Cochlear hair cell fate determination and differentiation in vitro

Mammalian cochlear hair cells are relatively inaccessible and few in number. This hampers any research on their fate determination and differentiation. The production of conditionally immortal cell lines from the H2KbtsA58 transgenic mouse should overcome these difficulties. The aims of the present study were threefold. Firstly, to establish that the cell lines provide a viable in vitro system, by examining the pattern of molecular expression in the cochlear hair cell line UB/OC-1. Secondly, to examine differentiation by using clonal derivatives from the heterogeneous cell line UB/OC-l. Thirdly, to explore the process of lateral specification in the determination of cell fate and to explain the differentiation of hair cells and supporting cells from a common precursor. The methods used were cell culture, immunocytochemistry, reverse transcription polymerase chain reaction and western blot. The results demonstrated that firstly; the temporal expression pattern of Brn3.1, an essential transcription factor required for hair cell differentiation, and the a9 subunit of the nicotinic acetylcholine receptor, followed a similar pattern to that during normal development. Secondly, epithelial cell markers such as, vimentin, cytokeratin, actin and cadherin, and specific hair cell markers such as myosinVIIA and fimbrin were expressed when the hair cells differentiated. The pattern of expression suggested parallel pathways of gene expression during differentiation of hair cells. Thirdly, from the expression of Numblike, Notch 1, Jagged I and Jagged2, factors which are known to be involved in lateral specification, a model is proposed to explain hair cell fate determination. The results also demonstrate the much greater experimental flexibility offered by cell lines in understanding hair cell development. Future studies will focus on functional experiments that alter hair cell fate

Washington\u27s War on the Visibly Poor: A Survey of Criminalizing Ordinances & Their Enforcement

Throughout the country, cities increasingly enact laws that punish behaviors necessary for survival. For those without shelter, there is no alternative but to conduct these behaviors in public. Camping outdoors, sleeping, going to the bathroom, receiving food, sitting or lying down on sidewalks — these laws target homeless people either in practice or outright. But until now, no one knew how widespread these laws are throughout Washington State, or how they are being enforced. This brief answers these questions. HRAP researchers surveyed the municipal codes of seventy-two cities across Washington to identify ordinances that essentially criminalize homelessness in each jurisdiction. From this survey, researchers created a chart tracking every ordinance they could find. Seven of the cities were selected as case studies for closer examination of the enforcement and citations of these ordinances. The findings reveal that homeless criminalization exists regardless of where you live. From densely populated urban cities to scattered rural townships, city councils are increasingly passing these laws, often drafting them in a way that raises serious legal and policy concerns about how Washington treats its most vulnerable residents. This brief shines a spotlight on the problems with these laws: how they are written, how they impact the homeless community, and how easily cities can fall into the trap of vilifying already vulnerable populations in the name of safety and public health. This report shows that the problem of criminalizing homelessness, so often buried in municipal codes, is both widespread and systemic. Keywords: public space, homelessness, race, gender, sexual orientation, sexual identity, LGBTQ, homeless, poverty, constitutional rights, civil rights, human rights, criminalization, neolibera

Thermally-Assisted Current-Driven Domain Wall Motion

Starting from the stochastic Landau-Lifschitz-Gilbert equation, we derive Langevin equations that describe the nonzero-temperature dynamics of a rigid domain wall. We derive an expression for the average drift velocity of the domain wall as a function of the applied current, and find qualitative agreement with recent magnetic semiconductor experiments. Our model implies that at any nonzero temperature the average domain-wall velocity initially varies linearly with current, even in the absence of non-adiabatic spin torques.Comment: 4 pages, 2 figure

The Ten Stone Ranges Structural Complex of the central Mackenzie Mountains fold-and-thrust belt: a structural analysis with implications on the Plateau Fault and regional detachment level

