bluuebunny/crossref_metadata_2025 huggingface dataset:
Blogs, genes and immigration: Online media and minimal politics
Authors: Macgilchrist Felicitas , Böhmig Inse
Published: January 2012

This article explores the contribution of the concept of ‘minimal politics’ to understanding contemporary blogging. Politics is often used to refer only to state actions or to very rare ruptures to existing formations; citizens’ and social media are often only considered successful if they influence political leaders or lead to radical social change. The perspective adopted in this article, drawing on theories of agonistic democracy and hegemony, foregrounds the apparently quotidian ways in which current formations are destabilized. To explore the smallest radically democratic practices of contesting what appears to be a current hegemonic formation, the article analyses blog coverage of the publication in Germany of Thilo Sarrazin’s book Deutschland schafft sich ab. The book, celebrated by some sections of the media and population, argued that the genetic transmission of intelligence and the high number of Muslim immigrants in Germany was leading to the demise of the country. Analysis identified three strategies utilized by blogs to contest the Sarrazin case: rebutting, reflecting, re-articulating. The political aspect of blogging, it is argued, should not be reduced to moments of rupture or moments of consensus, but also encompass the practices of tearing apparently tiny fissures in current media/social constellations.
Phospholipidosis in Rats Treated with Amiodarone: Serum Biochemistry and Whole Genome Micro-Array Analysis Supporting the Lipid Traffic Jam Hypothesis and the Subsequent Rise of the Biomarker BMP
Authors: Mesens Natalie , Desmidt Miek , Verheyen Geert R. , Starckx Sofie , Damsch Siegrid , Vries Ronald De , Verhemeldonck Marc , Gompel Jacky Van , Lampo Ann , Lammens Lieve
Published: January 2012

To provide mechanistic insight in the induction of phospholipidosis and the appearance of the proposed biomarker di-docosahexaenoyl (C22:6)-bis(monoacylglycerol) phosphate (BMP), rats were treated with 150 mg/kg amiodarone for 12 consecutive days and analyzed at three different time points (day 4, 9, and 12). Biochemical analysis of the serum revealed a significant increase in cholesterol and phospholipids at the three time points. Bio-analysis on the serum and urine detected a time-dependent increase in BMP, as high as 10-fold compared to vehicle-treated animals on day 12. Paralleling these increases, micro-array analysis on the liver of treated rats identified cholesterol biosynthesis and glycerophospholipid metabolism as highly modulated pathways. This modulation indicates that during phospholipidosis-induction interactions take place between the cationic amphiphilic drug and phospholipids at the level of BMP-rich internal membranes of endosomes, impeding cholesterol sorting and leading to an accumulation of internal membranes, converting into multilamellar bodies. This process shows analogy to Niemann-Pick disease type C (NPC). Whereas the NPC-induced lipid traffic jam is situated at the cholesterol sorting proteins NPC1 and NPC2, the amiodarone-induced traffic jam is thought to be located at the BMP level, demonstrating its role in the mechanism of phospholipidosis-induction and its significance for use as a biomarker.
In vivo quantification of striatal dopamine D2 receptor occupancy by JNJ-37822681 using [11C]raclopride and positron emission tomography
Authors: te Beek Erik T , de Boer Peter , Moerland Matthijs , Schmidt Mark E , Hoetjes Nikie J , Windhorst Albert D , van Berckel Bart NM , Cohen Adam F , van Gerven Joop MA , Lammertsma Adriaan A
Published: January 2012

JNJ-37822681 is a novel, fast-dissociating dopamine D2 receptor antagonist, currently in development as an antipsychotic drug candidate. A previous first-in-human study demonstrated mild central nervous system effects of JNJ-37822681 in healthy male volunteers. Significant but transient serum prolactin elevations were demonstrated, whereas other neurophysiological effects were relatively small. To investigate striatal dopamine D2 receptor occupancy by variable single doses of JNJ-37822681, an open-label [11C]raclopride positron emission tomography study was performed in 12 healthy male volunteers, using the simplified reference tissue model with cerebellum as reference tissue. Oral administration of JNJ-37822681 resulted in dose-dependent dopamine D2 receptor occupancy. Receptor occupancy increased from 9–19% at 2 mg doses to 60–74% at 20 mg doses of JNJ-37822681. Therefore, single oral doses of JNJ-37822681 can produce occupancy levels that are generally associated with clinical efficacy for registered antipsychotic drugs.
The sciences of subjectivity
Authors: Shapin Steven
Published: January 2012

In historical and ethnographic studies of the making of scientific knowledge, there has been a long-standing fascination with deflating certain stories about objectivity. Among the resources used to achieve that deflation have been the notions of subjectivity, which has been treated more as a trouble for objectivity than as a knowledge-making mode open to systematic study. I describe notions of subjectivity implicated in that inattention; I trace potentially constructive links between contemporary science studies and resources in 18th-century philosophical aesthetics; I draw notice to available engagements with the mode of subjectivity known as taste, and, especially, gustation and olfaction; and I suggest ways in which we might study the achievement of intersubjectivity in these domains.
Influence of memantine on nociceptive responses of the trigeminocervical complex after formalin injection
Authors: Park Jeong Wook , Suh Gyoung Im , Shin Hae Eun , Park Go Eun
Published: January 2012

Background: Glutamate receptors are implicated in central nervous system (CNS) pain pathways, including trigeminovascular activation, central sensitization, and cortical spreading depression.

