bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Localization Techniques in the Diagnosis and Characterization of Nonhuman Primate Infectious Diseases
Authors: Mansfield K. G. , Sasseville V. G. , Westmoreland S. V.
Published: October 2013

Molecular localization techniques remain important diagnostic and research tools for the pathologist evaluating nonhuman primate tissues. In situ hybridization and immunohistochemistry protocols have been developed for many important pathogens of nonhuman primates, including RNA and DNA viruses, prions, and bacterial, protozoal, and fungal pathogens. Such techniques will remain critical in defining the impact and relevance of novel agents on animal health and disease. A comparative pathology perspective often provides valuable insight to the best strategy for reagent development and can also facilitate interpretation of molecular localization patterns. Such a perspective is grounded in a firm understanding of microbe-host pathobiology. This review summarizes current molecular localization protocols used in the diagnosis of selected primate infectious diseases.
Effects of a Supplemental Intervention Focused in Equivalency Concepts for Students With Varying Abilities
Authors: Hunt Jessica H.
Published: October 2013

The purpose of this study was to examine the effects of a Tier 2 supplemental intervention focused on rational number equivalency concepts and applications on the mathematics performance of third-grade students with and without mathematics difficulties. The researcher used a pretest–posttest control group design and random assignment of 19 participants to core instruction and 19 participants to core + intervention instruction. Intervention instruction included the ratio interpretation of rational number in conjunction with explicit and conceptual instructional components—judicious review opportunities, concrete and visual representations, systematic task progression focused on big ideas, teacher and student verbalizations, and multiple opportunities for practice—to deliver a sequence of 20 intervention sessions over a period of 4 weeks. Students receiving core instruction plus intervention outperformed those receiving only core instruction on a standard measure of the intervention content as well as a pretest–posttest measure reflective of the core curriculum.
Churg-Strauss Syndrome in Childhood
Authors: Albahri Ziad , Minxová Lenka , Lukeš Antonín , Mawiri Abdul AL. , Štefáčková Šárka
Published: October 2013

Churg-Strauss syndrome is a rare form of small-vessel vasculitis. In the current report, we describe the case of a 17-year-old Czech girl predominantly characterized by peripheral neuropathy, the presence of cardiac and pulmonary involvement, hypereosinophilia, asthma, and sinusitis that led to the diagnosis of Churg-Strauss syndrome.
Malnutrition in Cystic Fibrosis
Authors: Culhane Suzanne , George Carolyn , Pearo Brittany , Spoede Elizabeth
Published: October 2013

Malnutrition is one of the main burdens of disease in cystic fibrosis (CF) along with lung disease. Data from the most recent Cystic Fibrosis Foundation registry report show the prevalence of malnutrition is decreasing in the CF population primarily from interventions focusing on preventing malnutrition. Despite success of interventions and decreased prevalence of malnutrition in this population, prevention of malnutrition in CF patients remains a dilemma that must be managed throughout the life cycle. The pathogenesis of malnutrition in CF can be further categorized into 3 main areas: increased energy losses, increased energy needs, and inadequate calorie intake. The purpose of this review is to further explore the causes of malnutrition and explain current research to prevent malnutrition in the CF population.
Differentiation and Eating Disorder Symptoms Among Males
Authors: Buser Juleen K. , Gibson Sandy
Published: October 2013

We explored the relationship between four domains of differentiation of self and eating disorder symptoms among male college students. While all differentiation domains were significantly correlated with eating disorder symptoms, only two domains were statistically significant in a regression. Drawing from these results, we discuss family counseling implications.
Force and ground vibration reduction of railway tracks with elastic elements
Authors: Auersch Lutz
Published: October 2013

The reduction of train-induced ground vibration by elastic elements such as rail pads and sleeper pads has been analyzed by a combined finite-element boundary-element method. The dynamic compliance of the track, the transfer function of the total force on the ground and the ground vibration ratios have been calculated for a variety of isolated and un-isolated track systems. It has been found that the soil force transfer, which describes the excitation force of the soil, is an appropriate quantity to predict the reduction of the ground vibration and the effectiveness of isolated tracks. All force transfer functions of isolated tracks display a vehicle–track resonance where the wheelset on the compliant track is excited by wheel and track irregularities. At higher frequencies, considerable reductions of the amplitudes are observed as the benefit of the resilient element. The influence of the stiffness of the rail or sleeper pads, the ballast and the soil, and the mass of the sleeper and the wheelset on the resonance frequency and the reduction has been investigated. Sleeper pads are advantageous due to the higher mass that is elastically supported compared to the rail-pad track system. The combination of elastic rail and sleeper pads has been found to be disadvantageous, as the second resonance occurs in the frequency range of intended reduction.
Hunting Roaches
Authors: Badley Graham Francis
Published: October 2013

I have borrowed two images from Graham Greene. The first, hunting roaches, is a metaphor for attacking my own failures as a scholar. The second becomes a subtitle for this attempt to summarize a sorting of my academic life. I first explain why I have rejected autobiography, autoethnography, and mystory in favor of using Greene’s “sort of life” as a way of structuring my scrappy academic experiences. I then use another set of apparently frivolous metaphors to organize the reflective telling of my sort of academic life. These metaphors or processes are presented as a series of life phases: scrabbling, scribbling, scribing, and scrubbing. They are interrupted by a separate “doing nothing” phase, which is a commentary on a chronic case of writer’s block. Finally, I reflect on two more hopeful phases of my sort of life that I identify as usefully “frivolous” and fruitfully “post-academic.”
Incentives for improving human resource outcomes in health care: overview of reviews
Authors: Misfeldt Renee , Linder Jordana , Lait Jana , Hepp Shelanne , Armitage Gail , Jackson Karen , Suter Esther
Published: October 2013

Objectives

To review the effectiveness of financial and nonfinancial incentives for improving the benefits (recruitment, retention, job satisfaction, absenteeism, turnover, intent to leave) of human resource strategies in health care.

