bluuebunny/crossref_metadata_2025 huggingface dataset:
Cause, Care, Cure: Research Priorities for Alzheimer’s Disease and Related Dementias
Authors: Stolee Paul , Hillier Loretta M. , Cook Sheila , Rockwood Kenneth
Published: November 2011

Une partie de la stratégie de l’Ontario sur la maladie d’Alzheimer et les démences connexes (MADC) était de développer les priorités de recherche et de recommander des stratégies pour le renforcement des capacités de recherche. Le processus adopté pour atteindre ces objectifs comprenaient une analyse de l’environnement, des entretiens avec les informateurs clés, des enquêtes et un atelier de consensus ; ce processus a impliqué plus de 100 chercheurs, cliniciens, les personnes atteintes de démence précoce, et les aidants membres de familles. Ce document décrit le processus entrepris, les principaux problèmes identifiés et les recommandations pour les priorités de recherche et de renforcement des capacités de recherche ; il fournit également une orientation stratégique pour la recherche sur la démence en Ontario qui est pertinente pour d’autres juridictions. La recherche MADC dans tous ses aspects est nécessaire pour faire progresser la connaissance des causes de la démence, les soins et la guérison ; des lacunes existent actuellement dans la compréhension des approches efficaces pour les soins et le transfert des connaissances. La capacité pour la recherche de haut calibre reste sur le maintien de plans de carrière attractifs pour les chercheurs, des infrastructures solides et de partenariats forts. Afin que la recherche informera les politiques et pratiques, de meilleurs mécanismes seront nécessaires pour l’échange de connaissances.
Increasing incidence of invasive pneumococcal disease and pneumonia despite improved vaccination uptake: surveillance in Hull and East Yorkshire, UK, 2002–2009
Authors: ELSTON J. W. T. , SANTANIELLO-NEWTON A. , MEIGH J. A. , HARMER D. , ALLGAR V. , ALLISON T. , RICHARDSON G. , MEIGH R. , PALMER S. R. , BARLOW G.
Published: November 2011

Introduction of pneumococcal polysaccharide (PPV23) and conjugate vaccine (PCV7) programmes were expected to change the epidemiology of invasive pneumococcal disease (IPD) and pneumonia in the UK. We describe the epidemiology of IPD and hospitalization with pneumonia using high-quality surveillance data over an 8-year period, 2002–2009. Although PPV23 uptake increased from 49% to 70% and PCV7 uptake reached 98% by 2009, the overall incidence of IPD increased from 11·8/100 000 to 16·4/100 000 (P=0·13), and the incidence of hospitalization with pneumonia increased from 143/100 000 to 207/100 000 (P<0·001). Although a reduction in the proportion of IPD caused by PCV7 serotypes was observed, concurrent increases in PPV23 and non-vaccine serotype IPD contributed to an increased IPD burden overall. Marked inequalities in the geographical distribution of disease were observed. Existing vaccination programmes have, so far, not been sufficient to address an increasing burden of pneumococcal disease in our locality.
Recent trends in the epidemiology of non-typhoidalSalmonellain Israel, 1999–2009
Authors: BASSAL R. , REISFELD A. , ANDORN N. , YISHAI R. , NISSAN I. , AGMON V. , PELED N. , BLOCK C. , KELLER N. , KENES Y. , TARAN D. , SCHEMBERG B. , KEN-DROR S. , ROUACH T. , CITRON B. , BERMAN E. , GREEN M. S. , SHOHAT T. , COHEN D.
Published: November 2011

The aim of the present study was to assess the recent trends in the epidemiology of non-typhoidSalmonellain Israel using a sentinel laboratory-based surveillance network. Between 1999 and 2009, 8758Salmonellastool isolates were reported by five sentinel laboratories. There was a significant decrease in the incidence rate ofSalmonellaisolates from 70·5/100 000 in 1999 to 21·6/100 000 in 2005 followed by a slight increase to 30·3/100 000 in 2009. Of allSalmonella, 64·3% were isolated from children in the 0–4 years age group. Up to 2008,S. Enteritidis was the most prevalent serotype and in 2009S. Infantis emerged as the most commonSalmonellaserotype. The decrease in the incidence ofS. Enteritidis andS. Typhimurium and increase inS. Infantis among humans were associated with a similar trend among breeding flocks, which followed significant preventive interventions conducted againstS. Enteritidis andS. Typhimurium infections in poultry. Tight surveillance and education of food handlers and consumers should be enhanced to reduce the foodborne transmission ofSalmonellain Israel.
Towards new therapeutic approaches for malignant melanoma
Authors: Pacheco Ivan , Buzea Cristina , Tron Victor
Published: November 2011

Recent progress in understanding the molecular mechanisms of the initiation and progression of melanoma has created new opportunities for developing novel therapeutic modalities to manage this potentially lethal disease. Although at first glance, melanoma carcinogenesis appears to be a chaotic system, it is indeed, arguably, a deterministic multistep process involving sequential alterations of proto-oncogenes, tumour suppressors and miRNA genes. The scope of this article is to discuss the most recent and significant advances in melanoma molecular therapeutics. It is apparent that using single agents targeting solely individual melanoma pathways might be insufficient for long-term survival. However, the outstanding results on melanoma survival observed with novel selective inhibitors of B-RAF, such as PLX4032 give hope that melanoma can be cured. The fact that melanoma develops acquired resistance to PLX4032 emphasises the importance of simultaneously targeting several pathways. Because the most striking feature of melanoma is its unsurpassed ability to metastasise, it is important to implement newer systems for drug delivery adapted from research on stem cells and nanotechnology.
Finding similar/diverse solutions in answer set programming
Authors: EITER THOMAS , ERDEM ESRA , ERDOGAN HALIT , FINK MICHAEL
Published: November 2011