Methods: We investigated the influence of the N-methyl-d-aspartate (NMDA) receptor antagonist memantine on pain pathways involving trigeminocervical complex (TCC) using a formalin injection model. In Sprague Dawley rats, formalin was delivered into the left periorbital area. Memantine (10 mg/kg) or vehicle was injected intraperitoneally 30 min before the formalin injection. The sensory threshold for mechanical stimulation, assessed by the von Frey monofilament threshold (VFMF), was measured 1 h and 2 h after formalin injection. Formalin-induced pain behavior was measured by monitoring the time spent rubbing the injected area during 60 min after formalin injection. The brainstem was then removed, and sections that spanned the TCC were cut, and stained with a Fos antibody.

Results: Pretreatment with memantine significantly attenuated formalin-induced pain behavior (p < 0.01) and the sensory threshold for VFMF (p < 0.001). In the TCC, the increase in formalin-induced Fos immunoreactivity was significantly attenuated in the memantine group (p < 0.01).

Conclusion: The present study demonstrated that the NMDA receptor antagonist memantine inhibits the nociceptive process from trigemino-ophthalmic nerve endings to the TCC.
Maternal smoking during pregnancy and primary headache in school-aged children: a cohort study
Authors: Fabbri Carlos E , Barbieri Marco A , Silva Antônio M , Gutierrez Manoel R , Bettiol Heloisa , Speciali José G , Rona Roberto J
Published: January 2012

Background: It is not known whether smoking by mothers during pregnancy is associated with headache in their offspring.

Methods: Two prospective cohorts of 869 children aged 10–11 years from Ribeirão Preto (RP) and 805 children aged 7–9 years from São Luís (SL) were studied. Data on maternal smoking were collected at birth. Primary headache was defined as a reporting of ≥2 episodes of headache in the past 2 weeks, without any associated organic symptoms.

Results: Prevalence of headache was 28.1% in RP and 13.1% in SL as reported by the mothers and 17.5% in RP and 29.4% in SL as reported by the children. Agreement between mothers’ report and children’s self-report of primary headache in the child was poor. After adjustment, children whose mothers smoked ≥10 cigarettes per day during pregnancy presented higher prevalence of primary headache than their counterparts in both cohorts, as reported by the mother and in RP as reported by the children.

Conclusions: Maternal smoking during pregnancy was associated with headache in 7- to 11-year-olds. With one exception, the consistency of the results, despite poor agreement between maternal and children reports of headache, indicates that maternal smoking during pregnancy may contribute to headaches in their children.
Hyperintense vessels on flair imaging in reversible cerebral vasoconstriction syndrome
Authors: Chen Shih-Pin , Fuh Jong-Ling , Lirng Jiing-Feng , Wang Shuu-Jiun
Published: January 2012

Objectives: To study the frequency and significance of distal hyperintense vessels (HVs) on fluid-attenuated inversion recovery (FLAIR) imaging in patients with reversible cerebral vasoconstriction syndrome (RCVS).

Methods: Patients with RCVS were recruited during 2002 through 2009. Prominence and location of HVs on FLAIR images during the acute and recovery stages were documented. Clinical profiles, vasoconstriction scores, mean flow velocities of the middle cerebral artery (VMCA) and posterior cerebral artery (VPCA), and the Lindegaard index (LI) were collected for analysis.

Results: Ninety-five patients with RCVS (11M/84F, mean age 47.8 ± 10.9 years) were recruited. Twenty-one (22.1%) had FLAIR HVs, which were noted at a mean of 14.3 ± 12.7 days and resolved by 44.9 ± 18.8 days. Compared with patients without HVs, patients with this finding had higher vasoconstriction scores for all arterial segments; higher VMCA (121.0 ± 39.5 cm/s vs. 93.3 ± 27.8, p = 0.002), VPCA (73.3 ± 35.0 vs. 50.5 ± 17.8 cm/s, p = 0.010), and LI (2.8 ± 1.2 vs. 1.9 ± 0.5, p = 0.018), and complications such as posterior reversible encephalopathy syndrome (PRES) [8/21 (38%) vs. 0/74 (0%), p < 0.001] or ischemic stroke [5/21 (24%) vs. 1/74 (1%), p = 0.002].

Conclusions: HVs in patients with RCVS might be attributed to the failure of cerebrospinal fluid (CSF) signal nulling on FLAIR imaging due to severe cerebral hemodynamic derangements and were associated with more frequent ischemic complications.
Primary Ciliary Dyskinesia and Hydrocephalus With Aqueductal Stenosis
Authors: Vieira José Pedro , Lopes Patricia , Silva Rita
Published: January 2012

We report a female patient with situs inversus, dextrocardia, a complex heart malformation, hydrocephalus due to aqueductal stenosis, and abnormal ultrastructure of the respiratory epithelium cilia. Several animal models of this disorder implicate abnormal ciliary function in the genesis of hydrocephalus, and 11 patients were previously reported with hydrocephalus and the syndrome of primary ciliary dyskinesia. Primary ciliary dyskinesia–associated aqueductal stenosis should be considered as a possible cause for fetal or neonatal hydrocephalus if heterotaxy, heart malformations, and/or a probable genetic etiology are present.
Risk Factors for Autistic Regression
Authors: Zhang Ying , Xu Qiong , Liu Jing , Li She-chang , Xu Xiu
Published: January 2012

