The Role of the Mucus Barrier in Digestion

Mucus forms a protective layer across a variety of epithelial surfaces. In the gastrointestinal (GI) tract, the barrier has to permit the uptake of nutrients, while excluding potential hazards, such as pathogenic bacteria. In this short review article, we look at recent literature on the structure, location, and properties of the mammalian intestinal secreted mucins and the mucus layer they form over a wide range of length scales. In particular, we look at the structure of the gel-forming glycoprotein MUC2, the primary intestinal secreted mucin, and the influence this has on the properties of the mucus layer. We show that, even at the level of the protein backbone, MUC2 is highly heterogeneous and that this is reflected in the networks it forms. It is evident that a combination of charge and pore size determines what can diffuse through the layer to the underlying gut epithelium. This information is important for the targeted delivery of bioactive molecules, including nutrients and pharmaceuticals, and for understanding how GI health is maintained

Altered innate defenses in the neonatal gastrointestinal tract in response to colonization by neuropathogenic Escherichia coli

Two-day-old (P2), but not nine-day-old (P9), rat pups are susceptible to systemic infection following gastrointestinal colonization by Escherichia coli K1. Age dependency reflects the capacity of colonizing K1 to translocate from gastrointestinal (GI) tract to blood. A complex GI microbiota developed by P2, showed little variation over P2-P9 and did not prevent stable K1 colonization. Substantial developmental expression was observed over P2-P9, including up-regulation of genes encoding components of the small intestinal (α-defensins Defa24 and Defa-rs1) and colonic (trefoil factor Tff2) mucus barrier. K1 colonization modulated expression of these peptides: developmental expression of Tff2 was dysregulated in P2 tissues and was accompanied by a decrease in mucin Muc2. Conversely, α-defensin genes were up-regulated in P9 tissues. We propose that incomplete development of the mucus barrier during early neonatal life and the capacity of colonizing K1 to interfere with mucus barrier maturation provide opportunities for neuropathogen translocation into the bloodstream

Predator-Induced Vertical Behavior of a Ctenophore

Although many studies have focused on Mnemiopsis leidyi predation, little is known about the role of this ctenophore as prey when abundant in native and invaded pelagic systems. We examined the response of the ctenophore M. leidyi to the predatory ctenophore Beroe ovata in an experiment in which the two species could potentially sense each other while being physically separated. On average, M. leidyi responded to the predator’s presence by increasing variability in swimming speeds and by lowering their vertical distribution. Such behavior may help explain field records of vertical migration, as well as stratified and near-bottom distributions of M. leidyi

A Case of Hypothyroidism and Type 2 Diabetes Associated with Type V Hyperlipoproteinemia and Eruptive Xanthomas

Primary hypothyroidism and type 2 diabetes are both typically associated with the increased level of triglycerides. To date, there have been only a few case reports of type 2 diabetes patients with both type V hyperlipoproteinemia and eruptive xanthomas, but there have been no reports of hypothyroidism patients associated with eruptive xanthomas. We report here on a case of a 48-yr old female patient who was diagnosed with type 2 diabetes and primary hypothyroidism associated with both type V hyperlipoproteinemia and eruptive xanthomas. We found rouleaux formation of RBCs in peripheral blood smear, elevated TSH, and low free T4 level, and dyslipidemia (total cholesterol 18.1 mM/L, triglyceride 61.64 mM/L, HDL 3.0 mM/L, and LDL 2.54 mM/L). She has taken fenofibrate, levothyroxine, and oral hypoglycemic agent for 4 months. After treatment, both TSH level and lipid concentration returned to normal range, and her yellowish skin nodules have also disappeared

Interactions between Predation and Resources Shape Zooplankton Population Dynamics

Identifying the relative importance of predation and resources in population dynamics has a long tradition in ecology, while interactions between them have been studied less intensively. In order to disentangle the effects of predation by juvenile fish, algal resource availability and their interactive effects on zooplankton population dynamics, we conducted an enclosure experiment where zooplankton were exposed to a gradient of predation of roach (Rutilus rutilus) at different algal concentrations. We show that zooplankton populations collapse under high predation pressure irrespective of resource availability, confirming that juvenile fish are able to severely reduce zooplankton prey when occurring in high densities. At lower predation pressure, however, the effect of predation depended on algal resource availability since high algal resource supply buffered against predation. Hence, we suggest that interactions between mass-hatching of fish, and the strong fluctuations in algal resources in spring have the potential to regulate zooplankton population dynamics. In a broader perspective, increasing spring temperatures due to global warming will most likely affect the timing of these processes and have consequences for the spring and summer zooplankton dynamics

Molecular Structure and Dimeric Organization of the Notch Extracellular Domain as Revealed by Electron Microscopy

Background: The Notch receptor links cell fate decisions of one cell to that of the immediate cellular neighbor. In humans, malfunction of Notch signaling results in diseases and congenital disorders. Structural information is essential for gaining insight into the mechanism of the receptor as well as for potentially interfering with its function for therapeutic purposes. Methodology/Principal Findings: We used the Affinity Grid approach to prepare specimens of the Notch extracellular domain (NECD) of the Drosophila Notch and human Notch1 receptors suitable for analysis by electron microscopy and three-dimensional (3D) image reconstruction. The resulting 3D density maps reveal that the NECD structure is conserved across species. We show that the NECD forms a dimer and adopts different yet defined conformations, and we identify the membrane-proximal region of the receptor and its ligand-binding site. Conclusions/Significance: Our results provide direct and unambiguous evidence that the NECD forms a dimer. Our studies further show that the NECD adopts at least three distinct conformations that are likely related to different functional states of the receptor. These findings open the way to now correlate mutations in the NECD with its oligomeric state and conformation