For some computational problems (e.g., product configuration, planning, diagnosis, query answering, phylogeny reconstruction), computing a set of similar/diverse solutions may be desirable for better decision-making. With this motivation, we have studied several decision/optimization versions of this problem in the context of Answer set programming (ASP), analyzed their computational complexity, and introduced offline/online methods to compute similar/diverse solutions of such computational problems with respect to a given distance function. All these methods rely on the idea of computing solutions to a problem by means of finding the answer sets for an ASP program that describes the problem. The offline methods compute all solutions of a problem in advance using the ASP formulation of the problem with an existing ASP solver, like clasp, and then identify similar/diverse solutions using some clustering methods (possibly in ASP as well). The online methods compute similar/diverse solutions of a problem following one of the three approaches: by reformulating the ASP representation of the problem to compute similar/diverse solutions at once using an existing ASP solver; by computing similar/diverse solutions iteratively (one after the other) using an existing ASP solver; by modifying the search algorithm of an ASP solver to compute similar/diverse solutions incrementally. All these methods are sound; the offline method and the first online method are complete whereas the others are not. We have modified clasp to implement the last online method and called it clasp-nk. In the first two online methods, the given distance function is represented in ASP; in the last one, however, it is implemented in C++. We have shown the applicability and the effectiveness of these methods using clasp or clasp-nk on two sorts of problems with different distance measures: on a real-world problem in phylogenetics (i.e., reconstruction of similar/diverse phylogenies for Indo-European languages), and on several planning problems in a well-known domain (i.e., Blocks World). We have observed that in terms of computational efficiency (both time and space), the last online method outperforms the others; also, it allows us to compute similar/diverse solutions when the distance function cannot be represented in ASP (e.g., due to some mathematical functions not supported by the ASP solvers) but can be easily implemented in C++.
Standing for Women? Which Women? The Substantive Representation of Women's Interests and the Research Imperative of Intersectionality
Authors: Smooth Wendy
Published: November 2011

In conducting interviews with female African American state legislators, I found that the great debates among women and politics scholars over the meaning of women's issues have not captured a major issue that surfaced time and again in the interviews. The African American women I interviewed affirmed that “women's issues” constituted a top priority on their legislative agendas and understood themselves as representatives of women's interests. But when they began to discuss the issues they championed on behalf of women, these issues were not the “usual suspects.” They often mentioned proposed legislation that I would have coded as a “children's issue” or, at times, a “race issue.” These legislators articulated a political agenda reflecting crosscutting issues that were not easily codified along a single issue axis. Instead, the legislators articulated their legislative priorities as complex and multifaceted. They saw their legislative priorities affecting constituents across their districts, but they also keenly expressed the impact of these issues on the lives and well-being of women in particular.
Women as Candidates: An Experimental Study in Turkey
Authors: Matland Richard E. , Tezcür Güneş Murat
Published: November 2011

Patriarchal practices and understandings, especially those based on religious teachings, are seen as serious hindrances to women's access to political power. This obstacle often is seen as greatest in countries where Islam is the dominant religion. This study offers preliminary insights regarding how the sex of political candidates affects voting perceptions and behavior in Turkey, one of the few democratic countries with a Muslim majority population. We designed an experiment in which university students read speeches by candidates from the two major parties (AKP and CHP), randomly varying the sex of the candidates. We find that candidate sex influences respondents' evaluations of areas of competence and perceptions of individual characteristics. It has almost no impact, however, on voting decisions. When it comes to voting, party support and policy stands are vastly more important than candidate sex, even for religiously observant voters.
Gender and “Peace Work”: An Unofficial History of Israeli-Palestinian Peace Negotiations
Authors: Aharoni Sarai
Published: November 2011

Unlike earlier attempts to theorize Israeli women's peace activism in civil society, this article examines the involvement of women in backstage roles of formal negotiations during the Oslo Process. On the basis of a qualitative analysis of the organizational structure and gender division of labor in Israeli negotiating bodies, I find that women were placed as midlevel negotiators and professional and legal advisors, and also served as spokeswomen and secretaries. This pattern of participation reveals 1) that the “security logic,” developed by Israeli negotiators led to, and reinforced, a structured gendered division of labor, providing a rational justification for gender inequality; 2) that the ability to control administrative capacities and women workers generated symbolic masculine power and assisted in maintaining asymmetries between Israeli and Palestinian delegations; 3) and that midlevel Israeli negotiators' narratives reveal the extent to which conceptual confusion and self-contradictory approaches toward the Oslo Accords reinforced women's overall invisibility. I conclude that patterns of rigid gender roles in official negotiating structures not only minimize women's meaningful inclusion in peace negotiations but also affect the production of public historical narratives about gender, peace, and war.
Patriarchal Policing of Sex in the Early United States
Authors: Kann Mark E.
Published: November 2011