A subgroup of children diagnosed with autism experience developmental regression featured by a loss of previously acquired abilities. The pathogeny of autistic regression is unknown, although many risk factors likely exist. To better characterize autistic regression and investigate the association between autistic regression and potential influencing factors in Chinese autistic children, we conducted an ambispective study with a cohort of 170 autistic subjects. Analyses by multiple logistic regression showed significant correlations between autistic regression and febrile seizures (OR = 3.53, 95% CI = 1.17-10.65, P = .025), as well as with a family history of neuropsychiatric disorders (OR = 3.62, 95% CI = 1.35-9.71, P = .011). This study suggests that febrile seizures and family history of neuropsychiatric disorders are correlated with autistic regression.
3p Interstitial Deletion
Authors: Ţuţulan-Cuniţă Andreea Cristina , Papuc Sorina Mihaela , Arghir Aurora , Rötzer Katharina Magdalena , Deshpande Charulata , Lungeanu Agripina , Budişteanu Magdalena
Published: January 2012

3p interstitial deletions have emerged in recent years as a new cause of neurodevelopmental delay and intellectual disability. Since the first report of this condition in 1979, 16 cases have been described in the literature, delineating it as a presumptive syndrome. Here, we add a novel case presenting severely delayed neurodevelopment and psychomotor development; facial dysmorphism (square facies, broad forehead, short palpebral fissures, epicanthic folds, broad nasal bridge, and low-set malformed ears); cerebral, cardiac, and genital malformations; hand and feet anomalies; sacral sinus; and hearing impairment. Genetic investigations revealed a del(3)(p12.3p14.1) of 12.5 Mb, including 31 ORFs, among which ROBO2, PDZRN3, MITF, and FOXP1 are known to act in neurodevelopment. The clinical features of our patient are compared with those previously reported in the literature, thus providing further support for the delineation of the 3p interstitial deletion syndrome.
Bilateral Mental Nerve Neuropathy in an Adolescent During Sickle Cell Crises
Authors: Hamdoun Elwaseila , Davis Lamar , McCrary Sara Jane , Eklund Neva Penton , Evans Owen B.
Published: January 2012

Mental nerve neuropathy causes the “numb chin” syndrome and is usually associated with mandibular bone injury or disease in adults. It has been reported in adults during sickle cell crises. We describe a 15-year-old boy who developed bilateral mental nerve neuropathies during a sickle cell crisis. This case is unusual because of the simultaneous bilateral involvement and because of the age.
An Interdisciplinary Fetal/Neonatal Neurology Program
Authors: Scher Mark S.
Published: January 2012

A fetal/neonatal neurology program should encompass interdisciplinary service, educational and research objectives, merging curricula concerning maternal, placental, fetal and neonatal contributions to brain health and disease. This approach is anchored by research in early life programming that demonstrates that prenatal and postnatal factors influence long-term neurologic health. This concept also supports the design of neuroprotective interventions during critical periods of brain development when brain circuitries more optimally adapt to maturational challenges. Preventive, rescue and repair protocols will transform pediatric medical practices, to promote improved childhood outcomes. Inclusion of life-course science and research will identify medical and socioeconomic factors that favorably or adversely affect quality of life into adulthood. Greater awareness of the convergence of developmental origins of brain health and disease and developmental aging theories will influence public health policies, to encourage financial support for programs that will improve the quality of life for the child and adult.
Life Role Salience Dimensions and Mental Health Outcomes Among Female Expatriate Spouses in Turkey
Authors: Bikos Lynette H. , Kocheleva Julia
Published: January 2012

Using life role salience theory, we investigated the extent to which occupational, parental, marital, and home care roles explained mental health outcomes among female expatriate spouses. Participants ( N = 86) were from English-speaking Northern American or Western European countries; the average age was 38. Results of a two-way within-subject analysis of variance suggested that the occupational role was least important. In a comparison of role expectations, participants had greater value for (than commitment to) their parental role; the reverse was true for the marital role. Results of a path analysis explained 10% of the variance in psychological distress via a direct path from career role importance (β = .14) and an indirect path from the marital role importance through marital satisfaction (β = −.12). Three paths (parental role importance, β = .14; home care role importance, β = .15; indirectly from marital role importance through marital satisfaction, β = .18) explained 24% of the variance in psychological well-being.
Self-Control and Aggression
Authors: Denson Thomas F. , DeWall C. Nathan , Finkel Eli J.
Published: January 2012

Psychological science has largely neglected the role of self-control in studying aggression. Fortunately, the past half decade has witnessed a surge of research on this long-neglected topic, including two self-control-informed integrative theories of aggression. Robust experimental evidence demonstrates that self-control failures frequently predict aggression and, conversely, that bolstering self-control decreases aggression. Research on rumination also suggests that maladaptive anger regulation decreases self-control and, consequently, increases aggression. Advances from social-affective and cognitive neuroscience suggest that the neural mechanisms involved in emotion regulation and cognitive control mediate the relationship between deficient self-control and aggression.
Identifying and Remediating Failures of Selective Attention in Older Drivers
Authors: Pollatsek Alexander , Romoser Matthew R. E. , Fisher Donald L.
Published: January 2012