Methods

Overview of 33 reviews published from 2000 to 2012 summarized the effectiveness of incentives for improving human resource outcomes in health care (such as job satisfaction, turnover rates, recruitment, and retention) that met the inclusion criteria and were assessed by at least two research members using the Assessment of Multiple Systematic Reviews quality assessment tool. Of those, 13 reviews met the quality criteria and were included in the overview. Information was extracted on a description of the review, the incentives considered, and their impact on human resource outcomes. The information on the relationship between incentives and outcomes was assessed and synthesized.

Results

While financial compensation is the best-recognized approach within an incentives package, there is evidence that health care practitioners respond positively to incentives linked to the quality of the working environments including opportunities for professional development, improved work life balance, interprofessional collaboration, and professional autonomy. There is less evidence that workload factors such as job demand, restructured staffing models, re-engineered work designs, ward practices, employment status, or staff skill mix have an impact on human resource outcomes.

Conclusions

Overall, evidence of effective strategies for improving outcomes is mixed. While financial incentives play a key role in enhancing outcomes, they need to be considered as only one strategy within an incentives package. There is stronger evidence that improving the work place environment and instituting mechanisms for work-life balance need to be part of an overall strategy to improve outcomes for health care practitioners.
Linagliptin added to sulphonylurea in uncontrolled type 2 diabetes patients with moderate-to-severe renal impairment
Authors: McGill Janet B , Barnett Anthony H , Lewin Andrew J , Patel Sanjay , Neubacher Dietmar , von Eynatten Maximilian , Woerle Hans-Juergen
Published: October 2013

Glucose-lowering treatment options are limited for uncontrolled type 2 diabetes mellitus (T2DM) patients with advanced stages of renal impairment (RI). This retrospective analysis evaluated glycaemic efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor linagliptin added to sulphonylurea. Three randomized phase 3 studies ( n = 619) including T2DM subjects with moderate or severe RI [estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2] were analysed; only sulphonylurea-treated subjects who received additional linagliptin ( n = 58) or placebo ( n = 33) were evaluated. Linagliptin provided meaningful placebo-adjusted HbA1c reductions of −0.68% (95% confidence interval: −1.19, −0.17), −1.08% (−2.02, −0.14) and −0.62% (−1.25, 0.01) after 24, 18 and 12 weeks, respectively. There was a similar incidence of overall adverse events (linagliptin: 79.3%, placebo: 75.8%) and hypoglycaemia (linagliptin: 37.9%, placebo: 39.4%). Severe hypoglycaemia was more common with placebo (linagliptin: 1.7%, placebo: 6.1%). These data suggest that linagliptin is a safe and effective glucose-lowering treatment in T2DM patients with moderate-to-severe RI for whom sulphonylurea treatment is no longer sufficient.
Investigation of endothelial dysfunction and arterial stiffness in children with type 1 diabetes mellitus and the association with diastolic dysfunction
Authors: Çiftel Murat , Ertuğ Halil , Parlak Mesut , Akçurin Gayaz , Kardelen Fırat
Published: October 2013

Objective:

The objective of this study is to investigate endothelial dysfunction (ED) and arterial stiffness (AS) and determine the association with diastolic dysfunction in children with type 1 diabetes mellitus (DM).

Methods:

A total of 42 patients without diabetic complications (mean age: 13.21 years) and 40 healthy (mean age: 13.07 years) children were included in this study. AS was assessed with ascending aorta M-mode measurements, diastolic dysfunction with pulsed wave (PW) Doppler and tissue Doppler echocardiography measurements and flow-mediated dilatation (FMD) and carotid intima–media thickness (CIMT) with high-resolution ultrasonography.

Results:

Results of diabetic group and healthy children were compared. In diabetic group, aortic strain (8.40 ± 2.98, 20.12 ± 5.04; p < 0.001), aortic distensibility (7.36 ± 2.92, 16.59 ± 4.25; p < 0.001) and FMD% (7.70 ± 2.83, 11.33 ± 2.85; p < 0.001) were found decreased, and CIMT (0.52 ± 0.09 mm, 0.47 ± 0.08 mm; p < 0.05) was found increased. Additionally, left ventricular lateral segment and right ventricular free-wall isovolumic relaxation time (IVRT) and myocardial performance index (MPI) were found increased. Correlation analyses demonstrated a negative correlation between FMD and IVRT and MPI.