On the eve of the American Revolution, Benjamin Franklin published a satire instructing the British on humbling their American vassals. The British could castrate American males, thereby reducing American population growth. The logistics were simple: “Let a company of sow-gelders, consisting of 100 men, accompany the army. On their arrival at any town or village, let orders be given that on their blowing of the horn all the males be assembled in the market place. If the corps are men of skill and ability in their profession, they will make great dispatch, and retard but very little the progress of the army” (Franklin 1987, 718). Satire aside, Franklin's generation believed that sex and reproduction had a significant impact on the independence, strength, and durability of nations.
CEDAR Electrodynamics Thermosphere Ionosphere (ETI) Challenge for systematic assessment of ionosphere/thermosphere models: NmF2, hmF2, and vertical drift using ground‐based observations
Authors: Shim J. S. , Kuznetsova M. , Rastätter L. , Hesse M. , Bilitza D. , Butala M. , Codrescu M. , Emery B. , Foster B. , Fuller‐Rowell T. , Huba J. , Mannucci A. J. , Pi X. , Ridley A. , Scherliess L. , Schunk R. W. , Stephens P. , Thompson D. C. , Zhu L. , Anderson D. , Chau J. L. , Sojka J. J. , Rideout B.
Published: November 2011

Objective quantification of model performance based on metrics helps us evaluate the current state of space physics modeling capability, address differences among various modeling approaches, and track model improvements over time. The Coupling, Energetics, and Dynamics of Atmospheric Regions (CEDAR) Electrodynamics Thermosphere Ionosphere (ETI) Challenge was initiated in 2009 to assess accuracy of various ionosphere/thermosphere models in reproducing ionosphere and thermosphere parameters. A total of nine events and five physical parameters were selected to compare between model outputs and observations. The nine events included two strong and one moderate geomagnetic storm events from GEM Challenge events and three moderate storms and three quiet periods from the first half of the International Polar Year (IPY) campaign, which lasted for 2 years, from March 2007 to March 2009. The five physical parameters selected were NmF2 and hmF2 from ISRs and LEO satellites such as CHAMP and COSMIC, vertical drifts at Jicamarca, and electron and neutral densities along the track of the CHAMP satellite. For this study, four different metrics and up to 10 models were used. In this paper, we focus on preliminary results of the study using ground‐based measurements, which include NmF2 and hmF2 from Incoherent Scatter Radars (ISRs), and vertical drifts at Jicamarca. The results show that the model performance strongly depends on the type of metrics used, and thus no model is ranked top for all used metrics. The analysis further indicates that performance of the model also varies with latitude and geomagnetic activity level.
Field experimental approach to bromide leaching as affected by scale‐specific rainfall characteristics
Authors: Wendroth Ole , Vasquez Vicente , Matocha Christopher J.
Published: November 2011

Although inherent soil spatial and temporal variabilities complicate analysis of solute leaching, impacts of specific processes associated with rainfall amount, intensity, and frequency on solute leaching under field conditions require investigation. The objective of this study was to introduce (1) a new experimental approach to quantify bromide (Br−) leaching under field conditions as influenced by rainfall characteristics and (2) analytical opportunities applicable to scale‐specific spatial treatment distribution. The quantitative range of treatments was established in nonrandom periodically oscillating patterns. The characteristic length of a period over which a treatment fluctuates was considered the specific treatment scale. A Br−tracer study was established in the field with treatments applied at two different spatial scales. The tracer was applied with a sprayer in a transect of 32 plots, each 2 m long, followed by a site‐specific sprinkler irrigation, and 128 soil cores subsequently taken at 0.5 m intervals and divided into 10‐cm depth increments. The scale‐specific associations between treatments and Br−center of mass (COM) were addressed. Treatments can be periodically imposed over specific scales and their spatial relationships quantified with semivariance and power spectral analysis. An additive state‐space model was applied to separate the long‐ and short‐wave components of Br−COM. Subsequently, the large‐scale process was described in an autoregressive state‐space model. The proposed experimental approach and the separation of small‐ and large‐scale variability components support studying soil ecosystem processes that vary at different scales even in the presence of underlying large‐scale trends that are currently considered obstacles in field research.
A Qualitative Study of Interference With Communicative Participation Across Communication Disorders in Adults
Authors: Baylor Carolyn , Burns Michael , Eadie Tanya , Britton Deanna , Yorkston Kathryn
Published: November 2011

Purpose

To explore the similarities and differences in self-reported restrictions in communicative participation across different communication disorders in community-dwelling adults.

Method

Interviews were conducted with 44 adults representing 7 different medical conditions: spasmodic dysphonia, multiple sclerosis, stroke, stuttering, Parkinson’s disease, amyotrophic lateral sclerosis, and laryngectomy. This article represents a secondary analysis of qualitative data collected in cognitive interviews during development of the Communicative Participation Item Bank. The data were analyzed to identify themes in participants' experiences related to communicative participation.