Older drivers are primarily overinvolved in crashes at intersections, and failure to attend to regions that contain relevant information about potential hazards is a major contributor to this problem. Corroborating this, we have found that older drivers in both controlled scenarios on a driving simulator and somewhat less controlled situations on the road attend to (i.e., fixate) target regions in intersections significantly less frequently than do younger experienced drivers. Moreover, we have developed a training program that substantially improves older drivers’ attention to these regions. Together, these findings indicate that older drivers’ less frequent scanning of regions at intersections from which hazards may emerge may be due to their developing something like an unsafe habit rather than to deteriorating physical or mental capabilities and thus that training may be effective in reducing crashes.
Calling and Career Outcome Expectations
Authors: Domene José F.
Published: January 2012

Links between young adults’ sense of calling, career outcome expectations, and self-efficacy were examined in a sample of 855 undergraduate students from three universities in Atlantic Canada. Hierarchical multiple regression revealed that participants’ presence of and search for calling accounted for a small, but significant, portion of the variance in career outcome expectations. Mediation analysis, conducted separately for each subdimension of calling, revealed that self-efficacy partially mediated the relation between purposeful work and outcome expectations, and fully mediated the relation for the calling dimensions of search for purposeful work, presence of transcendent summons, and presence of a prosocial orientation. The pattern of findings suggests that the relation between sense of calling and expectations for a successful future occupational outcome is predominantly indirect, working through influencing students’ occupational self-efficacy.
Application of the Liapunov–Floquet transformation to differential equations with time delay and periodic coefficients
Authors: Bobrenkov Oleg A , Butcher Eric A , Mann Brian P
Published: January 2012

In this paper, the Liapunov–Floquet transformation (LFT) is applied to a time-periodic delay differential equation (DDE) discretized by the Chebyshev spectral continuous time approximation. The proposed combined approach allows for the stability and time-response analysis of a constant non-delayed analog of the original periodic DDE by applying the LFT to an equivalent large-order system of time-periodic ordinary differential equations. The implementation issues are analyzed for the time-delayed Mathieu's equation which is used as an example. It is shown that an order reduction procedure in which only the dominant modes of the infinite-dimensional DDE are retained in the LFT is necessary. The application of the proposed technique is studied in the presence of delay and parametric resonances for the delayed Mathieu's equation, as well as for a double inverted pendulum subjected to a time-periodic retarded follower force.
Iron and ADHD
Authors: Donfrancesco Renato , Parisi Pasquale , Vanacore Nicola , Martines Francesca , Sargentini Vittorio , Cortese Samuele
Published: January 2012

Objective: (a) To compare serum ferritin levels in a sample of stimulant-naïve children with ADHD and matched controls and (b) to assess the association of serum ferritin to ADHD symptoms severity, ADHD subtypes, and IQ. Method: The ADHD and the control groups included 101 and 93 children, respectively. Serum ferritin levels were determined with the enzyme-linked immunosorbent assay method. Results: Serum ferritin did not significantly differ between children with ADHD and controls, as well as among ADHD subtypes. Correlations between serum ferritin levels and measures related to IQ or ADHD severity were not significant. Conclusion: This is the largest controlled study that assessed ferritin levels in stimulant-naïve ADHD children. The findings of this study do not support a significant relationship between serum ferritin levels and ADHD. However, the authors’ results based on peripheral measures of iron do not rule out a possible implication of brain iron deficiency in ADHD, grounded on neurobiological hypotheses and preliminary empirical evidence.
Self, Memory, and the Self-Reference Effect
Authors: Klein Stanley B.
Published: January 2012

The author argues that the self is a multifaceted entity that does not easily submit to clear and precise description. The aspect of self studied by most investigators is actually a subset of the cognitive and neural underpinnings of “self” and not the “self” of first-person subjectivity. The author then looks at the dominant theoretical treatment of human long-term memory—the systems approach—and examines how the construct of “self” is situated in this framework. Finally, he reviews the best-known paradigm for exploring the role of self in memory—the self-reference effect (SRE) manipulation. He argues that there is not one SRE but rather a family of related SREs that are influenced by a variety of variables and contexts. Accordingly, researchers must exercise caution when attempting to draw conclusions about the self from the results of SRE memory performance.
Queer filiations: Adaptation in the films of François Ozon
Authors: Handyside Fiona
Published: January 2012

The adaptation of canonical literary texts in cinema is often linked to a genre known as ‘heritage cinema’, a form associated especially with European cinema and used to promote a conservative vision of the nation as a site of heteronormative reproductive futurity. However, recalling Judith Butler's assertion that all repetition carries within it the possibility of subversion, and, furthermore, that subversion requires repetition, adaptation reappears as a potentially queer textual activity. As Linda Hutcheon argues, adaptation is ‘repetition without replication’. Through a close reading of differing modes and techniques of adaptation in the films of François Ozon, this article will demonstrate that adaptation offers the possibility of imagining new relationalities and affective encounters beyond the heteronormative reproduction of the nation state.
Leigh Bowery: Queer In fashion, queer in art
Authors: Bancroft Alison
Published: January 2012