Conclusions:

ED and AS were found in type 1 DM patients without diabetic complications. Additionally, correlation was shown between increased AS and ED and right and left ventricular diastolic dysfunctions.
Comparing the effects of instructional and transformational leadership on student achievement
Authors: Shatzer Ryan H , Caldarella Paul , Hallam Pamela R , Brown Bruce L
Published: October 2013

The purpose of this study was to compare transformational and instructional leadership theories, examine the unique impact that school leaders have on student achievement, and determine which specific leadership practices are associated with increased student achievement. The sample for this study consisted of 590 teachers in 37 elementary schools in the Intermountain West of the United States. Teachers rated their principals’ leadership style according to the Multifactor Leadership Questionnaire (Transformational Leadership) and the Principal Instructional Management Rating Scale (Instructional leadership). Student achievement was measured by a criterion referenced test. Hypotheses were tested using regression analysis. Results indicated that instructional leadership explained more of the variance in student achievement than did transformational leadership. Principals’ leadership style tended to have a meaningful impact on student achievement beyond the impact of school context and principal demographics. Specific leadership functions associated with student achievement were also identified and reported. Conclusion, implications and limitations are also discussed.
Leading for sustainability in Western Australian regional schools
Authors: Pepper Coral
Published: October 2013

In this paper I report on leadership for sustainability in regional schools in Western Australia (WA) in the context of the Australian Sustainable Schools Initiative (AuSSI-WA). Case studies are developed to examine leading cultural change in eight WA regional schools with data presented in three representative narrative accounts. Consistency is apparent across the study as school leaders occupying both formal and informal leadership positions articulate a desire to bring about change and represent an explicit shift towards sustainability in these regional schools. In the main, these school leaders envision their schools as a place where the community works for a sustainable future; they are firm in their belief that responsibility for change is to be shared and; they recognise the importance of strategies to introduce and embed change in their schools. Such findings have implications for whole of school approaches to embedding change in our schools.
Precautionary tales: Suspicionless counter-terrorism stop and search
Authors: Lennon Genevieve
Published: October 2013

In recent years, there has been an increased focus on the use of the precautionary principle within counter-terrorism. To date much of the literature has focused on ‘high’ level executive measures. This article examines the use of the precautionary measures within counter-terrorism street policing, taking suspicionless counter-terrorism stop and search as an exemplar. The analysis highlights how the logic of precaution necessitates vague statutory drafting and extensive police discretion and how these factors detrimentally impact upon police legitimacy and compliance to human rights law. It also considers how such measures fit within the current literature on pre-crime.
Avascular Necrosis of Femoral Head
Authors: Mallina Ravi , Dinah Feroz
Published: October 2013

Avascular necrosis (AVN) of the femoral head is a relatively uncommon complication following an extracapsular hip fracture. Although it can occur following fixation of unstable 3-part or 4-part intertrochanteric fractures with significant posteromedial and posterolateral comminution, it remains a rare complication. We present a case of AVN of the femoral head following fixation of a stable 2-part intertrochanteric fracture in spite of good healing at the hip fracture site. This is a rare but eminently treatable cause of persisting hip pain after hip fracture surgery, and primary or secondary care physicians should be aware of this possibility.
The Myc-miR-17-92 axis amplifies B-cell receptor signaling via inhibition of ITIM proteins: a novel lymphomagenic feed-forward loop
Authors: Psathas James N. , Doonan Patrick J. , Raman Pichai , Freedman Bruce D. , Minn Andy J. , Thomas-Tikhonenko Andrei
Published: October 2013

Key Points

Myc amplifies BCR signaling and increases its own levels via upregulation of miR-17∼92 and subsequent targeting of ITIM proteins. Inhibition of miR-17∼92 in DLBCL cell lines dampens the BCR response; DLBCL tumors of the BCR subtype have elevated levels of miR-17∼92.
Common low-penetrance risk variants associated with breast cancer in Polish women
Authors: Ledwoń Joanna K , Hennig Ewa E , Maryan Natalia , Goryca Krzysztof , Nowakowska Dorota , Niwińska Anna , Ostrowski Jerzy
Published: October 2013

Background

Breast cancer is the most common type of cancer and the second leading cause of cancer-death among women in Poland. The known high-risk mutations account for 25% of familial aggregation cases and 5% of total breast cancer predisposition. Genome-wide association studies have identified a number of common low-penetrance genetic variants, but their contribution to disease risk differs between populations.

Methods

To verify selected associations with breast cancer susceptibility among Polish women, the replication study was performed, included 1424 women with breast cancer and 1788 healthy persons. Sixteen single-nucleotide polymorphisms (SNPs) were analyzed using TaqMan SNP Genotyping Assays. Allele frequency differences were tested using chi2-test implemented in PLINK v1.07 and Cochran-Armitage trend test was performed using R software.

Results

Significant differences (Bonferroni corrected p-valuecor ≤ 0.0197) in the frequency of alleles distribution between all cancer and control subjects were observed for four (rs2736098, rs13281615, rs1219648, rs2981582) out of 16 SNPs. The same result was obtained for group of patients without high-risk BRCA1/2 mutations. The rs1219648 (p-valuecor ≤ 6.73E-03) and rs2981582 (p-valuecor ≤ 6.48E-03) SNPs showed significant association with both familial and sporadic cancers. Additionally, rs2736098 (p-valuecor ≤ 0.0234) was associated with only sporadic cancers; also in group without carriers of high-risk mutation. All these associations revealed their significance also in Cochran-Armitage trend test. Opposite to other SNPs, rs2736098 was associated with a decreased risk of breast cancer.