The Cordilleran Orogen affected majority of the western margin of ancient continental North America in the Cretaceous, which is well recorded in the Foreland Belt. The Mackenzie Mountains fold-and-thrust belt is located primarily in the westernmost Northwest Territories and easternmost Yukon Territory in northern Canada. The mountains are often described as the northern extension of the Rocky Mountains to the south which are one of the world’s best examples of a thin-skinned fold-and-thrust belt. Within the Mackenzie Mountains, Neo-Proterozoic through Cretaceous sedimentary rocks record the Laramide aged deformation, with a range of structures that vary in size and complexity. Previous mapping by the Geological Survey of Canada produced a series of reconnaissance maps that are still in use today, many of which are available in only black and white. This study is focused on a part of the 1:250 000 scale NTS 106A Mount Eduni map sheet from Geological Survey of Canada reconnaissance mapping in 1974. The study involved re-mapping a large panel at 1:50 000 scale to better understand the structural geometry, regional shortening and the depth of the underlying detachment level. Through systematic geologic mapping and structural analyses, this study presents a balanced regional cross-section, numerous serial cross-sections and a detailed geologic map of the study area, the Ten Stone Ranges Structural Complex. The serial cross-sections were used to define the geometry of the Cache Lake Fold, a large fault-bend-fold system that involves a folded thrust fault and complicated subsurface geometry. In addition to this, the sections confirmed that the TSRSC is a transfer zone whereby a series of thrust faults and décollement folds are responsible for much of the displacement and shortening in the Mount Eduni map sheet. The balanced regional cross-section was constructed across a number of key structural elements, in particular the Plateau Fault, a regional structure with a > 250 kilometer strike length and the subject of much debate as to its geometry. In addition to this structure, the cross-section transects the Cache Lake Fold and the Shattered Range Anticline, a regional box shaped anticline that was used for a “depth to detachment” calculation. By examining the regional detachment level estimated from the balanced cross-section and calculating the detachment depth using the Shattered Range Anticline the detachment depth was found to be – 11.3 kilometers below the current erosional level. This study is the first structural analyses of the Mount Eduni map sheet, particularly the Ten Stone Ranges Structural Complex, and has resulted in an estimate of the detachment depth for the area, a shortening estimate of > 7 kilometers across the 50 kilometer line of section and a displacement estimate for the Plateau Thrust of > 20 kilometers

Unexpected reductions in regional cerebral perfusion during prolonged hypoxia

KEY POINTS: Cognitive performance is impaired by hypoxia despite global cerebral oxygen delivery and metabolism being maintained. Using arterial spin labelled (ASL) magnetic resonance imaging, this is the first study to show regional reductions in cerebral blood flow (CBF) in response to decreased oxygen supply (hypoxia) at 2 h that increased in area and became more pronounced at 10 h. Reductions in CBF were seen in brain regions typically associated with the ‘default mode’ or ‘task negative’ network. Regional reductions in CBF, and associated vasoconstriction, within the default mode network in hypoxia is supported by increased vasodilatation in these regions to a subsequent hypercapnic (5% CO(2)) challenge. These results suggest an anatomical mechanism through which hypoxia may cause previously reported deficits in cognitive performance. ABSTRACT: Hypoxia causes an increase in global cerebral blood flow, which maintains global cerebral oxygen delivery and metabolism. However, neurological deficits are abundant under hypoxic conditions. We investigated regional cerebral microvascular responses to acute (2 h) and prolonged (10 h) poikilocapnic normobaric hypoxia. We found that 2 h of hypoxia caused an expected increase in frontal cortical grey matter perfusion but unexpected perfusion decreases in regions of the brain normally associated with the ‘default mode’ or ‘task negative’ network. After 10 h in hypoxia, decreased blood flow to the major nodes of the default mode network became more pronounced and widespread. The use of a hypercapnic challenge (5% CO(2)) confirmed that these reductions in cerebral blood flow from hypoxia were related to vasoconstriction. Our findings demonstrate steady‐state deactivation of the default network under acute hypoxia, which become more pronounced over time. Moreover, these data provide a unique insight into the nuanced localized cerebrovascular response to hypoxia that is not attainable through traditional methods. The observation of reduced perfusion in the posterior cingulate and cuneal cortex, which are regions assumed to play a role in declarative and procedural memory, provides an anatomical mechanism through which hypoxia may cause deficits in working memory

