Development of the stria vascularis and potassium regulation in the human fetal cochlea : insights into hereditary sensorineural hearing loss

Sensorineural hearing loss (SNHL) is one of the most common congenital disorders in humans, afflicting one in every thousand newborns. The majority is of heritable origin and can be divided in syndromic and nonsyndromic forms. Knowledge of the expression profile of affected genes in the human fetal cochlea is limited, and as many of the gene mutations causing SNHL likely affect the stria vascularis or cochlear potassium homeostasis (both essential to hearing), a better insight into the embryological development of this organ is needed to understand SNHL etiologies. We present an investigation on the development of the stria vascularis in the human fetal cochlea between 9 and 18 weeks of gestation (W9–W18) and show the cochlear expression dynamics of key potassium‐regulating proteins. At W12, MITF+/SOX10+/KIT+ neural‐crest‐derived melanocytes migrated into the cochlea and penetrated the basement membrane of the lateral wall epithelium, developing into the intermediate cells of the stria vascularis. These melanocytes tightly integrated with Na(+)/K(+)‐ATPase‐positive marginal cells, which started to express KCNQ1 in their apical membrane at W16. At W18, KCNJ10 and gap junction proteins GJB2/CX26 and GJB6/CX30 were expressed in the cells in the outer sulcus, but not in the spiral ligament. Finally, we investigated GJA1/CX43 and GJE1/CX23 expression, and suggest that GJE1 presents a potential new SNHL associated locus. Our study helps to better understand human cochlear development, provides more insight into multiple forms of hereditary SNHL, and suggests that human hearing does not commence before the third trimester of pregnancy. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 1219–1240, 201

Spectral induced polarization (SIP) of denitrification‐driven microbial activity in column experiments packed with calcareous aquifer sediments

Spectral Induced Polarization (SIP) has been suggested as a non-invasive monitoring proxy for microbial processes. Under natural conditions, however, multiple and often coupled polarization processes co-occur, impeding the interpretation of SIP signals. In this study, we analyze the sensitivity of SIP to microbially-driven reactions under quasi-natural conditions. We conducted flow-through experiments in columns equipped with SIP electrodes and filled with natural calcareous, organic-carbon-rich aquifer sediment, in which heterotrophic denitrification was bio-stimulated. Our results show that, even in the presence of parallel polarization processes in a natural sediment under field-relevant geochemical conditions, SIP is sufficiently sensitive to microbially-driven changes in electrical charge storage. Denitrification yielded an increase in imaginary conductivity of up to 3.1 μS cm -1 (+140%) and the formation of a distinct peak between 1 and 10 Hz, that matched the timing of expected microbial activity predicted by a reactive transport model fitted to solute concentrations. A Cole-Cole decomposition allowed separating the polarization contribution of microbial activity from that of cation exchange, thereby helping to locate microbial hotspots without the need for (bio)geochemical data to constrain the Cole-Cole parameters. Our approach opens new avenues for the application of SIP as a rapid method to monitor a system's reactivity in situ. While in preceding studies the SIP signals of microbial activity in natural sediments were influenced by mineral precipitation/dissolution reactions, the imaginary conductivity changes measured in the biostimulation experiments presented here were dominated by changes in the polarization of the bacterial cells rather than a reaction-induced alteration of the abiotic matrix.Baden‐Württemberg StiftungGerman Research Foundation DFGProjekt DEA

Cognitive radio network in vehicular ad hoc network (VANET): a survey

Cognitive radio network and vehicular ad hoc network (VANET) are recent emerging concepts in wireless networking. Cognitive radio network obtains knowledge of its operational geographical environment to manage sharing of spectrum between primary and secondary users, while VANET shares emergency safety messages among vehicles to ensure safety of users on the road. Cognitive radio network is employed in VANET to ensure the efficient use of spectrum, as well as to support VANET’s deployment. Random increase and decrease of spectrum users, unpredictable nature of VANET, high mobility, varying interference, security, packet scheduling, and priority assignment are the challenges encountered in a typical cognitive VANET environment. This paper provides survey and critical analysis on different challenges of cognitive radio VANET, with discussion on the open issues, challenges, and performance metrics for different cognitive radio VANET applications

Using relative and absolute measures for monitoring health inequalities: experiences from cross-national analyses on maternal and child health