Conclusion

The association of four known susceptibility SNPs, representing three individual loci, with breast cancer risk in Polish women was confirmed. One of them (rs2736098) seems to be specific for the Polish population. Due to the population differences in allele frequencies, identification of general genetic risk factors requires sets of association studies conducted on different populations.
Epidemiology of malaria in an area of seasonal transmission in Niger and implications for the design of a seasonal malaria chemoprevention strategy
Authors: Guillebaud Julia , Mahamadou Aboubacar , Zamanka Halima , Katzelma Mariama , Arzika Ibrahim , Ibrahim Maman L , Eltahir Elfatih Ab , Labbo Rabiou , Druilhe Pierre , Duchemin Jean-Bernard , Fandeur Thierry
Published: October 2013

Background

Few data are available about malaria epidemiological situation in Niger. However, implementation of new strategies such as vaccination or seasonal treatment of a target population requires the knowledge of baseline epidemiological features of malaria. A population-based study was conducted to provide better characterization of malaria seasonal variations and population groups the most at risk in this particular area.

Methods

From July 2007 to December 2009, presumptive cases of malaria among a study population living in a typical Sahelian village of Niger were recorded, and confirmed by microscopic examination. In parallel, asymptomatic carriers were actively detected at the end of each dry season in 2007, 2008 and 2009.

Results

Among the 965 presumptive malaria cases recorded, 29% were confirmed by microscopic examination. The incidence of malaria was found to decrease significantly with age (p < 0.01). The mean annual incidence was 0.254. The results show that the risk of malaria was higher in children under ten years (p < 0.0001). The number of malaria episodes generally followed the temporal pattern of changes in precipitation levels, with a peak of transmission in August and September. One-thousand and ninety subjects were submitted to an active detection of asymptomatic carriage of whom 16% tested positive; asymptomatic carriage decreased with increasing age. A higher prevalence of gametocyte carriage among asymptomatic population was recorded in children aged two to ten years, though it did not reach significance.

Conclusions

In Southern Niger, malaria transmission mostly occurs from July to October. Children aged two to ten years are the most at risk of malaria, and may also represent the main reservoir for gametocytes. Strategies such as intermittent preventive treatment in children (IPTc) could be of interest in this area, where malaria transmission is highly seasonal. Based on these preliminary data, a pilot study could be implemented in Zindarou using IPTc targeting children aged two to ten years, during the three months of malaria transmission, together with an accurate monitoring of drug resistance.
The CONSORT Patient-Reported Outcome (PRO) extension: implications for clinical trials and practice
Authors: Calvert Melanie , Brundage Michael , Jacobsen Paul B , Schünemann Holger J , Efficace Fabio
Published: October 2013

To inform clinical guidelines and patient care we need high quality evidence on the relative benefits and harms of intervention. Patient reported outcome (PRO) data from clinical trials can “empower patients to make decisions based on their values” and “level the playing field between physician and patient”. While clinicians have a good understanding of the concept of health-related quality of life and other PROs, evidence suggests that many do not feel comfortable in using the data from trials to inform discussions with patients and clinical practice. This may in part reflect concerns over the integrity of the data and difficulties in interpreting the results arising from poor reporting.

The new CONSORT PRO extension aims to improve the reporting of PROs in trials to facilitate the use of results to inform clinical practice and health policy. While the CONSORT PRO extension is an important first step in the process, we need broader engagement with the guidance to facilitate optimal reporting and maximize use of PRO data in a clinical setting. Endorsement by journal editors, authors and peer reviewers are crucial steps. Improved design, implementation and transparent reporting of PROs in clinical trials are necessary to provide high quality evidence to inform evidence synthesis and clinical practice guidelines.
Reduced cerebral blood flow and white matter hyperintensities predict poor sleep in heart failure
Authors: Alosco Michael L , Brickman Adam M , Spitznagel Mary Beth , Griffith Erica Y , Narkhede Atul , Cohen Ronald , Sweet Lawrence H , Hughes Joel , Rosneck Jim , Gunstad John
Published: October 2013

Background

Poor sleep is common in heart failure (HF), though mechanisms of sleep difficulties are not well understood. Adverse brain changes among regions important for sleep have been demonstrated in patients with HF. Cerebral hypoperfusion, a correlate of sleep quality, is also prevalent in HF and a likely contributor to white matter hyperintensities (WMH). However, no study to date has examined the effects of cerebral blood flow, WMH, and brain volume on sleep quality in HF.

Methods

Fifty-three HF patients completed the Pittsburgh Sleep Quality Index and underwent brain magnetic resonance imaging to quantify brain and WMH volume. Transcranial Doppler ultrasonography assessed cerebral blood flow velocity of the middle cerebral artery (CBF-V of the MCA).

Results

75.5% of HF patients reported impaired sleep. Regression analyses adjusting for medical and demographic factors showed decreased CBF-V of the MCA and greater WMH volume were associated with poor sleep quality. No such pattern emerged on total brain or regional volume indices.

