The Efficacy of a Diet Low in Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols (FODMAPs) in the Treatment of Irritable Bowel Syndrome

This paper reviews the efficacy of the low-FODMAP (Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols) diet in treating the symptoms associated with irritable bowel syndrome (IBS). Since IBS has a wide range of etiologies and symptoms, it is often difficult to treat. A large majority of patients report their symptoms being associated with their diet. Researchers have shown that specific components of food, FODMAPs, may play a role in exacerbating symptoms. In this literary review, the physiological effects and the efficacy of the low-FODMAP diet was explored using current literature. In conclusion, the low-FODMAP diet may be an efficacious treatment option for those diagnosed with IBS

Analyse Neurone-generierender Zellteilungen im Neuroepithel der Maus

In Vertebraten wird Dauer der Proliferationsphase neuronaler Vorläuferzellen im Neuroepithel (Neuroepithelzellen) und damit die Neuronenzahl des Gehirns vermutlich durch den Übergang von im cell fate symmetrischen, proliferativen (Generierung zweier Neuroepithelzellen) zu asymmetrischen differenzierenden Zellteilungen (Generierung einer Neuroepithelzelle und eines Neurons) kontrolliert. Direkte Beweise für die Existenz dieser asymmetrischen Teilungen stehen noch aus, genauso wie zellbiologische Mechanismen und genetische Kontrolle des „Umschaltens“ unbekannt sind. Durch die Expression von GFP unter Kontrolle regulatorischer Sequenzen des TIS21-Gens wurden spezifisch Neurone-generierende Neuroepithelzellen markiert, um (i) die Symmetrie der Neurone-generierenden Zellteilung videomikroskopisch zu untersuchen und (ii) eine differenzielle Analyse der Zellbiologie (z.B. Verteilung apikaler Membran, Zellzyklusdauer) und Genexpression von proliferierenden vs. Neurone-generierenden Neuroepithelzellen zu ermöglichen. Es wurden drei transgene und eine TIS21-GFP-knock in-Mauslinie etabliert. Im TIS21-GFP-knock in ersetzt eine GFP-Expressionskassette das offene Leseraster von TIS21 in Exon 1. Der TIS21-GFP-knock in exprimiert entlang des ganzen Neuralrohrs GFP in Neurone-generierenden Neuroepithelzellen, die transgenen Linien jeweils nur in bestimmten Abschnitten. Die Expression von TIS21 im Neuroepithel wird offensichtlich von verschiedenen Elementen gesteuert, die jeweils bestimmte Regionen im Neuralrohr abdecken. In Schnittkulturen von Neuralrohr-Explantaten aus TIS21-GFP-knock in-Embryonen wurden mit Multiphoton-Videomikroskopie zu Beginn der Neurogenese (E12 Telencephalon) neben sich apikal teilenden Zellen auch überraschend Zellen entdeckt, die sich auf der basalen Seite des Neuroepithels teilen. Apikalen Teilungen bilden wahrscheinlich ein Neuron und eine Neuroepithelzelle, basale bilden zwei Neurone. Demnach existieren in Vertebraten zwei Typen Neurone-generierender Teilungen: (i) im cell fate