A mathematical model for top-shelf vertigo: the role of sedimenting otoconia in BPPV

Benign Paroxysmal Positional Vertigo (BPPV) is a mechanical disorder of the vestibular system in which calcite particles called otoconia interfere with the mechanical functioning of the fluid-filled semicircular canals normally used to sense rotation. Using hydrodynamic models, we examine the two mechanisms proposed by the medical community for BPPV: cupulolithiasis, in which otoconia attach directly to the cupula (a sensory membrane), and canalithiasis, in which otoconia settle through the canals and exert a fluid pressure across the cupula. We utilize known hydrodynamic calculations and make reasonable geometric and physical approximations to derive an expression for the transcupular pressure $\Delta P_c$ exerted by a settling solid particle in canalithiasis. By tracking settling otoconia in a two-dimensional model geometry, the cupular volume displacement and associated eye response (nystagmus) can be calculated quantitatively. Several important features emerge: 1) A pressure amplification occurs as otoconia enter a narrowing duct; 2) An average-sized otoconium requires approximately five seconds to settle through the wide ampulla, where $\Delta P_c$ is not amplified, which suggests a mechanism for the observed latency of BPPV; and 3) An average-sized otoconium beginning below the center of the cupula can cause a volumetric cupular displacement on the order of 30 pL, with nystagmus of order $2^\circ$/s, which is approximately the threshold for sensation. Larger cupular volume displacement and nystagmus could result from larger and/or multiple otoconia.Comment: 15 pages, 5 Figures updated, to be published in J. Biomechanic

Optimizing the vertebrate vestibular semicircular canal: could we balance any better?

The fluid-filled semicircular canals (SCCs) of the vestibular system are used by all vertebrates to sense angular rotation. Despite masses spanning seven decades, all mammalian SCCs are nearly the same size. We propose that the SCC represents a sensory organ that evolution has `optimally designed'. Four geometric parameters are used to characterize the SCC, and `building materials' of given physical properties are assumed. Identifying physical and physiological constraints on SCC operation, we find that the most sensitive SCC has dimensions consistent with available data.Comment: 4 pages, 3 figure

A novel class of microRNA-recognition elements that function only within open reading frames.

MicroRNAs (miRNAs) are well known to target 3' untranslated regions (3' UTRs) in mRNAs, thereby silencing gene expression at the post-transcriptional level. Multiple reports have also indicated the ability of miRNAs to target protein-coding sequences (CDS); however, miRNAs have been generally believed to function through similar mechanisms regardless of the locations of their sites of action. Here, we report a class of miRNA-recognition elements (MREs) that function exclusively in CDS regions. Through functional and mechanistic characterization of these 'unusual' MREs, we demonstrate that CDS-targeted miRNAs require extensive base-pairing at the 3' side rather than the 5' seed; cause gene silencing in an Argonaute-dependent but GW182-independent manner; and repress translation by inducing transient ribosome stalling instead of mRNA destabilization. These findings reveal distinct mechanisms and functional consequences of miRNAs that target CDS versus the 3' UTR and suggest that CDS-targeted miRNAs may use a translational quality-control-related mechanism to regulate translation in mammalian cells

Nutrient contamination from non-point sources: Dissolved nitrate and ammonium in surface and subsurface waters at EKU Meadowbrook Farm, Madison County, Kentucky