Conclusions

Decreased cerebral perfusion and greater WMH may contribute to sleep difficulties in HF. Future studies are needed to confirm these findings and clarify the effects of cerebral blood flow and WMH on sleep in healthy and patient samples.
Evaluating the prophylaxis and long-term effectiveness of acupuncture for migraine without aura: study protocol for a randomized controlled trial
Authors: Chen Jiao , Zhao Ling , Zheng Hui , Li Ying , Yang Mingxiao , Chang Xiaorong , Gong Biao , Huang Yinlan , Liu Yanqin , Liang Fanrong
Published: October 2013

Background

The instant-treatment effect of acupuncture for patients with migraines has been corroborated in numerous studies. However, most diseases are chronic and tend to recur, so the long-term effect of acupuncture can verify the existence of sustained efficacy or the placebo effect. Evaluating the efficacy of acupuncture in the prophylaxis of migraine without aura (MWoA) in China is also important because such studies are lacking.

Methods

This trial is a multicenter, prospective, pragmatic randomized controlled clinical trial. We will randomly allocate 249 participants to three groups of 83. Patients in the individualized acupoint group will be treated with individualized acupuncture point prescriptions. The non-acupoint control group will undergo insertion of acupuncture needles at four bilateral non-points in locations not corresponding to acupuncture points. The waiting-list control group will not undergo treatment but instead will receive 20 acupuncture treatments for free after a waiting period of 24 weeks. Participants in the individualized acupoint group and non-acupoint control group will receive 20 sessions over four weeks and then all participants will receive 20 weeks of follow-up.

Discussion

The results of our trial will help to supply evidence for the long-term acupuncture effect for MWoA in a long follow-up period, and special attention will be paid to comparison with the placebo effect.

Trial registration

The trial was registered at ClinicalTrials.gov (NCT01687660) on 18 September 2012.
Quantitative structure-activation barrier relationship modeling for Diels-Alder ligations utilizing quantum chemical structural descriptors
Authors: Nandi Sisir , Monesi Alessandro , Drgan Viktor , Merzel Franci , Novič Marjana
Published: October 2013

Background

In the present study, we show the correlation of quantum chemical structural descriptors with the activation barriers of the Diels-Alder ligations. A set of 72 non-catalysed Diels-Alder reactions were subjected to quantitative structure-activation barrier relationship (QSABR) under the framework of theoretical quantum chemical descriptors calculated solely from the structures of diene and dienophile reactants. Experimental activation barrier data were obtained from literature. Descriptors were computed using Hartree-Fock theory using 6-31G(d) basis set as implemented in Gaussian 09 software.

Results

Variable selection and model development were carried out by stepwise multiple linear regression methodology. Predictive performance of the quantitative structure-activation barrier relationship (QSABR) model was assessed by training and test set concept and by calculating leave-one-out cross-validated Q2 and predictive R2 values. The QSABR model can explain and predict 86.5% and 80% of the variances, respectively, in the activation energy barrier training data. Alternatively, a neural network model based on back propagation of errors was developed to assess the nonlinearity of the sought correlations between theoretical descriptors and experimental reaction barriers.

Conclusions

A reasonable predictability for the activation barrier of the test set reactions was obtained, which enabled an exploration and interpretation of the significant variables responsible for Diels-Alder interaction between dienes and dienophiles. Thus, studies in the direction of QSABR modelling that provide efficient and fast prediction of activation barriers of the Diels-Alder reactions turn out to be a meaningful alternative to transition state theory based computation.
New mutations in flagellar motors identified by whole genome sequencing in Chlamydomonas
Authors: Lin Huawen , Nauman Nicholas P , Albee Alison J , Hsu Silas , Dutcher Susan K
Published: October 2013

Background

The building of a cilium or flagellum requires molecular motors and associated proteins that allow the relocation of proteins from the cell body to the distal end and the return of proteins to the cell body in a process termed intraflagellar transport (IFT). IFT trains are carried out by kinesin and back to the cell body by dynein.

Methods

We used whole genome sequencing to identify the causative mutations for two temperature-sensitive flagellar assembly mutants in Chlamydomonas and validated the changes using reversion analysis. We examined the effect of these mutations on the localization of IFT81, an IFT complex B protein, the cytoplasmic dynein heavy chain (DHC1b), and the dynein light intermediate chain (D1bLIC).

Results

The strains, fla18 and fla24, have mutations in kinesin-2 and cytoplasmic dynein, respectively. The fla18 mutation alters the same glutamic acid (E24G) mutated in the fla10-14 allele (E24K). The fla18 strain loses flagella at 32°C more rapidly than the E24K allele but less rapidly than the fla10-1 allele. The fla18 mutant loses its flagella by detachment rather than by shortening. The fla24 mutation falls in cytoplasmic dynein and changes a completely conserved amino acid (L3243P) in an alpha helix in the AAA5 domain. The fla24 mutant loses its flagella by shortening within 6 hours at 32°C. DHC1b protein is reduced by 18-fold and D1bLIC is reduced by 16-fold at 21°C compared to wild-type cells. We identified two pseudorevertants (L3243S and L3243R), which remain flagellated at 32°C. Although fla24 cells assemble full-length flagella at 21°C, IFT81 protein localization is dramatically altered. Instead of localizing at the basal body and along the flagella, IFT81 is concentrated at the proximal end of the flagella. The pseudorevertants show wild-type IFT81 localization at 21°C, but proximal end localization of IFT81 at 32°C.