asymmetrische, apikale Teilungen typischer Neuroepithelzellen und (ii) symmetrische, basale Teilungen einer hier erstmals beschriebenen Zellpopulation. Die Verteilung apikaler Membran und die Zellzykluslänge wurden in proliferierenden vs. Neurone-generierenden Neuroepithelzellen als mögliche Steuerungsmechanismen des Übergangs von Proliferation zu Neurogenese untersucht. Die Orientierung der Teilungsebene (abgeleitet aus der Chromatinfärbung in der Anaphase) relativ zur apikalen Membran identifiziert als Lücke in der basolateralen, Cadherin-positiven Plasmamembran in frühen Stadien der Neurogenese (E10..5-E11.5) im TIS21-GFP-knock in zeigt, dass der Schritt von Proliferation zu Neurogenese durch einen Wechsel in der Verteilung apikaler Membrankomponenten kontrolliert werden könnte: Apikale Teilungen mit symmetrischer Verteilung der apikalen Membran sind größtenteils proliferierend, Teilungen mit asymmetrischer Verteilung der apikalen Membran Neurone-generierend. Zudem korreliert die Differenzierung mit einer Verlängerung des Zellzyklus: Durch eine kumulative BrdU-Markierung konnte gezeigt werden, dass sich zu Beginn der Neurogenese (E10.5 Telencephalon) der Zellzyklus der Neurone-generierenden Neuroepithelzellen um 40% auf 13 h, gegenüber 9 h in proliferierenden Neuroepithelzellen, verlangsamt. Eine ursächliche Beteiligung von TIS21, das spezifisch in Neurone-generierenden also sich langsamen teilenden Neuroepithelzellen exprimiert ist und bekanntermaßen Zellzyklus-verlangsamend wirkt, an diesem Phänomen ist noch nicht geklärt. Homozygote TIS21-GFP-knock in-Tiere, als TIS21-knock out-Modell, zeigen zumindest keinen offensichtlichen qualitativ veränderten Ablauf der Neurogenese. Dagegen verschiebt sich im Blutbild das Gleichgewicht von Lymphozyten zu Granulocyten. In Verbindung mit dem in dieser Arbeit beschriebenen embryonalen und adulten Aktivitätsmuster - TIS21 ist in differenzierenden Zellpopulationen verschiedener Gewebe exprimiert - impliziert dies eine allgemeine physiologische Funktion von TIS21 bei Proliferations- und Differenzierungsprozessen. In einer unabhängigen Serie von Experimenten wurde die Möglichkeit untersucht, durch RNA-interference (RNAi) spezifisch die Expression von Genen in postimplantorischen Mausembryonen zu unterdrücken. Konkret wurde esi-(endoribonuclease III-prepared short interfering)-RNA (esiRNA) in E10 Mäuseembryonen intraventrikulär injiziert, durch Elektroporation in Neuroepithelzellen transfiziert und der Effekt von RNAi nach 24 h in vitro-Kultur der Embryonen analysiert. esiRNA gegen b-Galaktosidase, koelektroporiert mit einem b-Galaktosidase- und einem GFP-Expressionsvektor, inhibierte spezifisch die b-Galaktosidase- nicht aber die GFP-Expression. In einem analogen Experiment in E10 TIS21-GFP-knock in Embryonen verhinderte die Elektroporation von esiRNA gerichtet gegen GFP die GFP-Expression zu Beginn der Neurogenese – d.h. die Expression eines endogen exprimierten Gens