This article considers questions raised by the fashion and performance artist Leigh Bowery (1961–1994) regarding the visual articulation of queer. Following Tim Dean, Joan Copjec and others, it predicates its reading on a particular definition of queer that comes from psychoanalysis, especially the theories of Jacques Lacan. I argue that Leigh Bowery is in fact a paradigm of queer sexualities when they are understood as an instance of transgressive jouissance. Bowery articulates visually precisely what cannot be uttered, and so represents the disruptive potential of fashion queered.
Cultural translation, politics of disempowerment and the reinvention of queer power and politics
Authors: Bourcier Marie-Hélène
Published: January 2012

This article addresses the task of describing the flows and trends of cultural translation of queer between the USA and Europe, particularly France. Firstly, it demonstrates how queer groups located in France re-translated ‘queer made in the USA’, inspired by continental philosophy, back into a French idiom in the mid-1990s. It then seeks to explain their contemporary responses to new trends and agendas in queer studies and politics that sound more and more compliant with ‘logics of disempowerment’. The re-sexualization and re-politicization of French post-structuralist philosophers and psychoanalysts such as Foucault, Deleuze, Derrida and Lacan, made possible by American queer theory and cultural studies, have been succeeded by a phase in which American theorists seem to crave the traditionally European privilege of being lauded as public intellectuals. At the beginning of the new century, a violent recodification by straight scholars and institutions took place and is still taking place in France: queer and post-colonial studies are dismissed or banned as subjective, unscientific agit prop. Today’s benevolent researchers reaffirm their power through powerlessness and ‘identify’ with the victims they defend. In this context, recent American queer theory and politics can give the impression of being driven by a logic of disempowerment. To illustrate this, Judith Butler’s Gender Trouble is compared with her Undoing Gender. Thus where Gender Trouble promoted strategies of resignification and resistance for both gender expression and hate speech, Undoing Gender displaces the strategy of resignification from hate speech to what could be called ‘master words’ such as ‘the universal’ and ‘the human’, and this ‘neo-universalism’ is linked to a politics of vulnerability. Moreover, whereas in Gender Trouble, textual or discursive performativity is impersonal and reversible, in Undoing Gender, the continental European figure of the philosopher is back. To counter this development, to pursue a strategy of dis-identification with the nation state and the United States, to quit the politics of vulnerability or desperation and to reverse the disempowering effects of the neo-assimilationist agenda, the article proposes a specifically French alternative. This consists of seeking to insert a queer version of what Félix Guattari calls ‘micropolitics’ into the macrocultural agenda of the LGBT right.
The construction of the black British community in The Voice and the New Nation
Authors: Prentoulis Marina
Published: January 2012

This article compares the way in which two black British tabloids, The Voice and the New Nation, construct the Afro-Caribbean community and their diasporic identities in the late 1990s, when the second title was launched. The analysis shows that The Voice reflects a more essentialist mode of thinking about Afro-Caribbean identities in Britain, contrary to the New Nation which questions this essentialist identity. While the essentialist mode was necessary for the politics of the early 1980s, when some form of equivalence had to be established between different black groups in the fight against racism, by the mid 1990s at least part of the black community had entered the middle-class mainstream. As a result, the New Nation focused on the achievements of this middle-class portion of the community and wanted to break free from the doom-and-gloom stories reflecting the experience of the 1980s. The starting point of this article is that media representations produce the framework of social cognition regarding black identities. The launch of the New Nation in 1996 signalled a new framework in which the diasporic imagination and the relationships between black and white communities and the relationship between race and class are re-examined.
Overpayment and Reservation Salary in the Nippon Professional Baseball League
Authors: Jane Wen-Jhan
Published: January 2012

This study examines predictions based on the job search model and estimates the overpayment within the labor market in Nippon Professional Baseball using stochastic frontier analysis. The empirical results indicate that more experienced players demand a higher reservation salary, and the effect increases at a decreasing rate. In the overpayment analysis, it is found that international players receive preferential labor market treatment. Moreover, from the analysis of team-level overpayments, payment wastage in terms of a team’s overpayment in a resource-abundant team within a large market (e.g., the Tokyo Giants) results in that team not being the most successful.
Abnormalities and Cue Dependence of Rhythmical Upper-Limb Movements in Parkinson Patients With Freezing of Gait
Authors: Vercruysse Sarah , Spildooren Joke , Heremans Elke , Vandenbossche Jochen , Wenderoth Nicole , Swinnen Stephan P. , Vandenberghe Wim , Nieuwboer Alice
Published: January 2012

