Embryonic Precursor Cells from the Rhombic Lip Are Specified to a Cerebellar Granule Neuron Identity

AbstractThe specification of diverse classes of neurons is critical to the development of the cerebellar cortex. Here, we describe the purification of early embryonic precursors of cerebellar granule neurons from the rhombic lip, the dorsal aspect of the midbrain/hindbrain region. Isolation of rhombic lip cells reveals a homogenous population of precursor cells that express general neuronal markers and the granule cell marker RU49, but fail to extend neurites or express differentiation markers. Differentiation is induced by coculture with external germinal layer (EGL) cells, or their membranes, suggesting that a local inducing factor acts after formation of the EGL. Thus, proliferating precursors within the rhombic lip are specified to be granule cells very early, with the availability of an inducing factor increasing over the course of development

Stringent Phenomenological Investigation into Heterotic String Optical Unification

For the weakly coupled heterotic string (WCHS) there is a well-known factor of twenty conflict between the minimum string coupling unification scale, Lambda_H ~5x10^(17) GeV, and the projected MSSM unification scale, Lambda_U ~ 2.5x10^(16) GeV, assuming an intermediate scale desert (ISD). Renormalization effects of intermediate scale MSSM-charged exotics (ISME) (endemic to quasi-realistic string models) can resolve this issue, pushing the MSSM scale up to the string scale. However, for a generic string model, this implies that the projected Lambda_U unification under ISD is accidental. If the true unification scale is 5.0x10^(17) GeV, is it possible that illusionary unification at 2.5x10^(17) GeV in the ISD scenario is not accidental? If it is not, then under what conditions would the assumption of ISME in a WCHS model imply apparent unification at Lambda_U when ISD is falsely assumed? Geidt's "optical unification" suggests that Lambda_U is not accidental, by offering a mechanism whereby a generic MSSM scale Lambda_U < Lambda_H is guaranteed. A WCHS model was constructed that offers the possibility of optical unification, depending on the availability of anomaly-cancelling flat directions meeting certain requirements. This paper reports on the systematic investigation of the optical unification properties of the set of stringent flat directions of this model. Stringent flat directions can be guaranteed to be F-flat to all finite order (or to at least a given finite order consistent with electroweak scale supersymmetry breaking) and can be viewed as the likely roots of more general flat directions. Analysis of the phenomenology of stringent flat directions gives an indication of the remaining optical unification phenomenology that must be garnered by flat directions developed from them.Comment: standard latex, 18 pages of tex

What are the experiences of adults returning to work following recovery from Guillain-Barré syndrome? An interpretative phenomenological analysis

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2009 Informa UK Ltd.Purpose. Guillain-Barré syndrome (GBS) is a transient inflammatory disorder affecting peripheral nerves, characterised by weakness and numbness in limbs, upper body and face. Residual problems affect a large minority, and complicate return to work. This qualitative study explored the experiences of people who returned to work following their diagnosis of GBS and recovery, to gain insight into factors that facilitated or inhibited this process. Method. Five people participated in in-depth interviews. Individual and common experiences were explored through interpretative phenomenological analysis. Findings. Three recurring themes are presented: the perceived value of work; losing and recovering a familiar identity at work; and dilemmas around using support and adaptations at work. Certain individual issues also emerged but are beyond the scope of this article. Participants tended to measure their recovery in terms of returning to work yet continued to experience certain physical and psychosocial difficulties at work related to GBS, which required active coping strategies. Limited public awareness of GBS was perceived as a hindrance when returning to work. Conclusion. This study provides a rich account of the experiences that people encounter returning to work following GBS. Rehabilitation specialists may offer more effective preparation for this process, drawing upon the issues identified

Motivations for contralateral prophylactic mastectomy as a function of socioeconomic status

BACKGROUND: Despite no demonstrated survival advantage for women at average risk of breast cancer, rates of contralateral prophylactic mastectomy (CPM) continue to increase. Research reveals women with higher socioeconomic status (SES) are more likely to select CPM. This study examines how indicators of SES, age, and disease severity affect CPM motivations. METHODS: Patients (N = 113) who underwent CPM at four Indiana University affiliated hospitals completed telephone interviews in 2013. Participants answered questions about 11 CPM motivations and provided demographic information. Responses to motivation items were factor analyzed, resulting in 4 motivational factors: reducing long-term risk, symmetry, avoiding future medical visits, and avoiding treatments. RESULTS: Across demographic differences, reducing long-term risk was the strongest CPM motivation. Lower income predicted stronger motivation to reduce long-term risk and avoid treatment. Older participants were more motivated to avoid treatment; younger and more-educated patients were more concerned about symmetry. Greater severity of diagnosis predicted avoiding treatments. CONCLUSIONS: Reducing long-term risk is the primary motivation across groups, but there are also notable differences as a function of age, education, income, and disease severity. To stop the trend of increasing CPM, physicians must tailor patient counseling to address motivations that are consistent across patient populations and those that vary between populations