Conclusions

The change in the AAA5 domain of the cytoplasmic dynein in fla24 may block the recycling of IFT trains after retrograde transport. It is clear that different alleles in the flagellar motors reveal different functions and roles. Multiple alleles will be important for understanding structure-function relationships.
Hypoxia: how does the monocyte-macrophage system respond to changes in oxygen availability?
Authors: Strehl Cindy , Fangradt Monique , Fearon Ursula , Gaber Timo , Buttgereit Frank , Veale Douglas J
Published: October 2013

Hypoxia is an important feature of inflamed tissue, such as the RA joint. Activated monocytes/macrophages and endothelial cells play a pivotal role in the pathogenesis of RA, implicated in the mechanism of inflammation and erosion. During development, myeloid progenitor cells sequentially give rise to monoblasts, promonocytes, and monocytes that are released from the bone marrow into the bloodstream. After extravasation, monocytes differentiate into long-lived, tissue-specific macrophages or DCs. The effect of different oxygen concentrations experienced by these cells during maturation represents a novel aspect of this developmental process. In inflamed joint tissue, the microvascular architecture is highly dysregulated; thus, efficiency of oxygen supply to the synovium is poor. Therefore, invading cells must adapt instantaneously to changes in the oxygen level of the microenvironment. Angiogenesis is an early event in the inflammatory joint, which is important in enabling activated monocytes to enter via endothelial cells by active recruitment to expand the synovium into a “pannus”, resulting in cartilage degradation and bone destruction. The increased metabolic turnover of the expanding synovial pannus outpaces the dysfunctional vascular supply, resulting in hypoxia. The abnormal bioenergetics of the microenvironment further promotes synovial cell invasiveness. In RA, joint hypoxia represents a potential threat to cell function and survival. Notably, oxygen availability is a crucial parameter in the cellular energy metabolism, itself an important factor in determining the function of immune cells.
Stress Resilience: A Low-Anxiety Genotype Protects Male Mice From the Consequences of Chronic Psychosocial Stress
Authors: Füchsl Andrea M. , Neumann Inga D. , Reber Stefan O.
Published: October 2013

Chronic psychosocial stress is a risk factor for the development of affective as well as somatic disorders. However, vulnerability to adverse stress effects varies between individuals, with previous negative life events along with genetic predisposition playing a major role. In support, we previously showed that the consequences of chronic psychosocial stress induced by chronic subordinate colony housing (CSC, 19 days) can be amplified by pre-exposing mice to repeated maternal separation during early life. To test the significance of the genetic predisposition on the effects of CSC, mice selectively bred for high (mHAB) and low (mLAB) anxiety-related behavior and nonselected CD1 mice (mNAB) were exposed to CSC in the present study. In confirmation of our previous results, CSC mice of both mHAB and mNAB lines displayed chronic stress-related symptoms including increased adrenal weight, decreased adrenal in vitro ACTH sensitivity, lower plasma corticosterone to ACTH ratio, and increased interferon-γ secretion from isolated mesenteric lymph node cells compared with single-housed controls of the respective line. However, the CSC-induced anxiogenic effect found in mNAB was not confirmed in mHAB mice, possibly due to a ceiling effect in these highly anxious mice. Interestingly, mHAB were not more vulnerable to CSC than mNAB mice, whereas mLAB mice were resilient to CSC as indicated by all of the above mentioned parameters assessed. Taken together, our findings indicate that the genetic predisposition, in this case the innate anxiety of an individual, affects vulnerability to chronic psychosocial stress, with a low-anxiety phenotype mediating resilience to both affective and somatic consequences of CSC.
The Emerging Genomic Landscape of Endometrial Cancer
Authors: Le Gallo Matthieu , Bell Daphne W
Published: October 2013

BACKGROUND

Endometrial cancer is responsible for approximately 74 000 deaths annually among women worldwide. It is a heterogeneous disease comprising multiple histologic subtypes. In the US, the majority of deaths from endometrial carcinoma are attributed to the serous and endometrioid subtypes. An understanding of the fundamental genomic alterations that drive serous and endometrioid endometrial carcinomas lays the foundation for the identification of molecular markers that could improve the clinical management of patients presenting with these tumors.

CONTENT

We review the current state of knowledge regarding somatic genomic alterations that occur in serous and endometrioid endometrial tumors. We present this knowledge in a historical context by reviewing the genomic alterations that studies of individual genes and proteins have identified over the past 2 decades or so. We then review very recent comprehensive and systematic surveys of genomic, exomic, transcriptomic, epigenomic, and proteomic alterations in serous and endometrioid endometrial carcinomas.