Results

Participants described many situations in which they experienced interference in communicative participation. Two themes emerged from the data. The first theme was
Interference is both “functional” and “emotional,”
in which participants defined interference as limitations in accomplishing tasks and emotional consequences. The second theme was
“It depends”—sources of interference,
in which participants described many variables that contribute to interference in participation. Participants had limited control of some variables such as symptoms and environmental contexts, but personal decisions and priorities also influenced participation.

Conclusions

Despite different impairments and activity limitations, participants described similar communicative participation restrictions. These similarities may have theoretical and clinical implications in terms of how we assess, treat, and study the participation restrictions associated with communication disorders.
Language in the Cerebellum
Authors: Highnam Clifford L. , Bleile Ken M.
Published: November 2011

Purpose

To explore increasingly compelling evidence that the adult human cerebellum is involved in nonmotor affective and cognitive activity, including language—functions that have in the past been associated largely with the limbic system and the cerebral cortex.

Method

We review clinical studies of patients with cerebellar lesions, nonclinical neuroimaging studies of individuals engaged in completing selected tasks, and neuroanatomical as well as neuroimaging studies of brain interconnections. In the course of this review, we also report on a variety of hypotheses regarding the nature of the cerebellum’s work in affective processing and language/cognition.

Results

This review suggests that the cerebellum has considerable influence in language processing and other related higher level affective/cognitive activities.

Conclusion

We conclude with a preliminary list of important clinical implications of these results.
The Utility of Pitch Elevation in the Evaluation of Oropharyngeal Dysphagia: Preliminary Findings
Authors: Malandraki Georgia A. , Hind Jacqueline A. , Gangnon Ronald , Logemann Jeri A. , Robbins JoAnne
Published: November 2011

Purpose

To evaluate the utility of a pitch elevation task in the assessment of oropharyngeal dysphagia.

Method

This study was a pilot prospective cohort study including 40 consecutive patients (16 male and 24 female) who were referred by their physician for a swallowing evaluation. Patients were evaluated with a noninstrumental clinical examination and a videofluoroscopic swallow study, and participated in a pitch elevation task during videofluoroscopic image acquisition. Relationships between pitch elevation measurements (acoustic and perceptual) and swallow parameters (penetration/aspiration and residue) were investigated.

Results

Results of this pilot study revealed that both maximum fundamental frequency (F
0
) and perceptual evaluation of pitch elevation independently significantly predicted Penetration-Aspiration Scale scores for thin liquid swallows (
p
= .01 and .03, respectively). Vocal range (average pitch to falsetto) was not sensitive in predicting likelihood of oropharyngeal dysphagia.

Conclusions

Findings indicate that reduced pitch elevation can be indicative of reduced airway protection and swallowing impairment in some dysphagia patients and may be a useful supplement to dysphagia screening and diagnosis. Further investigation is warranted to determine the optimal utility of this procedure for different diagnostic categories of patients.
Coping Strategies and Adolescents: Learning to Take Care of Self and Stuttering during Treatment
Authors: Blood Gordon W. , Blood Ingrid M. , Dorward Sarah , Boyle Michael P. , Tramontana G. Michael
Published: November 2011

The purpose of this paper is to describe coping in the context of adolescence and stuttering. Adolescents who stutter are a unique group of individuals dealing with an episodic, variable, and chronic disorder during a critical developmental stage in their lives. We provide a brief review of adolescence, coping constructs, coping during adolescence, and coping programs. We highlight the role of the speech-language pathologist is as an advocate/guide assisting adolescents who stutter develop appropriate, adaptive strategies for dealing with everyday stressors and the added potential stress associated with stuttering.
The Advancement of Neuroimaging Research Investigating Developmental Stuttering
Authors: Beal Deryk S.
Published: November 2011

We are amassing information about the role of the brain in speech production and the potential neural limitations that coincide with developmental stuttering at a fast rate. As such, it is difficult for many clinician-scientists who are interested in the neural correlates of stuttering to stay informed of the current state of the field. In this paper, I aim to inspire clinician-scientists to tackle hypothesis-driven research that is grounded in neurobiological theory. To this end, I will review the neuroanatomical structures, and their functions, which are implicated in speech production and then describe the relevant differences identified in these structures in people who stutter relative to their fluently speaking peers. I will conclude the paper with suggestions on directions of future research to facilitate the evolution of the field of neuroimaging of stuttering.
The Art of Transparency
Authors: Sayim Bilge , Cavanagh Patrick
Published: November 2011

Artists throughout the ages have discovered a number of techniques to depict transparency. With only a few exceptions, these techniques follow closely the properties of physical transparency. The two best known properties are X-junctions and the luminance relations described by Metelli. X-junctions are seen where the contours of a transparent material cross contours of the surface behind; Metelli's constraints on the luminance relations between the direct and filtered portions of the surface specify a range of luminance values that are consistent with transparency. These principles have been used by artists since the time of ancient Egypt. However, artists also discovered that stimuli can be seen as transparent even when these physical constraints are not met. Ancient Greek artists, for example, were able to depict transparent materials in simple black-and-white line drawings. Artists also learned how to represent transparency in cases where neither X-junctions nor Metelli's constraints could apply: for example, where no portions of the objects behind the transparent material extend beyond it. Many painters convincingly portrayed transparency in these cases by depicting the effects the transparent medium would have on material or object properties. Here, we show how artists employed these and other techniques revealing their anticipation of current formalizations of perceived transparency, and we suggest new, as-yet-untested principles.
High-resolution Spectroscopy and Spectropolarimetry of Some Late F- / Early G-type Sun-like Stars as Targets for Zeeman Doppler Imaging
Authors: Waite I. A. , Marsden S. C. , Carter B. D. , Alécian E. , Brown C. , Burton D. , Hart R.
Published: November 2011