Social Network, Surgeon, and Media Influence on the Decision to Undergo Contralateral Prophylactic Mastectomy

OBJECTIVES: The rate of contralateral prophylactic mastectomy (CPM) has risen sharply in the past decade. The current study was designed to examine social network, surgeon, and media influence on patients' CPM decision-making, examining not only who influenced the decision, and to what extent, but also the type of influence exerted. METHODS: Patients (N=113) who underwent CPM at 4 Indiana University-affiliated hospitals between 2008 and 2012 completed structured telephone interviews in 2013. Questions addressed the involvement and influence of the social network (family, friends, and nonsurgeon health professionals), surgeon, and media on the CPM decision. RESULTS: Spouses, children, family, friends, and health professionals were reported as exerting a meaningful degree of influence on patients' decisions, largely in ways that were positive or neutral toward CPM. Most surgeons were regarded as providing options rather than encouraging or discouraging CPM. Media influence was present, but limited. CONCLUSIONS: Patients who choose CPM do so with influence and support from members of their social networks. Reversing the increasing choice of CPM will require educating these influential others, which can be accomplished by encouraging patients to include them in clinical consultations, and by providing patients with educational materials that can be shared with their social networks. Surgeons need to be perceived as having an opinion, specifically that CPM should be reserved for those patients for whom it is medically indicated

A dynamic network approach for the study of human phenotypes

The use of networks to integrate different genetic, proteomic, and metabolic datasets has been proposed as a viable path toward elucidating the origins of specific diseases. Here we introduce a new phenotypic database summarizing correlations obtained from the disease history of more than 30 million patients in a Phenotypic Disease Network (PDN). We present evidence that the structure of the PDN is relevant to the understanding of illness progression by showing that (1) patients develop diseases close in the network to those they already have; (2) the progression of disease along the links of the network is different for patients of different genders and ethnicities; (3) patients diagnosed with diseases which are more highly connected in the PDN tend to die sooner than those affected by less connected diseases; and (4) diseases that tend to be preceded by others in the PDN tend to be more connected than diseases that precede other illnesses, and are associated with higher degrees of mortality. Our findings show that disease progression can be represented and studied using network methods, offering the potential to enhance our understanding of the origin and evolution of human diseases. The dataset introduced here, released concurrently with this publication, represents the largest relational phenotypic resource publicly available to the research community.Comment: 28 pages (double space), 6 figure

of Education or Offices within it. NCEO Core Staff

assessment: Results of a comparative study (Technical Report 64). Minneapolis, MN: University of Minnesota, National Center on Educationa

Fire as a fundamental ecological process: Research advances and frontiers

© 2020 The Authors. Journal of Ecology published by John Wiley & Sons Ltd on behalf of British Ecological Society Fire is a powerful ecological and evolutionary force that regulates organismal traits, population sizes, species interactions, community composition, carbon and nutrient cycling and ecosystem function. It also presents a rapidly growing societal challenge, due to both increasingly destructive wildfires and fire exclusion in fire-dependent ecosystems. As an ecological process, fire integrates complex feedbacks among biological, social and geophysical processes, requiring coordination across several fields and scales of study. Here, we describe the diversity of ways in which fire operates as a fundamental ecological and evolutionary process on Earth. We explore research priorities in six categories of fire ecology: (a) characteristics of fire regimes, (b) changing fire regimes, (c) fire effects on above-ground ecology, (d) fire effects on below-ground ecology, (e) fire behaviour and (f) fire ecology modelling. We identify three emergent themes: the need to study fire across temporal scales, to assess the mechanisms underlying a variety of ecological feedbacks involving fire and to improve representation of fire in a range of modelling contexts. Synthesis: As fire regimes and our relationships with fire continue to change, prioritizing these research areas will facilitate understanding of the ecological causes and consequences of future fires and rethinking fire management alternatives

The Role of Thioredoxin Reductases in Brain Development

The thioredoxin-dependent system is an essential regulator of cellular redox balance. Since oxidative stress has been linked with neurodegenerative disease, we studied the roles of thioredoxin reductases in brain using mice with nervous system (NS)-specific deletion of cytosolic (Txnrd1) and mitochondrial (Txnrd2) thioredoxin reductase. While NS-specific Txnrd2 null mice develop normally, mice lacking Txnrd1 in the NS were significantly smaller and displayed ataxia and tremor. A striking patterned cerebellar hypoplasia was observed. Proliferation of the external granular layer (EGL) was strongly reduced and fissure formation and laminar organisation of the cerebellar cortex was impaired in the rostral portion of the cerebellum. Purkinje cells were ectopically located and their dendrites stunted. The Bergmann glial network was disorganized and showed a pronounced reduction in fiber strength. Cerebellar hypoplasia did not result from increased apoptosis, but from decreased proliferation of granule cell precursors within the EGL. Of note, neuron-specific inactivation of Txnrd1 did not result in cerebellar hypoplasia, suggesting a vital role for Txnrd1 in Bergmann glia or neuronal precursor cells