Precise determination of critical exponents and equation of state by field theory methods

Renormalization group, and in particular its Quantum Field Theory implementation has provided us with essential tools for the description of the phase transitions and critical phenomena beyond mean field theory. We therefore review the methods, based on renormalized phi^4_3 quantum field theory and renormalization group, which have led to a precise determination of critical exponents of the N-vector model (R. Guida and J. Zinn-Justin, J. Phys. A31 (1998) 8103. cond-mat/9803240). and of the equation of state of the 3D Ising model (R. Guida and J. Zinn-Justin, Nucl. Phys. B489 [FS] (1997) 626, hep-th/9610223.). These results are among the most precise available probing field theory in a non-perturbative regime.Comment: 23 pages, tex, private macros, one figur

Towards Factory location planning using GIS

Today, companies face continuously increasing competitive pressure resulting from highly volatile markets, globalisation and constantly growing customer requirements. Against this background, the location of a factory has a significant influence on competitiveness. The process of location planning is crucial for future success, as the choice of location can determine competitive aspects such as the distance to customers and suppliers or the attractiveness for employees for decades. At present, location decisions are often derived heuristically by gradually narrowing down the object of consideration starting from the global level. In the future, geo-information systems (GIS) shall help to make a more holistic and future-proof factory location decision, which is less dependent on subjective feelings and takes less time and costs. In this paper, the necessary fundamentals for factory location planning with GIS are presented, and it is explained which factory planning information can support location planning using GIS

Relating functional and structural signatures of Parkinson’s disease to changes in dopamine signalling: A PET/fMRI study

Cognitive impairments in early Parkinson\u27s disease are known to be linked to complex changes in the dopamine system within the brain. For example, dopamine-producing neurons in one key region of the brain are significantly degenerated, but those in another are spared. Dopamine-replacement therapy (DRT) has been pursued and it has produced significant improvements in certain cognitive functions - unfortunately it also produced significant impairments in others.https://ir.lib.uwo.ca/brainscanprojectsummaries/1019/thumbnail.jp

Sedimentary talc in Neoproterozoic carbonate successions

Mineralogical, petrographic and sedimentological observations document early diagenetic talc in carbonate-dominated successions deposited on two early Neoproterozoic (~ 800–700 million years old) platform margins. In the Akademikerbreen Group, Svalbard, talc occurs as nodules that pre-date microspar cements that fill molar tooth structures and primary porosity in stromatolitic carbonates. In the upper Fifteenmile Group of the Ogilvie Mountains, NW Canada, the talc is present as nodules, coated grains, rip-up clasts and massive beds that are several meters thick. To gain insight into the chemistry required to form early diagenetic talc, we conducted precipitation experiments at 25 °C with low-SO4 synthetic seawater solutions at varying pH, Mg2+ and SiO2(aq). Our experiments reveal a sharp and reproducible pH boundary (at ~ 8.7) only above which does poorly crystalline Mg-silicate precipitate; increasing Mg2+ and/or SiO2(aq) alone is insufficient to produce the material. The strong pH control can be explained by Mg-silica complexing activated by the deprotonation of silicic acid above ~ 8.6–8.7. FT-IR, TEM and XRD of the synthetic precipitates reveal a talc-like 2:1 trioctahedral structure with short-range stacking order. Hydrothermal experiments simulating burial diagenesis show that dehydration of the precipitate drives a transition to kerolite (hydrated talc) and eventually to talc. This formation pathway imparts extensive layer stacking disorder to the synthetic talc end-product that is identical to Neoproterozoic occurrences. Early diagenetic talc in Neoproterozoic carbonate platform successions appears to reflect a unique combination of low Al concentrations (and, by inference, low siliciclastic input), near modern marine salinity and Mg2+, elevated SiO2(aq), and pH > ~ 8.7. Because the talc occurs in close association with microbially influenced sediments, we suggest that soluble species requirements were most easily met through microbial influences on pore water chemistry, specifically pH and alkalinity increases driven by anaerobic Fe respiration.Organismic and Evolutionary Biolog