the short‐lived chlorophyll luminescence resulting from charge recombinations within the photosystems by pre‐adapting the plant to darkness for about 2 h. Lipids in solvent were found to emit a persistent luminescence after oxidation in vitro, which exhibited the same time and temperature dependence as plant autoluminescence. Other biological molecules, such as DNA or proteins, either did not produce measurable light upon oxidation or they did produce a chemiluminescence that decayed rapidly, which excludes their significant contribution to the in vivo light emission signal. Selective manipulation of the lipid oxidation levels in Arabidopsis mutants affected in lipid hydroperoxide metabolism revealed a causal link between leaf autoluminescence and lipid oxidation. Addition of chlorophyll to oxidized lipids enhanced light emission. Both oxidized lipids and plants predominantly emit light at wavelengths higher than 600 nm; the emission spectrum of plant autoluminescence was shifted towards even higher wavelengths, a phenomenon ascribable to chlorophyll molecules acting as luminescence enhancers in vivo. Taken together, the presented results show that spontaneous photon emission imaged in plants mainly emanates from oxidized lipids. Imaging of this signal thus provides a simple and sensitive non‐invasive method to selectively visualize and map patterns of lipid oxidation in plants.
Massively parallel sequencing and identification of genes for primary lymphoedema: a perfect fit
Authors: Ostergaard P , Simpson MA , Jeffery S
Published: May 2011

Ostergaard P, Simpson MA, Jeffery S. Massively parallel sequencing and the identification of genes for primary lymphoedema: a perfect fit.

Primary lymphoedema is a clinically and genetically heterogeneous group of disorders characterized by disruption of the lymphatic system. To date, the majority of the causative genes in primary lymphoedema have been identified through linkage analysis in large families with multiple affected subjects. Studies aimed at isolating additional genes responsible for primary lymphoedema have been hampered by cohorts comprised primarily of sporadic cases and small affected kindreds. In the absence of genetic heterogeneity, recent development of massively parallel DNA sequencing technology, specifically exome sequencing, has provided novel paradigms for disease gene identification in such cohorts. In this review, we summarize the novel approaches to disease gene discovery with massively parallel sequencing also known as Next Generation Sequencing (NGS), and show how the selection of unrelated affected cases from clinically homogenous phenotypic subclassifications is proving to be a successful approach for disease gene discovery in primary lymphoedema.