High-resolution spectroscopy and spectropolarimetry have been undertaken at the Anglo-Australian Telescope in order to identify suitable targets for magnetic studies of young Sun-like stars, for the proxy study of early solar evolution. This study involved the investigation of some variable late F- / early G-type Sun-like stars originally identified by the Hipparcos mission. Of the 38 stars observed for this study, HIP 31021, HIP 64732, HIP 73780 were found to be spectroscopic binary stars, while HIP 19072, HIP 67651 and HIP 75636 are also likely to be binaries and HIP 33111 could even be a triple system. Magnetic fields were detected on a number of the survey stars: HIP 21632, HIP 43720, HIP 48770, HIP 62517, HIP 71933, HIP 77144, HIP 89829, HIP 90899 and HIP 105388, making these stars good candidates for follow-up Zeeman Doppler imaging studies.
Spencer Smith-White 1909 - 1998
Authors: Peacock Jim , Barlow Bryan , Carolin Roger
Published: November 2011

Spencer Smith-White's research group at the University of Sydney was for many years the foremost laboratory studying the cytology, cytogenetics and cytoevolution of the Australian flora. He pioneered this field with his chromosomal studies on major Australian families, such as the Rutaceae, Myrtaceae, Proteaceae and Epacridaceae. His cytogenetic analyses underpinned his discussions of the origins and distribution of the major elements of the Australian flora.
Contrasting behavioural responses of grazing mayflies and detritivorous caddisflies to predatory fish
Authors: Boyero Luz , Rincón Pedro A. , Bosch Jaime
Published: November 2011

Invertebrates living in streams where predatory fish are present are often able to detect them through water-borne chemical cues and respond with behavioural changes that lower predation risk. We hypothesised that behavioural responses to a predatory fish (brown trout, Salmo trutta) would be stronger in grazing mayflies (Baetis sp. and Epeorus sp.) than in detritivorous caddisflies (Potamophylax latipennis and Chaetopteryx sp.) in a montane stream in central Spain, because of differences in their foraging ecology and the presence of a protective case in the latter. Grazing mayflies reduced their rates of movement and entrance into the drift when trout were present, but this response disappeared shortly after trout removal by electrofishing. Mayflies also showed marked drift diel periodicity when trout were present. In contrast, detritivorous caddisflies responded to the potential predation threat by withdrawing into their case. However, their response was the same regardless of the presence of trout, which also had no influence on their movement patterns or drift activity. Our results suggest that effects of predatory fish on stream invertebrates vary with invertebrate traits such as foraging ecology and predator-avoidance strategies.
A multi-faceted approach for quantifying the estuarine - nearshore transition in the life cycle of the bull shark, Carcharhinus leucas
Authors: Werry J. M. , Lee S. Y. , Otway N. M. , Hu Y. , Sumpton W.
Published: November 2011

Understanding the ontogenetic habitat linkages of sharks is important for conservation and managing human interactions. We used acoustic telemetry, catch data, elemental and stable isotope signatures and dietary analyses to investigate ontogenetic habitat use in south-east Queensland, Australia, by the bull shark Carcharhinus leucas, a IUCN ‘near-threatened’ species that is implicated in many shark attacks on humans in urban estuaries. Sequential analyses for δ15N and δ13C of vertebrae from five adult C. leucas and laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) for elemental composition from 23 C. leucas, including a pregnant female, were also used to trace ontogenetic habitat dependence. Acoustic telemetry indicated large juvenile and subadult C. leucas remained in estuarine habitats. δ15N values across shark vertebrae showed an ontogenetic shift in diet with total length (TL), confirmed by stomach contents. LA-ICPMS data reflected the ontogenetic movements of C. leucas from natal habitats. Differences among adults were gender related. Shifts in habitat use by subadults were correlated with a sigmoidal δ13C relationship with TL. C. leucas have a multipartite, stage-specific dependency in their transition between habitats along the freshwater–estuarine–marine continuum, making them particularly susceptible to the habitat alteration that is occurring globally.
Booroola BMPR1B mutation alters early follicular development and oocyte ultrastructure in sheep
Authors: Reader Karen L. , Haydon Lisa J. , Littlejohn Roger P. , Juengel Jennifer L. , McNatty Kenneth P.
Published: November 2011