Background. Freezing of gait (FOG) is a significant clinical problem in Parkinson disease (PD). Similar freezing-like episodes occur during finger movements, but little is known about ongoing motor problems during repetitive hand movements. Objective. To investigate if the regulation of bimanual movements is impaired in those with FOG and if withdrawal of an auditory cue amplifies this problem. Methods. A total of 23 PD patients (11 with and 12 without FOG) and 11 controls (CTRLs) performed repetitive finger movements, either externally paced or following cue withdrawal. Movement frequency, amplitude, and coordination pattern were manipulated. The stability and accuracy of movement were evaluated after exclusion of freezing trials. Results. With auditory pacing present, movement performance was comparable between groups. Following cue withdrawal, motor control deteriorated in those with FOG, resulting in smaller and less stable amplitudes, hastened and more variable frequency, and decreased coordination stability. Conversely, the performance of those without FOG remained mostly similar to that of CTRLs. Conclusions. Compared with those without FOG, those with FOG show greater continuous dyscontrol of bimanual movements, similar to the continuous timing and scaling difficulties during locomotion. Those with FOG also benefit from auditory cueing during upper-limb movements, but these are highly cue dependent. This implies that internal timekeeping functions are more disturbed in those with FOG, who may require rehabilitation strategies for repetitive upper-extremity tasks that include cueing and imagery.
Rare alpha-1-antitrypsin variants: are they really so rare?
Authors: Rodriguez-Frias Francisco , Miravitlles Marc , Vidal Rafael , Camos Silvia , Jardi Rosendo
Published: January 2012

Alpha-1-antitrypsin (α1-AT) deficiency is mainly evaluated in the diagnostic process of chronic obstructive pulmonary disease (COPD). Around 95% of individuals with severe α1-AT deficiency carry the PI*ZZ genotype. Little is known about the epidemiology of the remaining deficient α1-AT variants, which are called ‘rare’ due to their low prevalence. The retrospective revision of 3511 α1-AT deficiency determinations performed in Barcelona from 1998 to 2010 detected 1.6% of cases with rare α1-AT alleles, a rate similar to those reported in other European studies. Among these variants, PI*I and PI*Mmalton represented 54% of cases. Hence, the so-called ‘rare’ α1-AT alleles may not be rare as has been assumed. It would be of interest to implement simple allele-specific molecular biology methods to study the most prevalent rare variants in each region. Augmentation therapy is recommended in patients with emphysema and PI*ZZ genotype, but there is little evidence regarding the implications of rare variants on therapy.
Compartment-specific bioluminescence imaging platform for the high-throughput evaluation of antitumor immune function
Authors: McMillin Douglas W. , Delmore Jake , Negri Joseph M. , Vanneman Matthew , Koyama Shohei , Schlossman Robert L. , Munshi Nikhil C. , Laubach Jacob , Richardson Paul G. , Dranoff Glenn , Anderson Kenneth C. , Mitsiades Constantine S.
Published: January 2012

Conventional assays evaluating antitumor activity of immune effector cells have limitations that preclude their high-throughput application. We adapted the recently developed Compartment-Specific Bioluminescence Imaging (CS-BLI) technique to perform high-throughput quantification of innate antitumor activity and to show how pharmacologic agents (eg, lenalidomide, pomalidomide, bortezomib, and dexamethasone) and autologous BM stromal cells modulate that activity. CS-BLI–based screening allowed us to identify agents that enhance or inhibit innate antitumor cytotoxicity. Specifically, we identified compounds that stimulate immune effector cells against some tumor targets but suppressed their activity against other tumor cells. CS-BLI offers rapid, simplified, and specific evaluation of multiple conditions, including drug treatments and/or cocultures with stromal cells and highlights that immunomodulatory pharmacologic responses can be heterogeneous across different types of tumor cells. This study provides a framework to identify novel immunomodulatory agents and to prioritize compounds for clinical development on the basis of their effect on antitumor immunity.
Temporal transcriptome changes induced by MDV in marek's disease-resistant and -susceptible inbred chickens
Authors: Yu Ying , Luo Juan , Mitra Apratim , Chang Shuang , Tian Fei , Zhang Huanmin , Yuan Ping , Zhou Huaijun , Song Jiuzhou
Published: January 2012

Background

Marek's disease (MD) is a lymphoproliferative disease in chickens caused by Marek's disease virus (MDV) and characterized by T cell lymphoma and infiltration of lymphoid cells into various organs such as liver, spleen, peripheral nerves and muscle. Resistance to MD and disease risk have long been thought to be influenced both by genetic and environmental factors, the combination of which contributes to the observed outcome in an individual. We hypothesize that after MDV infection, genes related to MD-resistance or -susceptibility may exhibit different trends in transcriptional activity in chicken lines having a varying degree of resistance to MD.

Results

In order to study the mechanisms of resistance and susceptibility to MD, we performed genome-wide temporal expression analysis in spleen tissues from MD-resistant line 63, susceptible line 72and recombinant congenic strain M (RCS-M) that has a phenotype intermediate between lines 63and 72after MDV infection. Three time points of the MDV life cycle in chicken were selected for study: 5 days post infection (dpi), 10dpi and 21dpi, representing the early cytolytic, latent and late cytolytic stages, respectively. We observed similar gene expression profiles at the three time points in line 63and RCS-M chickens that are both different from line 72. Pathway analysis using Ingenuity Pathway Analysis (IPA) showed that MDV can broadly influence the chickens irrespective of whether they are resistant or susceptible to MD. However, some pathways like cardiac arrhythmia and cardiovascular disease were found to be affected only in line 72; while some networks related to cell-mediated immune response and antigen presentation were enriched only in line 63and RCS-M. We identified 78 and 30 candidate genes associated with MD resistance, at 10 and 21dpi respectively, by considering genes having the same trend of expression change after MDV infection in lines 63and RCS-M. On the other hand, by considering genes with the same trend of expression change after MDV infection in lines 72and RCS-M, we identified 78 and 43 genes at 10 and 21dpi, respectively, which may be associated with MD-susceptibility.

