208 research outputs found
Internally coupled ears in living mammals.
It is generally held that the right and left middle ears of mammals are acoustically isolated from each other, such that mammals must rely on neural computation to derive sound localisation cues. There are, however, some unusual species in which the middle ear cavities intercommunicate, in which case each ear might be able to act as a pressure-difference receiver. This could improve sound localisation at lower frequencies. The platypus Ornithorhynchus is apparently unique among mammals in that its tympanic cavities are widely open to the pharynx, a morphology resembling that of some non-mammalian tetrapods. The right and left middle ear cavities of certain talpid and golden moles are connected through air passages within the basicranium; one experimental study on Talpa has shown that the middle ears are indeed acoustically coupled by these means. Having a basisphenoid component to the middle ear cavity walls could be an important prerequisite for the development of this form of interaural communication. Little is known about the hearing abilities of platypus, talpid and golden moles, but their audition may well be limited to relatively low frequencies. If so, these mammals could, in principle, benefit from the sound localisation cues available to them through internally coupled ears. Whether or not they actually do remains to be established experimentally.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00422-015-0675-
Super-resolution imaging as a method to study GPCR dimers and higher-order oligomers
The study of G protein-coupled receptor (GPCR) dimers and higher-order oligomers has unveiled mechanisms for receptors to diversify signaling and potentially uncover novel therapeutic targets. The functional and clinical significance of these receptor–receptor associations has been facilitated by the development of techniques and protocols, enabling researchers to unpick their function from the molecular interfaces, to demonstrating functional significance in vivo, in both health and disease. Here we describe our methodology to study GPCR oligomerization at the single-molecule level via super-resolution imaging. Specifically, we have employed photoactivated localization microscopy, with photoactivatable dyes (PD-PALM) to visualize the spatial organization of these complexes to <10 nm resolution, and the quantitation of GPCR monomer, dimer, and oligomer in both homomeric and heteromeric forms. We provide guidelines on optimal sample preparation, imaging parameters, and necessary controls for resolving and quantifying single-molecule data. Finally, we discuss advantages and limitations of this imaging technique and its potential future applications to the study of GPCR function
Hes1 Is Required for Appropriate Morphogenesis and Differentiation during Mouse Thyroid Gland Development
Notch signalling plays an important role in endocrine development, through its target gene Hes1. Hes1, a bHLH transcriptional repressor, influences progenitor cell proliferation and differentiation. Recently, Hes1 was shown to be expressed in the thyroid and regulate expression of the sodium iodide symporter (Nis). To investigate the role of Hes1 for thyroid development, we studied thyroid morphology and function in mice lacking Hes1. During normal mouse thyroid development, Hes1 was detected from E9.5 onwards in the median anlage, and at E11.5 in the ultimobranchial bodies. Hes1−/− mouse embryos had a significantly lower number of Nkx2-1-positive progenitor cells (p<0.05) at E9.5 and at E11.5. Moreover, Hes1−/− mouse embryos showed a significantly smaller total thyroid surface area (−40 to −60%) compared to wild type mice at all study time points (E9.5−E16.5). In both Hes1−/− and wild type mouse embryos, most Nkx2-1-positive thyroid cells expressed the cell cycle inhibitor p57 at E9.5 in correlation with low proliferation index. In Hes1−/− mouse embryos, fusion of the median anlage with the ultimobranchial bodies was delayed by 3 days (E16.5 vs. E13.5 in wild type mice). After fusion of thyroid anlages, hypoplastic Hes1−/− thyroids revealed a significantly decreased labelling area for T4 (−78%) and calcitonin (−65%) normalized to Nkx2-1 positive cells. Decreased T4-synthesis might be due to reduced Nis labelling area (−69%). These findings suggest a dual role of Hes1 during thyroid development: first, control of the number of both thyrocyte and C-cell progenitors, via a p57-independent mechanism; second, adequate differentiation and endocrine function of thyrocytes and C-cells
Differences in physical activity domains, guideline adherence, and weight history between metabolically healthy and metabolically abnormal obese adults: a cross-sectional study
BACKGROUND: Despite the accepted health consequences of obesity, emerging research suggests that a significant segment of adults with obesity are metabolically healthy (MHO). To date, MHO individuals have been shown to have higher levels of physical activity (PA), but little is known about the importance of PA domains or the influence of weight history compared to their metabolically abnormal (MAO) counterpart. OBJECTIVE: To evaluate the relationship between PA domains, PA guideline adherence, and weight history on MHO. METHODS: Pooled cycles of the National Health and Nutritional Examination Survey (NHANES) 1999–2006 (≥20 y; BMI ≥ 30 kg/m(2); N = 2,753) and harmonized criteria for metabolic syndrome (MetS) were used. Participants were categorized as “inactive” (no reported PA), “somewhat active” (>0 to < 500 metabolic equivalent (MET) min/week), and “active” (PA guideline adherence, ≥ 500 MET min/week) according to each domain of PA (total, recreational, transportation and household). Logistic and multinomial regressions were modelled for MHO and analyses were adjusted for age, sex, education, ethnicity, income, smoking and alcohol intake. RESULTS: Compared to MAO, MHO participants were younger, had lower BMI, and were more likely to be classified as active according to their total and recreational PA level. Based on total PA levels, individuals who were active had a 70 % greater likelihood of having the MHO phenotype (OR = 1.70, 95 % CI: 1.19–2.43); however, once stratified by age (20–44 y; 45–59 y; and; ≥60 y), the association remained significant only amongst those aged 45–59 y. Although moderate and vigorous PA were inconsistently related to MHO following adjustment for covariates, losing ≥30 kg in the last 10 y and not gaining ≥10 kg since age 25 y were significant predictors of MHO phenotype for all PA domains, even if adherence to the PA guidelines were not met. CONCLUSION: Although PA is associated with MHO, the beneficial effects of PA may be moderated by longer-term changes in weight. Longitudinal analysis of physical activity and weight change trajectories are necessary to isolate the contribution of duration of obesity, PA behaviours, and longer-term outcomes amongst MHO individuals