Background. As reducing socio-economic inequalities in health is an important public health objective, monitoring of these inequalities is an important public health task. The specific inequality measure used can influence the conclusions drawn, and there is no consensus on which measure is most meaningful. The key issue raising most debate is whether to use relative or absolute inequality measures. Our paper aims to inform this debate and develop recommendations for monitoring health inequalities on the basis of empirical analyses for a broad range of developing countries. Methods. Wealth-group specific data on under-5 mortality, immunisation coverage, antenatal and delivery care for 43 countries were obtained from the Demographic and Health Surveys. These data were used to describe the association between the overall level of these outcomes on the one hand, and relative and absolute poor-rich inequalities in these outcomes on the other. Results. We demonstrate that the values that the absolute and relative inequality measures can take are bound by mathematical ceilings. Yet, even where these ceilings do not play a role, the magnitude of inequality is correlated with the overall level of the outcome. The observed tendencies are, however, not necessities. There are countries with low mortality levels and low relative inequalities. Also absolute inequalities showed variation at most overall levels. Conclusion. Our study shows that both absolute and relative inequality measures can be meaningful for monitoring inequalities, provided that the overall level of the outcome is taken into account. Suggestions are given on how to do this. In addition, our paper presents data that can be used for benchmarking of inequalities in the field of maternal and child health in low and middle-income countries

Multimodal imaging of hair follicle bulge-derived stem cells in a mouse model of traumatic brain injury

Traumatic brain injury (TBI) is a devastating event for which current therapies are limited. Stem cell transplantation may lead to recovery of function via different mechanisms, such as cell replacement through differentiation, stimulation of angiogenesis and support to the microenvironment. Adult hair follicle bulge-derived stem cells (HFBSCs) possess neuronal differentiation capacity, are easy to harvest and are relatively immune-privileged, which makes them potential candidates for autologous stem cell-based therapy. In this study, we apply in vivo multimodal, optical and magnetic resonance imaging techniques to investigate the behavior of mouse HFBSCs in a mouse model of TBI. HFBSCs expressed Luc2 and copGFP and were examined for their differentiation capacity in vitro. Subsequently, transduced HFBSCs, preloaded with ferumoxytol, were transplanted next to the TBI lesion (cortical region) in nude mice, 2 days after injury. Brains were fixed for immunohistochemistry 58 days after transplantation. Luc2- and copGFP-expressing, ferumoxytol-loaded HFBSCs showed adequate neuronal differentiation potential in vitro. Bioluminescence of the lesioned brain revealed survival of HFBSCs and magnetic resonance imaging identified their localization in the area of transplantation. Immunohistochemistry showed that transplanted cells stained for nestin and neurofilament protein (NF-Pan). Cells also expressed laminin and fibronectin but extracellular matrix masses were not detected. After 58 days, ferumoxytol could be detected in HFBSCs in brain tissue sections. These results show that HFBSCs are able to survive after brain transplantation and suggest that ce

SIP an Biokohlen - Neue Ergebnisse und neue Einsichten in das elektrochemische Modell von Wong (Geophysics 1979, 44(7), 1245-1265)