Conclusions

By testing temporal transcriptome changes using three representative chicken lines with different resistance to MD, we identified 108 candidate genes for MD-resistance and 121 candidate genes for MD-susceptibility over the three time points. Genes included in our resistance or susceptibility genes lists that are also involved in more than 5 biofunctions, such asCD8α,IL8,USP18, andCTLA4, are considered to be important genes involved in MD-resistance or -susceptibility. We were also able to identify several biofunctions related with immune response that we believe play an important role in MD-resistance.
Genome-wide landscape of liver X receptor chromatin binding and gene regulation in human macrophages
Authors: Pehkonen Petri , Welter-Stahl Lynn , Diwo Janine , Ryynänen Jussi , Wienecke-Baldacchino Anke , Heikkinen Sami , Treuter Eckardt , Steffensen Knut R , Carlberg Carsten
Published: January 2012

Background

The liver X receptors (LXRs) are oxysterol sensing nuclear receptors with multiple effects on metabolism and immune cells. However, the complete genome-wide cistrome of LXR in cells of human origin has not yet been provided.

Results

We performed ChIP-seq in phorbol myristate acetate-differentiated THP-1 cells (macrophage-type) after stimulation with the potent synthetic LXR ligand T0901317 (T09). Microarray gene expression analysis was performed in the same cellular model. We identified 1357 genome-wide LXR locations (FDR < 1%), of which 526 were observed after T09 treatment.De novoanalysis of LXR binding sequences identified a DR4-type element as the major motif. On mRNA level T09 up-regulated 1258 genes and repressed 455 genes. Our results show that LXR actions are focused on 112 genomic regions that contain up to 11 T09 target genes per region under the control of highly stringent LXR binding sites with individual constellations for each region. We could confirm that LXR controls lipid metabolism and transport and observed a strong association with apoptosis-related functions.

Conclusions

This first report on genome-wide binding of LXR in a human cell line provides new insights into the transcriptional network of LXR and its target genes with their link to physiological processes, such as apoptosis.

The gene expression microarray and sequence data have been submitted collectively to the NCBI Gene Expression Omnibushttp://www.ncbi.nlm.nih.gov/geounder accession number GSE28319.
Adoptive transfer of IL-4Rα+ macrophages is sufficient to enhance eosinophilic inflammation in a mouse model of allergic lung inflammation
Authors: Ford Andrew Q , Dasgupta Preeta , Mikhailenko Irina , Smith Elizabeth MP , Noben-Trauth Nancy , Keegan Achsah D
Published: January 2012

Background

The IL-4 receptor α (IL-4Rα) chain has a broad expression pattern and participates in IL-4 and IL-13 signaling, allowing it to influence several pathological components of allergic lung inflammation. We previously reported that IL-4Rα expression on both bone marrow-derived and non-bone marrow-derived cells contributed to the severity of allergic lung inflammation. There was a correlation between the number of macrophages expressing the IL-4Rα, CD11b, and IAd, and the degree of eosinophilia in ovalbumin challenged mice. The engagement of the IL-4Rα by IL-4 or IL-13 is able to stimulate the alternative activation of macrophages (AAM). The presence of AAM has been correlated with inflammatory responses to parasites and allergens. Therefore, we hypothesized that IL-4Rα+AAM play an active role in allergic lung inflammation. To directly determine the role of AAM in allergic lung inflammation, M-CSF-dependent macrophages (BMM) were prepared from the bone-marrow of IL-4Rα positive and negative mice and transferred to IL-4RαxRAG2-/-mice. Wild type TH2 cells were provided exogenously.

Results

Mice receiving IL-4Rα+/+BMM showed a marked increase in the recruitment of eosinophils to the lung after challenge with ovalbumin as compared to mice receiving IL-4Rα-/-BMM. As expected, the eosinophilic inflammation was dependent on the presence of TH2 cells. Furthermore, we observed an increase in cells expressing F4/80 and Mac3, and the AAM marker YM1/2 in the lungs of mice receiving IL-4Rα+/+BMM. The BAL fluid from these mice contained elevated levels of eotaxin-1, RANTES, and CCL2.

Conclusions

These results demonstrate that transfer of IL-4Rα + macrophages issufficientto enhance TH2-driven, allergic inflammation. They further show that stimulation of macrophages through IL-4Rα leads to their alternative activation andpositive contributionto the TH2-driven allergic inflammatory response in the lung. Since an increase in AAM and their products has been observed in patients with asthma exacerbations, these results suggest that AAM may be targeted to alleviate exacerbations.
Transcriptional activation of microRNA-34a by NF-kappa B in human esophageal cancer cells
Authors: Li Juan , Wang Kai , Chen Xuedan , Meng Hui , Song Min , Wang Yan , Xu Xueqing , Bai Yun
Published: January 2012

Background

miR-34a functions as an important tumor suppressor during the process of carcinogenesis. However, the mechanism of miR-34a dysregulation in human malignancies has not been well elucidated. Our study aimed to further investigate the regulation mechanism of miR-34a.