Booroola ewes homozygous (BB) for a mutation in the bone morphogenetic protein receptor-1b (BMPR1B) gene exhibit higher ovulation rates, have larger diameter oocytes at earlier stages of follicular development (i.e. Type 3) and smaller diameter follicles at ovulation than wild-type (++) sheep. However, it is not known when BMPR1B is first expressed in the developing ovary or the cell types involved. In addition, the effects of the BMPR1B mutation on primordial (Type 1) follicles or during growth to the Type 3 stage are unknown. In the present study, BB and ++ fetal ovaries at Days 30–135 of gestation were screened by in situ hybridisation for BMPR1B mRNA. Ovaries from BB and ++ lambs were examined by microscopy to measure follicular and oocyte ultrastructural characteristics in Type 1–3 follicles. BMPR1B mRNA was observed in ovaries from Day 35 of gestation and was evident in oocytes of newly forming and fully formed Type 1 follicles. In BB animals, the Type 1 follicles had larger mean follicular and oocyte diameters, a greater volume of mitochondria, smooth endoplasmic reticulum and ribosomes and a greater surface area of junctions with the granulosa cells compared with ++ animals. It is concluded that the BMPR1B mutation alters follicular development from the onset of follicular formation.
Glycosaminoglycans in the accessory sex glands, testes and seminal plasma of alpaca and ram
Authors: Kershaw-Young Claire M. , Evans G. , Maxwell W. M. C.
Published: November 2011

The viscous nature of alpaca semen limits its use in cryopreservation and other assisted reproductive technologies. The cause and source of this viscosity is unknown although it has been postulated, but never proven, that glycosaminoglycans (GAGs) secreted by the bulbourethral gland are responsible. The present study investigated the concentration and composition of GAGs in alpaca seminal plasma, testes, bulbourethral gland and prostate gland and compared them to those in the ram to determine the relationship between seminal plasma GAGs and viscosity and to identify the source of seminal plasma GAGs. Alpaca seminal plasma contained more GAGs than ram (P < 0.001) and the predominant GAG, keratan sulfate, was correlated with viscosity (P = 0.05, R2 = 0.2635). The alpaca bulbourethral gland contained most GAGs compared with prostate or testis (P < 0.001). In the ram, the prostate contained most GAGs. These findings suggest that GAGs, particularly keratan sulfate, may be the cause of seminal plasma viscosity in alpacas, and that the seminal plasma GAGs originate from the bulbourethral gland.
Bayesian modeling to unmask and predict influenza A/H1N1pdm dynamics in London
Authors: Birrell Paul J. , Ketsetzis Georgios , Gay Nigel J. , Cooper Ben S. , Presanis Anne M. , Harris Ross J. , Charlett André , Zhang Xu-Sheng , White Peter J. , Pebody Richard G. , De Angelis Daniela
Published: November 2011

The tracking and projection of emerging epidemics is hindered by the disconnect between apparent epidemic dynamics, discernible from noisy and incomplete surveillance data, and the underlying, imperfectly observed, system. Behavior changes compound this, altering both true dynamics and reporting patterns, particularly for diseases with nonspecific symptoms, such as influenza. We disentangle these effects to unravel the hidden dynamics of the 2009 influenza A/H1N1pdm pandemic in London, where surveillance suggests an unusual dominant peak in the summer. We embed an age-structured model into a Bayesian synthesis of multiple evidence sources to reveal substantial changes in contact patterns and health-seeking behavior throughout the epidemic, uncovering two similar infection waves, despite large differences in the reported levels of disease. We show how this approach, which allows for real-time learning about model parameters as the epidemic progresses, is also able to provide a sequence of nested projections that are capable of accurately reflecting the epidemic evolution.
Hyperpolarized
13
C dehydroascorbate as an endogenous redox sensor for in vivo metabolic imaging
Authors: Keshari Kayvan R. , Kurhanewicz John , Bok Robert , Larson Peder E. Z. , Vigneron Daniel B. , Wilson David M.
Published: November 2011

Reduction and oxidation (redox) chemistry is involved in both normal and abnormal cellular function, in processes as diverse as circadian rhythms and neurotransmission. Intracellular redox is maintained by coupled reactions involving NADPH, glutathione (GSH), and vitamin C, as well as their corresponding oxidized counterparts. In addition to functioning as enzyme cofactors, these reducing agents have a critical role in dealing with reactive oxygen species (ROS), the toxic products of oxidative metabolism seen as culprits in aging, neurodegenerative disease, and ischemia/ reperfusion injury. Despite this strong relationship between redox and human disease, methods to interrogate a redox pair in vivo are limited. Here we report the development of [1-
13
C] dehydroascorbate [DHA], the oxidized form of Vitamin C, as an endogenous redox sensor for in vivo imaging using hyperpolarized
13
C spectroscopy. In murine models, hyperpolarized [1-
13
C] DHA was rapidly converted to [1-
13
C] vitamin C within the liver, kidneys, and brain, as well as within tumor in a transgenic prostate cancer mouse. This result is consistent with what has been previously described for the DHA/Vitamin C redox pair, and points to a role for hyperpolarized [1-
13
C] DHA in characterizing the concentrations of key intracellular reducing agents, including GSH. More broadly, these findings suggest a prognostic role for this new redox sensor in determining vulnerability of both normal and abnormal tissues to ROS.
Archaic human ancestry in East Asia
Authors: Skoglund Pontus , Jakobsson Mattias
Published: November 2011