Biokohlen unterscheiden sich je nach Ausgangsmaterial und Herstellungsverfahren mitunter beträchtlich. Bei den Herstellungsverfahren kann man im Wesentlichen drei Typen unterscheiden. Die Pyrolyse, d.h. die Erhitzung auf 300-800 °C unter Sauerstoffausschluss, die Vergasung, d.h. die Erhitzung unter Zusatz eines Oxidationsmittels im Unterschuss vorwiegend bei noch höheren Temperaturen und die hydrothermale Karbonisierung. Letztere findet im Gegensatz zu den ersten beiden im Kontakt des zu karbonisierenden Materials mit einer Wasserphase unter Druck bei Temperaturen von 150-300 °C statt. Die Produkte der hydrothermalen Karbonisierung unterscheiden sich deshalb beträchtlich von denen der beiden anderen Verfahrenstypen. Die hydrothermale Karbonisierung ist besonders vorteilhaft, wenn das Ausgangsmaterial eine hohe Feuchte hat und bei den anderen beiden Verfahren viel Energie verbraucht wird, um die Feuchte aus dem Material auszutreiben. In diesem Beitrag werden die Ergebnisse aus der Bestimmung oberflächenfunktioneller Gruppen durch Boehm-Titration und elektrischer Messungen mit spektraler induzierter Polarisation (SIP) für eine pyrolytische Kohle aus Kiefernholz und einer Kohle aus der hydrothermalen Karbonisierung von Miscanthus giganteus (Elefantengras) verglichen. Die Kohle aus der hydrothermalen Karbonisierung enthält deutlich mehr funktionelle Gruppen, zeigt aber nur eine relativ geringe elektrische Polarisation in wassergesättigten Mischungen mit Sand. Die pyrolytische Kohle, die mit einer langen Kontaktzeit bei 400 °C hergestellt worden war, zeigt dagegen eine sehr hohe Polarisation und im Gegensatz zu der anderen Kohle keine Abhängigkeit des Phasenwinkels vom Elektrolytgehalt des Wassers. Daraus kann geschlossen werden, dass der Polarisationsmechanismus für beide Kohlen unterschiedlich ist. Während bei der Kohle aus der hydrothermalen Karbonisierung im Wesentlichen eine Polarisation durch Verschiebung der Ionen in der elektrischen Doppelschicht stattfindet, erfolgt bei der pyrolytischen Kohle eine Polarisation der Elektronenverteilung in den elektronisch leitenden Kohlepartikeln. Die SIP-Spektren solcher Materialien lassen sich mit der Theorie von Wong beschreiben, welche die Leckströme durch Redox-Reaktionen über die Partikel-Elektrolyt-Grenzfläche mitberücksichtigt. Die Messwerte für die Kohle aus Kiefernholz lassen sich bei Verwendung sinnvoller Parameter mit dieser Theorie recht gut beschreiben, wenn man in Betracht zieht, dass einige der Voraussetzungen der Theorie nicht erfüllt sind. Elektronenmikroskopische Aufnahmen zeigen, dass die pyrolytische Kohle eine hohe Porosität besitzt, weswegen die Kontaktfläche mit dem Elektrolyt verglichen mit der Kontaktfläche starrer Kugeln, wie sie die Theorie voraussetzt, wesentlich größer wird. Deshalb muss ein wesentlich höherer Volumenanteil an Kohle in das theoretische Modell eingesetzt werden, um die gemessene Peakhöhe des Phasenwinkels zu erhalten. Eine Weiterentwicklung der Theorie von Wong wäre deshalb anzustreben

Neuronal differentiation of hair-follicle-bulge-derived stem cells co-cultured with mouse cochlear modiolus explants

Stem-cell-based repair of auditory neurons may represent an attractive therapeutic option to restore sensorineural hearing loss. Hair-follicle-bulge-derived stem cells (HFBSCs) are promising candidates for this type of therapy, because they (1) have migratory properties, enabling migration after transplantation, (2) can differentiate into sensory neurons and glial cells, and (3) can easily be harvested in relatively high numbers. However, HFBSCs have never been used for this purpose. We hypothesized that HFBSCs can be used for cell-based repair of the auditory nerve and we have examined their migration and incorporation into cochlear modiolus explants and their subsequent differentiation. Modiolus explants obtained from adult wild-type mice were cultured in the presence of EF1α-copGFP-transduced HFBSCs, constitutively expressing copepod green fluorescent protein (copGFP). Also, modiolus explants without hair cells were co-cultured with DCX-copGFP-transduced HFBSCs, which demonstrate copGFP upon doublecortin expression during neuronal differentiation. Velocity of HFBSC migration towards modiolus explants was calculated, and after two weeks, co-cultures were fixed and processed for immunohistochemical staining. EF1α-copGFP HFBSC migration velocity was fast: 80.5 ± 6.1 μm/h. After arrival in the explant, the cells formed a fascicular pattern and changed their phenotype into an ATOH1-positive neuronal cell type. DCX-copGFP HFBSCs became green-fluorescent after integration into the explants, confirming neuronal differentiation of the cells. These results show that HFBSC-derived neuronal progenitors are migratory and can integrate into cochlear modiolus explants, while adapting their phenotype depending on this micro-environment. Thus, HFBSCs show potential to be employed in cell-based therapies for auditory nerve repair

Transitions across cognitive states and death among older adults in relation to education:A multistate survival model using data from six longitudinal studies

INTRODUCTION: This study examines the role of educational attainment, an indicator of cognitive reserve, on transitions in later life between cognitive states (normal Mini-Mental State Examination (MMSE), mild MMSE impairment, and severe MMSE impairment) and death. METHODS: Analysis of six international longitudinal studies was performed using a coordinated approach. Multistate survival models were used to estimate the transition patterns via different cognitive states. Life expectancies were estimated. RESULTS: Across most studies, a higher level of education was associated with a lower risk of transitioning from normal MMSE to mild MMSE impairment but was not associated with other transitions. Those with higher levels of education and socioeconomic status had longer nonimpaired life expectancies. DISCUSSION: This study highlights the importance of education in later life and that early life experiences can delay later compromised cognitive health. This study also demonstrates the feasibility and benefit in conducting coordinated analysis across multiple studies to validate findings