Results

We found that overexpression of NF-kappa B p65 subunit could increase miR-34a levels in EC109, an esophageal squamous cancer cell line, while ectopic expression of DN IkappaB leaded to a significant reduction of miR-34a expression. Bioinformatics analysis suggested three putative KB sites in promoter region of miR-34a gene. Mutation two of these KB sites impaired p65 induced miR-34a transcriptional activity. Chromatin immunoprecipitation and electrophoretic mobility shift assays both showed that NF-kappaB could specifically bind to the third KB site located in miR-34a promoter. In addition, we found that overexpression of NF-kappaB p65 could not successfully induce miR-34a expression in esophageal cancer cell lines with mutant p53 or decreased p53. Reporter assay further showed that NF-kappaB-induced miR-34a transcriptional activity was reduced by p53 impairment. Nevertheless, CHIP analysis suggested binding of NF-kappaB to miR-34a promoter was not affected in cells with mutant p53.

Conclusions

Our work indicates a novel mechanism of miR-34a regulation that NF-kappaB could elevate miR-34a expression levels through directly binding to its promoter. And wildtype p53 is responsible for NF-kappaB-mediated miR-34a transcriptional activity but not for NF-kappaB binding. These findings might be helpful in understanding miR-34a abnormality in human malignancies and open new perspectives for the roles of miR-34a and NF-kappaB in tumor progression.
Long-term effects of treatment and response in patients with chronic hepatitis C on quality of life. An international, multicenter, randomized, controlled study
Authors: Bezemer Geert , Van Gool Arthur R , Verheij-Hart Elke , Hansen Bettina E , Lurie Yoav , Esteban Juan I , Lagging Martin , Negro Francesco , Zeuzem Stefan , Ferrari Carlo , Pawlotsky Jean-Michel , Neumann Avidan U , Schalm Solko W , de Knegt Robert J ,   for the DITTO-HCV Study Group
Published: January 2012

Background

Hepatitis C decreases health related quality of life (HRQL) which is further diminished by antiviral therapy. HRQL improves after successful treatment. This trial explores the course of and factors associated with HRQL in patients given individualized or standard treatment based on early treatment response (Ditto-study).

Methods

The Short Form (SF)-36 Health Survey was administered at baseline (n = 192) and 24 weeks after the end of therapy (n = 128).

Results

At baseline HRQL was influenced by age, participating center, severity of liver disease and income. Exploring the course of HRQL (scores at follow up minus baseline), only the dimension general health increased. In this dimension patients with a relapse or sustained response differed from non-responders. Men and women differed in the dimension bodily pain. Treatment schedule did not influence the course of HRQL.

Conclusions

Main determinants of HRQL were severity of liver disease, age, gender, participating center and response to treatment. Our results do not exclude a more profound negative impact of individualized treatment compared to standard, possibly caused by higher doses and extended treatment duration in the individualized group. Antiviral therapy might have a more intense and more prolonged negative impact on females.
Cancer-initiating cells derived from established cervical cell lines exhibit stem-cell markers and increased radioresistance
Authors: López Jacqueline , Poitevin Adela , Mendoza-Martínez Veverly , Pérez-Plasencia Carlos , García-Carrancá Alejandro
Published: January 2012

Background

Cancer-initiating cells (CICs) are proposed to be responsible for the generation of metastasis and resistance to therapy. Accumulating evidences indicates CICs are found among different human cancers and cell lines derived from them. Few studies address the characteristics of CICs in cervical cancer. We identify biological features of CICs from four of the best-know human cell lines from uterine cervix tumors. (HeLa, SiHa, Ca Ski, C-4 I).

Methods

Cells were cultured as spheres under stem-cell conditions. Flow cytometry was used to detect expression of CD34, CD49f and CD133 antigens and Hoechst 33342 staining to identify side population (SP). Magnetic and fluorescence-activated cell sorting was applied to enrich and purify populations used to evaluate tumorigenicity in nude mice. cDNA microarray analysis and in vitro radioresistance assay were carried out under standard conditions.

Results

CICs, enriched as spheroids, were capable to generate reproducible tumor phenotypes in nu-nu mice and serial propagation. Injection of 1 × 103 dissociated spheroid cells induced tumors in the majority of animals, whereas injection of 1 × 105 monolayer cells remained nontumorigenic. Sphere-derived CICs expressed CD49f surface marker. Gene profiling analysis of HeLa and SiHa spheroid cells showed up-regulation of CICs markers characteristic of the female reproductive system. Importantly, epithelial to mesenchymal (EMT) transition-associated markers were found highly expressed in spheroid cells. More importantly, gene expression analysis indicated that genes required for radioresistance were also up-regulated, including components of the double-strand break (DSB) DNA repair machinery and the metabolism of reactive oxygen species (ROS). Dose-dependent radiation assay indicated indeed that CICs-enriched populations exhibit an increased resistance to ionizing radiation (IR).

Conclusions

We characterized a self-renewing subpopulation of CICs found among four well known human cancer-derived cell lines (HeLa, SiHa, Ca Ski and C-4 I) and found that they express characteristic markers of stem cell, EMT and radioresistance. The fact that CICs demonstrated a higher degree of resistance to radiation than differentiated cells suggests that specific detection and targeting of CICs could be highly valuable for the therapy of tumors from the uterine cervix.