Central amygdala PKC-δ^+ neurons mediate the influence of multiple anorexigenic signals

Feeding can be inhibited by multiple cues, including those associated with satiety, sickness or unpalatable food. How such anorexigenic signals inhibit feeding at the neural circuit level is not completely understood. Although some inhibitory circuits have been identified, it is not yet clear whether distinct anorexigenic influences are processed in a convergent or parallel manner. The amygdala central nucleus (CEA) has been implicated in feeding control, but its role is controversial. The lateral subdivision of CEA (CEl) contains a subpopulation of GABAergic neurons that are marked by protein kinase C-δ (PKC-δ). We found that CEl PKC-δ^+ neurons in mice were activated by diverse anorexigenic signals in vivo, were required for the inhibition of feeding by such signals and strongly suppressed food intake when activated. They received presynaptic inputs from anatomically distributed neurons activated by different anorexigenic agents. Our data suggest that CEl PKC-δ^+ neurons constitute an important node that mediates the influence of multiple anorexigenic signals

Regulation and Measurement of Nitrification in Terrestrial Systems

Nitric oxide (NO) is a relatively short-lived trace gas that reacts with oxygen in the troposphere to produce the air pollutant ozone. It also reacts with water vapor to form nitric and nitrous acids, which acidify precipitation and increase N deposition. Models currently used to predict soil NO fluxes are based on the assumption that NO flux is proportional to the gross rate of nitrification or N mineralization; however, this assumption has not been tested because of the difficulty in measuring gross N-cycling rates in situ. We measured soil NO fluxes, gross and net N-cycling rates, and a variety of other soil characteristics in the forest floor and intact soil cores at nine undisturbed forest and rangeland ecosystems of New Mexico, Utah, and Oregon, USA, to determine which soil variables were most closely related to soil NO flux. Soil NO fluxes ranged from a low of 0.02 ng N·m22·s21, prior to wetting in a western hemlock–sitka spruce forest on the Oregon coast, to a high of 6.74 ng N·m22·s21, one hour after soil wetting in a juniper woodland of central Oregon. In contrast to our expectations, neither gross nitrification nor gross mineralization was correlated with soil NO flux. Fluxes were positively correlated with net rates of mineralization and nitrification, soil NO3 2 concentrations, bulk density, and pH, and negatively correlated with gross rates of NO3 2 consumption in the forest floor, soil organic carbon (SOC), soil C:N, and soil water content. Principal-component analysis showed that NO flux after water addition (2 cm of water) had a strong negative correlation with microbial demand for N (as indicated by net mineralization, net nitrification, SOC, and C:N). Our results suggest that, even in well-drained soils, NO efflux is limited more by NO consumption than by NO production. As a result, models utilizing the more easily measured net rates, rather than gross rates, may be better predictors of soil NO fluxes across a range of ecosystems

Relativity, rank and the utility of income

This is the accepted version of the following article: Rablen, M. D. (2008), Relativity, Rank and the Utility of Income. The Economic Journal, 118: 801–821, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/j.1468-0297.2008.02143.x/abstract.Relative utility has become an important concept in several disjoint areas of economics. I present a cardinal model of income utility based on the supposition that agents care about their rank in the income distribution and that utility is subject to adaptation over time. Utility levels correspond to the Leyden Individual Welfare Function while utility differences yield a version of the prospect theory value function, thereby providing a new and shared derivation of each. I offer an explanation of some long-standing paradoxes in the wellbeing literature and an insight into the links between relative comparisons and loss aversion.ESR

Live Imaging at the Onset of Cortical Neurogenesis Reveals Differential Appearance of the Neuronal Phenotype in Apical versus Basal Progenitor Progeny

The neurons of the mammalian brain are generated by progenitors dividing either at the apical surface of the ventricular zone (neuroepithelial and radial glial cells, collectively referred to as apical progenitors) or at its basal side (basal progenitors, also called intermediate progenitors). For apical progenitors, the orientation of the cleavage plane relative to their apical-basal axis is thought to be of critical importance for the fate of the daughter cells. For basal progenitors, the relationship between cell polarity, cleavage plane orientation and the fate of daughter cells is unknown. Here, we have investigated these issues at the very onset of cortical neurogenesis. To directly observe the generation of neurons from apical and basal progenitors, we established a novel transgenic mouse line in which membrane GFP is expressed from the beta-III-tubulin promoter, an early pan-neuronal marker, and crossed this line with a previously described knock-in line in which nuclear GFP is expressed from the Tis21 promoter, a pan-neurogenic progenitor marker. Mitotic Tis21-positive basal progenitors nearly always divided symmetrically, generating two neurons, but, in contrast to symmetrically dividing apical progenitors, lacked apical-basal polarity and showed a nearly randomized cleavage plane orientation. Moreover, the appearance of beta-III-tubulin–driven GFP fluorescence in basal progenitor-derived neurons, in contrast to that in apical progenitor-derived neurons, was so rapid that it suggested the initiation of the neuronal phenotype already in the progenitor. Our observations imply that (i) the loss of apical-basal polarity restricts neuronal progenitors to the symmetric mode of cell division, and that (ii) basal progenitors initiate the expression of neuronal phenotype already before mitosis, in contrast to apical progenitors