The recent mapping of the genomic landscape of serous and endometrioid endometrial carcinomas has produced the first comprehensive molecular classification of these tumors, which has distinguished 4 molecular subgroups: a POLE [polymerase (DNA directed), ε, catalytic subunit] ultramutated subgroup, a hypermutated/microsatellite-unstable subgroup, a copy number–low/microsatellite-stable subgroup, and a copy number–high subgroup. This molecular classification may ultimately serve to refine the diagnosis and treatment of women with endometrioid and serous endometrial tumors.
Embodied musicality: Nietzsche, Grotowski and musicalized processes in theatre making
Authors: Frendo Mario
Published: October 2013

Since the 1960s research in theatre laboratories on the nature of acting and structures of performance has dilated the possibilities of the theatrical event. One of the direct outcomes of these developments is the musicalization of theatrical performance. Although relatively recent, the focus on musicality in theatre echoes interests of visionaries and thinkers since at least the turn of the twentieth century. This article discusses Jerzy Grotowski’s musicalized processes in his theatre making. I will argue that Grotowski’s praxis resonates earlier claims made by Friedrich Nietzsche that tragedy, representing as it were a genesis of western theatre practice, was born out of the spirit of music. I will propose that rather than bridging the boundaries of music and theatre, Grotowski promotes music as an intrinsic element in theatre through the embodied musicality of the performer.
Citing musicality: Performance knowledge in the Gardzienice archive
Authors: Spatz Ben
Published: October 2013

This article draws on previously published multimedia documents to explore the notion of musicality in the work of Wodzimierz Staniewski and the Gardzienice Centre for Theatre Practices. In addition to offering a close analysis of several documented moments – including performances, work demonstrations, expeditions and gatherings – it tests the ability of multimedia documentation to capture performance knowledge, arguing that the work of Gardzienice is a paradigmatic example of ‘practice as research’. Taking the archive as a crucial dimension of the dissemination of knowledge, the article uses multimedia citation to examine the specific contributions of Gardzienice in the context of musicality as a relation between the theatrical and the musical. The article demonstrates that the stability of the archive allows for a detailed explication of performance knowledge in a way that is not possible from live performance alone.
The craft of making art: The creative processes of eight musical theatre songwriters
Authors: Horowitz Mark Eden
Published: October 2013

This article offers an examination of the creative process as revealed in the papers of eight musical theatre songwriters, seven of whose collections are in the Music Division of the Library of Congress: Jerome Kern, Irving Berlin, Oscar Hammerstein II, Cole Porter, Richard Rodgers, Leonard Bernstein, Stephen Sondheim and Jonathan Larson.
Encoding of Prospective Tasks in the Human Prefrontal Cortex under Varying Task Loads
Authors: Momennejad Ida , Haynes John-Dylan
Published: October 2013

Successful realization of planned actions requires the brain to encode intentions over delays. Previous research has indicated that several regions in the rostral or anterior prefrontal cortex (PFC) encode delayed intentions. However, different processes may encode the same future task depending on task load during the delay. This difference may depend on the computational resources available when the delay is occupied with an ongoing task and when it is task-free. Here we directly investigated and compared the representation of delayed intentions in the human brain in the presence and absence of ongoing task load during the delay. We acquired fMRI data in combination with an event-based prospective memory design where human subjects remembered to perform the same future tasks over occupied and task-free delays. We used time-resolved multivoxel pattern classification and found that: (1) rostrolateral PFC (BA 46) encoded the delayed intention during both delay types; (2) rostromedial PFC (BA 10) encoded the intentions during occupied delays; whereas (3) a variety of more posterior regions, including the anterior cingulate cortex (BA 24), the supplementary motor area (BA 6), and the precuneus, encoded intentions during task-free delays. Overall, the medial PFC encoded delayed intentions more rostrally in the presence of an ongoing delay task and more caudally in its absence. Thus, rostromedial PFC may play a specialized role in the encoding of prospective memory that depends on higher computational demands (e.g., given higher task load during the delay). In contrast, the rostrolateral PFC is a more general area that encodes future intentions regardless of task load.
CXC Chemokine Receptor 7 (CXCR7) Affects the Migration of GnRH Neurons by Regulating CXCL12 Availability
Authors: Memi Fani , Abe Philipp , Cariboni Anna , MacKay Fabienne , Parnavelas John G. , Stumm Ralf
Published: October 2013

Gonadotropin-releasing hormone (GnRH) neurons are neuroendocrine cells, located in the hypothalamus, that play an essential role in mammalian reproduction. These neurons originate in the nasal placode and migrate during embryonic development, in association with olfactory/vomeronasal nerves, first in the nose, then through the cribriform plate to enter the forebrain, before settling in the hypothalamus. One of the molecules required for their early migration in the nose is the chemokine CXCL12, which is expressed in the embryonic nasal mesenchyme in an increasing ventral to dorsal gradient, presumably guiding GnRH neurons toward the forebrain. Mice lacking CXCR4, the receptor for CXCL12, exhibit defective GnRH cell movement and a significant reduction in their number, suggesting that CXCL12/CXCR4 signaling is important in the migration and survival of these neurons. Here, we investigated the role of the more recently identified second CXCL12 receptor, CXCR7, in GnRH neuron development. We demonstrate that CXCR7 is expressed along the migratory path of GnRH neurons in the nasal cavity and, although not expressed by GnRH neurons, it affects their migration as indicated by the ectopic accumulation of these cells in the nasal compartment inCXCR7−/−mice. Absence of CXCR7 caused abnormal accumulation of CXCL12-RFP at CXCR4-positive sites in the nasal area of CXCL12-RFP-transgenic mice and excessive CXCL12-dependent intracellular clustering of CXCR4 in GnRH neurons, suggesting internalization. These findings imply that CXCR7 regulates CXCL12 availability by acting as a scavenger along the migratory path of GnRH neurons and, thus, influences the migration of these cells in a noncell-autonomous manner.
State-Dependent Effects of Transcranial Oscillatory Currents on the Motor System: What You Think Matters
Authors: Feurra Matteo , Pasqualetti Patrizio , Bianco Giovanni , Santarnecchi Emiliano , Rossi Alessandro , Rossi Simone
Published: October 2013