Recent studies of ancient genomes have suggested that gene flow from archaic hominin groups to the ancestors of modern humans occurred on two separate occasions during the modern human expansion out of Africa. At the same time, decreasing levels of human genetic diversity have been found at increasing distance from Africa as a consequence of human expansion out of Africa. We analyzed the signal of archaic ancestry in modern human populations, and we investigated how serial founder models of human expansion affect the signal of archaic ancestry using simulations. For descendants of an archaic admixture event, we show that genetic drift coupled with ascertainment bias for common alleles can cause artificial but largely predictable differences in similarity to archaic genomes. In genotype data from non-Africans, this effect results in a biased genetic similarity to Neandertals with increasing distance from Africa. However, in addition to the previously reported gene flow between Neandertals and non-Africans as well as gene flow between an archaic human population from Siberia (“Denisovans”) and Oceanians, we found a significant affinity between East Asians, particularly Southeast Asians, and the Denisova genome—a pattern that is not expected under a model of solely Neandertal admixture in the ancestry of East Asians. These results suggest admixture between Denisovans or a Denisova-related population and the ancestors of East Asians, and that the history of anatomically modern and archaic humans might be more complex than previously proposed.
Estrogen-related receptor-α is a metabolic regulator of effector T-cell activation and differentiation
Authors: Michalek Ryan D. , Gerriets Valerie A. , Nichols Amanda G. , Inoue Makoto , Kazmin Dmitri , Chang Ching-Yi , Dwyer Mary A. , Nelson Erik R. , Pollizzi Kristen N. , Ilkayeva Olga , Giguere Vincent , Zuercher William J. , Powell Jonathan D. , Shinohara Mari L. , McDonnell Donald P. , Rathmell Jeffrey C.
Published: November 2011

Stimulation of resting CD4
+
T lymphocytes leads to rapid proliferation and differentiation into effector (Teff) or inducible regulatory (Treg) subsets with specific functions to promote or suppress immunity. Importantly, Teff and Treg use distinct metabolic programs to support subset specification, survival, and function. Here, we describe that the orphan nuclear receptor estrogen-related receptor-α (ERRα) regulates metabolic pathways critical for Teff. Resting CD4
+
T cells expressed low levels of ERRα protein that increased on activation. ERRα deficiency reduced activated T-cell numbers in vivo and cytokine production in vitro but did not seem to modulate immunity through inhibition of activating signals or viability. Rather, ERRα broadly affected metabolic gene expression and glucose metabolism essential for Teff. In particular, up-regulation of Glut1 protein, glucose uptake, and mitochondrial processes were suppressed in activated ERRα
−/−
T cells and T cells treated with two chemically independent ERRα inhibitors or by shRNAi. Acute ERRα inhibition also blocked T-cell growth and proliferation. This defect appeared as a result of inadequate glucose metabolism, because provision of lipids, but not increased glucose uptake or pyruvate, rescued ATP levels and cell division. Additionally, we have shown that Treg requires lipid oxidation, whereas Teff uses glucose metabolism, and lipid addition selectively restored Treg—but not Teff—generation after acute ERRα inhibition. Furthermore, in vivo inhibition of ERRα reduced T-cell proliferation and Teff generation in both immunization and experimental autoimmune encephalomyelitis models. Thus, ERRα is a selective transcriptional regulator of Teff metabolism that may provide a metabolic means to modulate immunity.
Crucial role for TNF receptor-associated factor 2 (TRAF2) in regulating NFκB2 signaling that contributes to autoimmunity
Authors: Lin Wen-Jye , Su Yu-Wen , Lu Yong-Chen , Hao Zhenyue , Chio Iok In Christine , Chen Nien-Jung , Brüstle Anne , Li Wanda Y. , Mak Tak Wah
Published: November 2011

TNF receptor-associated factor 2 (TRAF2) is a key intracellular signaling mediator that acts downstream of not only TNFα but also various members of the TNFα superfamily. Here, we report that, despite their lack of TNFα signaling, TRAF2
−/−
TNFα
−/−
mice develop an inflammatory disorder characterized by autoantibody accumulation and organ infiltration by T cells with the phenotypes of activated, effector, and memory cells. RAG1
−/−
mice reconstituted with TRAF2
−/−
TNFα
−/−
bone marrow cells showed increased numbers of hyperactive T cells and rapidly developed progressive and eventually lethal inflammation. No inflammation was observed in RAG1
−/−
mice reconstituted with TRAF2
−/−
TNFα
−/−
T-cell receptor β
−/−
or TRAF2
−/−
TNFα
−/−
NFκB-induced kinase
+/−
bone marrow cells. The pathogenic TRAF2
−/−
TNFα
−/−
T cells showed constitutive NFκB2p52 activation and produced elevated levels of T-helper 1 and T-helper 17 cytokines. Our results suggest that a regulatory circuit consisting of TRAF2–NFκB-induced kinase–NFκB2p52 is essential for the proper control of effector T-cell polarization and that loss of T-cell TRAF2 function induces constitutive NFκB2p52 activity that drives fatal autoimmune inflammation independently of TNFα signaling. The involvement of this regulatory circuit in controlling autoimmune responses highlights the delicate balance required to avoid paradoxical adverse events when implementing new targeted anti-inflammatory therapies.
Mst1 and Mst2 protein kinases restrain intestinal stem cell proliferation and colonic tumorigenesis by inhibition of Yes-associated protein (Yap) overabundance
Authors: Zhou Dawang , Zhang Yongyou , Wu Hongtan , Barry Evan , Yin Yi , Lawrence Earl , Dawson Dawn , Willis Joseph E. , Markowitz Sanford D. , Camargo Fernando D. , Avruch Joseph
Published: November 2011