Tis21 Expression Marks Not Only Populations of Neurogenic Precursor Cells but Also New Postmitotic Neurons in Adult Hippocampal Neurogenesis

During embryonic cortical development, expression of Tis21 is associated with cell cycle lengthening and neurogenic divisions of progenitor cells. We here investigated if the expression pattern of Tis21 also correlates with the generation of new neurons in the adult hippocampus. We used Tis21 knock-in mice expressing green fluorescent protein (GFP) and studied Tis21-GFP expression together with markers of adult hippocampal neurogenesis in newly generated cells. We found that Tis21-GFP 1) was absent from the radial glia–like putative stem cells (type-1 cells), 2) first appeared in transient amplifying progenitor cells (type-2 and 3 cells), 3) did not colocalize with markers of early postmitotic maturation stage, 4) was expressed again in maturing neurons, and 5) finally decreased in mature granule cells. Our data show that, in the course of adult neurogenesis, Tis21 is expressed in a phase additional to the one of the embryonic neurogenesis. This additional phase of expression might be associated with a new and different function of Tis21 than during embryonic brain development, where no Tis21 is expressed in mature neurons. We hypothesize that this function is related to the final functional integration of the newborn neurons. Tis21 can thus serve as new marker for key stages of adult neurogenesis

Extinctions, genetic erosion and conservation options for the black rhinoceros (Diceros bicornis)

The black rhinoceros is again on the verge of extinction due to unsustainable poaching in its native range. Despite a wide historic distribution, the black rhinoceros was traditionally thought of as depauperate in genetic variation, and with very little known about its evolutionary history. This knowledge gap has hampered conservation efforts because hunting has dramatically reduced the species’ once continuous distribution, leaving five surviving gene pools of unknown genetic affinity. Here we examined the range-wide genetic structure of historic and modern populations using the largest and most geographically representative sample of black rhinoceroses ever assembled. Using both mitochondrial and nuclear datasets, we described a staggering loss of 69% of the species’ mitochondrial genetic variation, including the most ancestral lineages that are now absent from modern populations. Genetically unique populations in countries such as Nigeria, Cameroon, Chad, Eritrea, Ethiopia, Somalia, Mozambique, Malawi and Angola no longer exist. We found that the historic range of the West African subspecies (D. b. longipes), declared extinct in 2011, extends into southern Kenya, where a handful of individuals survive in the Masai Mara. We also identify conservation units that will help maintain evolutionary potential. Our results suggest a complete re-evaluation of current conservation management paradigms for the black rhinoceros

FRS2α Regulates Erk Levels to Control a Self-Renewal Target Hes1 and Proliferation of FGF-Responsive Neural Stem/Progenitor Cells

Fibroblast growth factor (FGF) is among the most common growth factors used in cultures to maintain self-renewal and proliferative capabilities of a variety of stem cells, including neural stem cells (NSCs). However, the molecular mechanisms underlying the control by FGF have remained elusive. Studies on mutant mice of FGF receptor substrate 2α (FRS2α), a central mediator for FGF signaling, combined with FRS2α knockdown or gain-of-function experiments, allowed us to dissect the role of FGF signaling for the self-renewal and proliferation of NSCs and to provide novel molecular mechanisms for them. We identified Hes1 as a novel self-renewal target of FGF-signaling. Quantitatively different levels of Erk activation mediated by FRS2α may regulate self-renewal of NSCs and proliferation of neural stem/progenitor cells (NSPCs); low levels of Erk activation are sufficient for the former, however, higher levels are required for maximum activity of the latter. Thus, FRS2α fine-tunes the FGF-signaling to control qualitatively different biological activities, self-renewal at least partly through Hes1 versus proliferation of NSPCs. Stem Cells 2010; 28:1661–1673