Agricultural activities often contaminate watersheds with excess nutrients leading to poor water quality and eutrophication. Eastern Kentucky University’s Meadowbrook Farm, contributes dissolved nitrogen into the Muddy Creek watershed. To assess the concentrations of dissolved nitrogen compounds, we sampled waters draining from the Farm as springs, runoff, and subsurface pipe drainage as well as Muddy Creek on six days from May to August 2016 under a variety of weather conditions. We measured dissolved nitrate (NO­3-) and ammonium (NH4+) using standard colorimetric methods and spectrophotometry with an accuracy of ~0.1 mg/L. Nitrate was the dominant nutrient contaminant, whereas ammonium was often absent in water samples. Nitrate levels were usually \u3c2 mg/L in surface waters. Springs and some tributaries exhibited the largest nitrate values generally ranging from 7.0 to 14.3 mg/L. Ammonium displayed sporadic concentration spikes between 2.0 and 4.3 mg/L. Dissolved nitrogen concentrations responded to rainfall. We saw a general decrease of nitrogen concentration during dry periods, especially in Muddy Creek and an increase in nitrogen concentration under wetter conditions. Springs maintained high nitrogen concentrations regardless of different rainfall conditions. We compared our nitrogen measurements from Meadowbrook Farm to national values. For surface waters, the median nitrate concentration was 2.7 mg/L, lower than the national median (3.8 mg/L), whereas ammonium values were 0.2 mg/L, higher than the national median (0.1 mg/L). In groundwater, we found the median nitrate concentration was 3.9 mg/L, higher than the national median (3.4 mg/L), whereas the median ammonium concentration was 0.05 mg/L, higher than the national median (0.02 mg/L)

Geochemical Characteristics and Storm Dynamics of Surface Waters and Groundwater at Eastern Kentucky University’s Meadowbrook Farm, Madison County, Kentucky

Agricultural activities often contaminate watersheds with excess nutrients leading to poor water quality and eutrophication. Eastern Kentucky University’s Meadowbrook Farm raises crops and livestock, contributing dissolved nutrients to the neighboring Muddy Creek watershed. Consequently, the Farm is developing methods to sequester and limit nutrient contamination. Before phosphorous sequestration methods can be tested, the geochemistry of surface water and groundwater on the Farm need to be better understood to determine hydrological pathways. We use naturally-occurring, dissolved cations as tracers to identify the contribution of different water sources and interpret storm events. Water samples taken from springs (groundwater), surface water, and storm water on the Farm were analyzed for dissolved cations via ICP-OES for sodium (Na+), potassium (K+), calcium (Ca2+), and magnesium (Mg2+). A V-notch weir was used to quantify volumetric flow for a rain event during tropical storm Cindy. Ca2+ and Mg2+ concentrations (55.5-80.0 mg/L and 21.7-32.5 mg/L, respectively) and lower Na+ and K+ concentrations (9.6-14.8 mg/L and 1.7-18.3 mg/L, respectively) seem to predominantly characterize source groundwater. During Cindy, Ca2+, Mg2+, and Na+ decreased with increasing volumetric flow rate, likely indicating dilution of groundwater. However, K+ exhibited elevated concentrations that spike concurrently with initial discharge peaks and then progressively decrease over the duration of the storm event. We hypothesize that initial K+ increases represent significant overland flow followed by dilution with groundwater and/or continued runoff. If nutrient runoff behavior is similar to potassium, those nutrients should exhibit peak export with initial runoff

Natural Selection For Environmentally Induced Phenotypes In Tadpoles

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137452/1/evo05119.pd

Characterization of groundwater and surface water geochemistry in an agricultural setting at EKU Meadowbrook Farm, Madison County, Kentucky