Ablation of the kinases Mst1 and Mst2, orthologs of the
Drosophila
antiproliferative kinase Hippo, from mouse intestinal epithelium caused marked expansion of an undifferentiated stem cell compartment and loss of secretory cells throughout the small and large intestine. Although median survival of mice lacking intestinal Mst1/Mst2 is 13 wk, adenomas of the distal colon are common by this age. Diminished phosphorylation, enhanced abundance, and nuclear localization of the transcriptional coactivator Yes-associated protein 1 (Yap1) is evident in Mst1/Mst2-deficient intestinal epithelium, as is strong activation of β-catenin and Notch signaling. Although biallelic deletion of Yap1 from intestinal epithelium has little effect on intestinal development, inactivation of a single Yap1 allele reduces Yap1 polypeptide abundance to nearly wild-type levels and, despite the continued Yap hypophosphorylation and preferential nuclear localization, normalizes epithelial structure. Thus, supraphysiologic Yap polypeptide levels are necessary to drive intestinal stem cell proliferation. Yap is overexpressed in 68 of 71 human colon cancers and in at least 30 of 36 colon cancer-derived cell lines. In colon-derived cell lines where Yap is overabundant, its depletion strongly reduces β-catenin and Notch signaling and inhibits proliferation and survival. These findings demonstrate that Mst1 and Mst2 actively suppress Yap1 abundance and action in normal intestinal epithelium, an antiproliferative function that frequently is overcome in colon cancer through Yap1 polypeptide overabundance. The dispensability of Yap1 in normal intestinal homeostasis and its potent proliferative and prosurvival actions when overexpressed in colon cancer make it an attractive therapeutic target.
Duplication and partitioning in evolution and function of homoeologous
Q
loci governing domestication characters in polyploid wheat
Authors: Zhang Zengcui , Belcram Harry , Gornicki Piotr , Charles Mathieu , Just Jérémy , Huneau Cécile , Magdelenat Ghislaine , Couloux Arnaud , Samain Sylvie , Gill Bikram S. , Rasmussen Jack B. , Barbe Valérie , Faris Justin D. , Chalhoub Boulos
Published: November 2011

The
Q
gene encodes an
AP2
-like transcription factor that played an important role in domestication of polyploid wheat. The chromosome 5A
Q
alleles (
5AQ
and
5Aq
) have been well studied, but much less is known about the
q
alleles on wheat homoeologous chromosomes 5B (
5Bq
) and 5D (
5Dq
). We investigated the organization, evolution, and function of the
Q/q
homoeoalleles in hexaploid wheat (
Triticum aestivum
L.).
Q/q
gene sequences are highly conserved within and among the A, B, and D genomes of hexaploid wheat, the A and B genomes of tetraploid wheat, and the A, S, and D genomes of the diploid progenitors, but the intergenic regions of the
Q/q
locus are highly divergent among homoeologous genomes. Duplication of the
q
gene 5.8 Mya was likely followed by selective loss of one of the copies from the A genome progenitor and the other copy from the B, D, and S genomes. A recent V
329
-to-I mutation in the A lineage is correlated with the
Q
phenotype. The
5Bq
homoeoalleles became a pseudogene after allotetraploidization. Expression analysis indicated that the homoeoalleles are coregulated in a complex manner. Combined phenotypic and expression analysis indicated that, whereas
5AQ
plays a major role in conferring domestication-related traits,
5Dq
contributes directly and
5Bq
indirectly to suppression of the speltoid phenotype. The evolution of the
Q/q
loci in polyploid wheat resulted in the hyperfunctionalization of
5AQ
, pseudogenization of
5Bq
, and subfunctionalization of
5Dq
, all contributing to the domestication traits.
Ancient DNA suggests the leading role played by men in the Neolithic dissemination
Authors: Lacan Marie , Keyser Christine , Ricaut François-Xavier , Brucato Nicolas , Tarrús Josep , Bosch Angel , Guilaine Jean , Crubézy Eric , Ludes Bertrand
Published: November 2011

The impact of the Neolithic dispersal on the western European populations is subject to continuing debate. To trace and date genetic lineages potentially brought during this transition and so understand the origin of the gene pool of current populations, we studied DNA extracted from human remains excavated in a Spanish funeral cave dating from the beginning of the fifth millennium B.C. Thanks to a “multimarkers” approach based on the analysis of mitochondrial and nuclear DNA (autosomes and Y-chromosome), we obtained information on the early Neolithic funeral practices and on the biogeographical origin of the inhumed individuals. No close kinship was detected. Maternal haplogroups found are consistent with pre-Neolithic settlement, whereas the Y-chromosomal analyses permitted confirmation of the existence in Spain approximately 7,000 y ago of two haplogroups previously associated with the Neolithic transition: G2a and E1b1b1a1b. These results are highly consistent with those previously found in Neolithic individuals from French Late Neolithic individuals, indicating a surprising temporal genetic homogeneity in these groups. The high frequency of G2a in Neolithic samples in western Europe could suggest, furthermore, that the role of men during Neolithic dispersal could be greater than currently estimated.