Newly diagnosed incident dizziness of older patients: a follow-up study in primary care

<p>Abstract</p> <p>Background</p> <p>Dizziness is a common complaint of older patients in primary care, yet not much is known about the course of incident dizziness. The aim of the study was to follow-up symptoms, subjective impairments and needs of older patients (≥65) with incident dizziness and to determine predictors of chronic dizziness. Furthermore, we analysed general practitioners' (GPs') initial diagnoses, referrals and revised diagnoses after six months.</p> <p>Methods</p> <p>An observational study was performed in 21 primary care practices in Germany, including a four-week and six-month follow-up. A questionnaire comprising characteristic matters of dizziness and a series of validated instruments was completed by 66 participants during enrolment and follow-up (after 1 month and 6 months). After six months, chart reviews and face-to-face interviews were also performed with the GPs.</p> <p>Results</p> <p>Mean scores of dizziness handicap, depression and quality of life were not or only slightly affected, and did not deteriorate during follow-up; however, 24 patients (34.8%) showed a moderate or severe dizziness handicap, and 43 (62.3%) showed a certain disability in terms of quality of life at the time of enrolment. In multivariate analysis, n = 44 patients suffering from chronic dizziness (dependent variable, i.e. relapsing or persistent at six months) initially had a greater dizziness handicap (OR 1.42, 95%CI 1.05-1.47) than patients with transient dizziness. GPs referred 47.8% of the patients to specialists who detected two additional cases of benign paroxysmal positional vertigo (BPPV).</p> <p>Conclusions</p> <p>New-onset dizziness relapsed or persisted in a considerable number of patients within six months. This was difficult to predict due to the patients' heterogeneous complaints and characteristics. Symptom persistence does not seem to be associated with deterioration of the psychological status in older primary care patients. Management strategies should routinely consider BPPV as differential diagnosis.</p

Association of MC1R Variants and host phenotypes with melanoma risk in CDKN2A mutation carriers: a GenoMEL study

&lt;p&gt;&lt;b&gt;Background&lt;/b&gt; Carrying the cyclin-dependent kinase inhibitor 2A (CDKN2A) germline mutations is associated with a high risk for melanoma. Penetrance of CDKN2A mutations is modified by pigmentation characteristics, nevus phenotypes, and some variants of the melanocortin-1 receptor gene (MC1R), which is known to have a role in the pigmentation process. However, investigation of the associations of both MC1R variants and host phenotypes with melanoma risk has been limited.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods&lt;/b&gt; We included 815 CDKN2A mutation carriers (473 affected, and 342 unaffected, with melanoma) from 186 families from 15 centers in Europe, North America, and Australia who participated in the Melanoma Genetics Consortium. In this family-based study, we assessed the associations of the four most frequent MC1R variants (V60L, V92M, R151C, and R160W) and the number of variants (1, &#8805;2 variants), alone or jointly with the host phenotypes (hair color, propensity to sunburn, and number of nevi), with melanoma risk in CDKN2A mutation carriers. These associations were estimated and tested using generalized estimating equations. All statistical tests were two-sided.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results&lt;/b&gt; Carrying any one of the four most frequent MC1R variants (V60L, V92M, R151C, R160W) in CDKN2A mutation carriers was associated with a statistically significantly increased risk for melanoma across all continents (1.24 × 10−6 &#8804; P &#8804; .0007). A consistent pattern of increase in melanoma risk was also associated with increase in number of MC1R variants. The risk of melanoma associated with at least two MC1R variants was 2.6-fold higher than the risk associated with only one variant (odds ratio = 5.83 [95% confidence interval = 3.60 to 9.46] vs 2.25 [95% confidence interval = 1.44 to 3.52]; Ptrend = 1.86 × 10−8). The joint analysis of MC1R variants and host phenotypes showed statistically significant associations of melanoma risk, together with MC1R variants (.0001 &#8804; P &#8804; .04), hair color (.006 &#8804; P &#8804; .06), and number of nevi (6.9 × 10−6 &#8804; P &#8804; .02).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusion&lt;/b&gt; Results show that MC1R variants, hair color, and number of nevi were jointly associated with melanoma risk in CDKN2A mutation carriers. This joint association may have important consequences for risk assessments in familial settings.&lt;/p&gt

Translocation as a Novel Approach to Study Effects of a New Breeding Habitat on Reproductive Output in Wild Birds

Environmental conditions under which species reproduce have major consequences on breeding success and subsequent fitness. Therefore breeding habitat choice is ultimately important. Studies rarely address the potential fitness pay-offs of alternative natural breeding habitats by experimental translocation. Here we present a new tool to study fitness consequences of free living birds in different habitats. We translocated a migratory passerine, the pied flycatcher (Ficedula hypoleuca), to a novel site, where pairs were subjected to a short stay (2–4 days) in a nest box-equipped aviary before being released. We show that it is technically possible to retain birds in the new area for breeding, allowing the study of reproductive consequences of dispersal under natural conditions. The translocation resulted in an extension of the interval between arrival and egg laying of four days, highlighting the importance of having an adequate control group. Clutch size and nestling parameters did not differ significantly between translocated and unmanipulated females, which suggests that the procedure did not affect birds in their reproductive performance later on. This method could be applied broadly in evolutionary and ecological research, e.g., to study the potential fitness benefits and costs for dispersing to more northern latitudes as a way of adapting to climate change