Discrete breathers in and related models
We touch upon the wide topic of discrete breather formation with a special
emphasis on the the model. We start by introducing the model and
discussing some of the application areas/motivational aspects of exploring time
periodic, spatially localized structures, such as the discrete breathers. Our
main emphasis is on the existence, and especially on the stability features of
such solutions. We explore their spectral stability numerically, as well as in
special limits (such as the vicinity of the so-called anti-continuum limit of
vanishing coupling) analytically. We also provide and explore a simple, yet
powerful stability criterion involving the sign of the derivative of the energy
vs. frequency dependence of such solutions. We then turn our attention to
nonlinear stability, bringing forth the importance of a topological notion,
namely the Krein signature. Furthermore, we briefly touch upon linearly and
nonlinearly unstable dynamics of such states. Some special aspects/extensions
of such structures are only touched upon, including moving breathers and
dissipative variations of the model and some possibilities for future work are
highlighted
Selection of the appropriate method for the assessment of insulin resistance
Insulin resistance is one of the major aggravating factors for metabolic syndrome. There are many methods available for estimation of insulin resistance which range from complex techniques down to simple indices. For all methods of assessing insulin resistance it is essential that their validity and reliability is established before using them as investigations. The reference techniques of hyperinsulinaemic euglycaemic clamp and its alternative the frequently sampled intravenous glucose tolerance test are the most reliable methods available for estimating insulin resistance. However, many simple methods, from which indices can be derived, have been assessed and validated e.g. homeostasis model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI). Given the increasing number of simple indices of IR it may be difficult for clinicians and researchers to select the most appropriate index for their studies. This review therefore provides guidelines and advices which must be considered before proceeding with a study
Quantitative Multicolor Super-Resolution Microscopy Reveals Tetherin HIV-1 Interaction
Virus assembly and interaction with host-cell proteins occur at length scales below the diffraction limit of visible light. Novel super-resolution microscopy techniques achieve nanometer resolution of fluorescently labeled molecules. The cellular restriction factor tetherin (also known as CD317, BST-2 or HM1.24) inhibits the release of human immunodeficiency virus 1 (HIV-1) through direct incorporation into viral membranes and is counteracted by the HIV-1 protein Vpu. For super-resolution analysis of HIV-1 and tetherin interactions, we established fluorescence labeling of HIV-1 proteins and tetherin that preserved HIV-1 particle formation and Vpu-dependent restriction, respectively. Multicolor super-resolution microscopy revealed important structural features of individual HIV-1 virions, virus assembly sites and their interaction with tetherin at the plasma membrane. Tetherin localization to micro-domains was dependent on both tetherin membrane anchors. Tetherin clusters containing on average 4 to 7 tetherin dimers were visualized at HIV-1 assembly sites. Combined biochemical and super-resolution analysis revealed that extended tetherin dimers incorporate both N-termini into assembling virus particles and restrict HIV-1 release. Neither tetherin domains nor HIV-1 assembly sites showed enrichment of the raft marker GM1. Together, our super-resolution microscopy analysis of HIV-1 interactions with tetherin provides new insights into the mechanism of tetherin-mediated HIV-1 restriction and paves the way for future studies of virus-host interactions
The Nature Index: A General Framework for Synthesizing Knowledge on the State of Biodiversity
The magnitude and urgency of the biodiversity crisis is widely recognized within
scientific and political organizations. However, a lack of integrated measures
for biodiversity has greatly constrained the national and international response
to the biodiversity crisis. Thus, integrated biodiversity indexes will greatly
facilitate information transfer from science toward other areas of human
society. The Nature Index framework samples scientific information on
biodiversity from a variety of sources, synthesizes this information, and then
transmits it in a simplified form to environmental managers, policymakers, and
the public. The Nature Index optimizes information use by incorporating expert
judgment, monitoring-based estimates, and model-based estimates. The index
relies on a network of scientific experts, each of whom is responsible for one
or more biodiversity indicators. The resulting set of indicators is supposed to
represent the best available knowledge on the state of biodiversity and
ecosystems in any given area. The value of each indicator is scaled relative to
a reference state, i.e., a predicted value assessed by each expert for a
hypothetical undisturbed or sustainably managed ecosystem. Scaled indicator
values can be aggregated or disaggregated over different axes representing
spatiotemporal dimensions or thematic groups. A range of scaling models can be
applied to allow for different ways of interpreting the reference states, e.g.,
optimal situations or minimum sustainable levels. Statistical testing for
differences in space or time can be implemented using Monte-Carlo simulations.
This study presents the Nature Index framework and details its implementation in
Norway. The results suggest that the framework is a functional, efficient, and
pragmatic approach for gathering and synthesizing scientific knowledge on the
state of biodiversity in any marine or terrestrial ecosystem and has general
applicability worldwide
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