Imperceptible transcranial alternating current stimulation (tACS) changes the endogenous cortical oscillatory activity in a frequency-specific manner. In the human motor system, tACS coincident with the idling beta rhythm of the quiescent motor cortex increased the corticospinal output. We reasoned that changing the initial state of the brain (i.e., from quiescence to a motor imagery task that desynchronizes the local beta rhythm) might also change the susceptibility of the corticospinal system to resonance effects induced by beta-tACS. We tested this hypothesis by delivering tACS at different frequencies (theta, alpha, beta, and gamma) on the primary motor cortex at rest and during motor imagery. Motor-evoked potentials (MEPs) were obtained by transcranial magnetic stimulation (TMS) on the primary motor cortex with an online-navigated TMS–tACS setting. During motor imagery, the increase of corticospinal excitability was maximal with theta-tACS, likely reflecting a reinforcement of working memory processes required to mentally process and “execute” the cognitive task. As expected, the maximal MEPs increase with subjects at rest was instead obtained with beta-tACS, substantiating previous evidence. This dissociation provides new evidence of state and frequency dependency of tACS effects on the motor system and helps discern the functional role of different oscillatory frequencies of this brain region. These findings may be relevant for rehabilitative neuromodulatory interventions.
Titration of GLI3 Repressor Activity by Sonic Hedgehog Signaling Is Critical for Maintaining Multiple Adult Neural Stem Cell and Astrocyte Functions
Authors: Petrova Ralitsa , Garcia A. Denise R. , Joyner Alexandra L.
Published: October 2013

Sonic hedgehog (SHH), a key regulator of embryonic neurogenesis, signals directly to neural stem cells (NSCs) in the subventricular zone (SVZ) and to astrocytes in the adult mouse forebrain. The specific mechanism by which the GLI2 and GLI3 transcriptional activators (GLI2Aand GLI3A) and repressors (GLI2Rand GLI3R) carry out SHH signaling has not been addressed. We found that the majority of slow-cycling NSCs expressGli2andGli3,whereasGli1is restricted ventrally and all three genes are downregulated when NSCs transition into proliferating progenitors. Surprisingly, whereas conditional ablation ofSmoin postnatal glial fibrillary acidic protein-expressing cells results in cell-autonomous loss of NSCs and a progressive reduction in SVZ proliferation, without an increase in glial cell production, removal ofGli2orGli3does not alter adult SVZ neurogenesis. Significantly, removingGli3inSmoconditional mutants largely rescues neurogenesis and, conversely, expression of a constitutive GLI3Rin the absence of normalGli2andGli3abrogates neurogenesis. Thus unattenuated GLI3Ris a primary inhibitor of adult SVZ NSC function. Ablation ofGli2andGli3revealed a minor role for GLI2Rand little requirement for GLIAfunction in stimulating SVZ neurogenesis. Moreover, we found that similar rules of GLI activity apply to SHH signaling in regulating SVZ-derived olfactory bulb interneurons and maintaining cortical astrocyte function. Namely, fewer superficial olfactory bulb interneurons are generated in the absence ofGli2andGli3, whereas astrocyte partial gliosis results from an increase in GLI3R. Thus precise titration of GLIRlevels by SHH is critical to multiple functions of adult NSCs and astrocytes.
Kalman Filtering Naturally Accounts for Visually Guided and Predictive Smooth Pursuit Dynamics
Authors: Orban de Xivry Jean-Jacques , Coppe Sébastien , Blohm Gunnar , Lefèvre Philippe
Published: October 2013

The brain makes use of noisy sensory inputs to produce eye, head, or arm motion. In most instances, the brain combines this sensory information with predictions about future events. Here, we propose that Kalman filtering can account for the dynamics of both visually guided and predictive motor behaviors within one simple unifying mechanism. Our model relies on two Kalman filters: (1) one processing visual information about retinal input; and (2) one maintaining a dynamic internal memory of target motion. The outputs of both Kalman filters are then combined in a statistically optimal manner, i.e., weighted with respect to their reliability. The model was tested on data from several smooth pursuit experiments and reproduced all major characteristics of visually guided and predictive smooth pursuit. This contrasts with the common belief that anticipatory pursuit, pursuit maintenance during target blanking, and zero-lag pursuit of sinusoidally moving targets all result from different control systems. This is the first instance of a model integrating all aspects of pursuit dynamics within one coherent and simple model and without switching between different parallel mechanisms. Our model suggests that the brain circuitry generating a pursuit command might be simpler than previously believed and only implement the functional equivalents of two Kalman filters whose outputs are optimally combined. It provides a general framework of how the brain can combine continuous sensory information with a dynamic internal memory and transform it into motor commands.