Agricultural activities often contaminate watersheds with excess nutrients leading to poor water quality and eutrophication. Eastern Kentucky University (EKU) Meadowbrook Farm raises crops and livestock, which contribute dissolved nutrients to the neighboring Muddy Creek watershed. Consequently, the Farm is developing methods to sequester phosphorous and limit nutrient contamination. Before phosphorous sequestration methods can be tested, Farm surface water and groundwater geochemistry must be better understood to determine hydrological pathways for nutrients. We use naturally-occurring dissolved cations, pH, oxidation-reduction potential (ORP), specific conductivity (SC), dissolved oxygen (DO%), total hardness, and alkalinity as chemical tracers to parse the contribution of dissolved ions from different water sources, to recognize different water source chemistries, and to interpret storm events. To measure discharge from a proximal, intermittent stream that drains a representative and critical portion of the Farm, we used an instrumented, V-notch weir to examine storm-water flow during Tropical Storm Cindy (June 22-25, 2017). Water samples taken from springs (groundwater), surface water, and storm water on the Farm were analyzed for various dissolved constituents. Dissolved cations were measured via ICP-OES (ACT Labs) for sodium (Na+), potassium (K+), calcium (Ca2+), and magnesium (Mg2+). pH, ORP, SC, and DO% were determined with YSI and Vernier probes. Alkalinity and total hardness were measured via the bromocresol green - methyl red and the EDTA digital titration methods, respectively. Dissolved ammonium (NH4+), nitrate (NO3-), and phosphate (PO43-) concentrations were determined by colorimetry with a UV-VIS spectrophotometer via the sodium hypochlorite, cadmium reduction, and ascorbic acid methods, respectively. Both groundwater and surface water sources exhibit similar ranges of pH (neutral to basic), ORP (oxidizing), alkalinity, total hardness, DO%, and SC. Source waters generally have high Ca2+ and Mg2+, and low K+, Na+, PO43-, and NH4+ concentrations. This strongly suggests that background chemistries of source groundwater and surface water are controlled by local limestone bedrock dissolution. Groundwater is further characterized by relatively high NO3- concentrations and low temperatures; in contrast, surface waters exhibit higher temperatures and lower NO3- concentrations. During the Cindy event, concentration of Ca2+, Mg2+, and Na+ within baseline source waters decreased with increasing discharge through the weir (Fig. 1), along with SPC, pH, and alkalinity. This behavior represents dilution of Farm groundwater by storm precipitation and subsequent overland flow. However, K+ increased from baseline concentrations, spiking concurrently with increased discharge through the weir, and then progressively decreased in magnitude over the duration of the storm (Fig. 2). These data suggest that K+ was flushed from soil by rain waters. Nutrient concentrations increase with increased discharge indicating transport by surface runoff. For example, PO43- concentrations closely track and are proportional to discharge, which suggests PO43- transport from the surficial soil substrate via flushing by precipitation (Fig. 3). NO3- exhibited nearly identical transport behavior as K+; concentration spikes occur simultaneously with K+ and discharge. However, NO3- levels reached a higher baseline concentration than pre-storm levels. The Cindy event suggests infiltration and retention of NO3- within soil and groundwater during fair weather, initial flushing during the rain event, and then prolonged NO3- release from Farm soil and groundwater. Background concentration of NH4+ is generally 0.0 to 0.2 mg/L. Immediately prior to water flow over the weir during the Cindy event, concentrations were unusually high (~1.7 mg/L). During the first storm pulse, these high concentrations decreased significantly to \u3c0.4 mg/L. Later in the main storm event, NH4+ tracked discharge from the weir and afterward returned to typical background concentrations. This behavior suggests rapid release of NH4+ from soil followed by accumulation within the weir pool and then subsequent flushing during the precipitation event

Pigmentation plasticity enhances crypsis in larval newts: Associated metabolic cost and background choice behaviour

In heterogeneous environments, the capacity for colour change can be a valuable adaptation enhancing crypsis against predators. Alternatively, organisms might achieve concealment by evolving preferences for backgrounds that match their visual traits, thus avoiding the costs of plasticity. Here we examined the degree of plasticity in pigmentation of newt larvae (Lissotriton boscai) in relation to predation risk. Furthermore, we tested for associated metabolic costs and pigmentation-dependent background choice behaviour. Newt larvae expressed substantial changes in pigmentation so that light, high-reflecting environment induced depigmentation whereas dark, low-reflecting environment induced pigmentation in just three days of exposure. Induced pigmentation was completely reversible upon switching microhabitats. Predator cues, however, did not enhance cryptic phenotypes, suggesting that environmental albedo induces changes in pigmentation improving concealment regardless of the perceived predation risk. Metabolic rate was higher in heavily pigmented individuals from dark environments, indicating a high energetic requirement of pigmentation that could impose a constraint to larval camouflage in dim habitats. Finally, we found partial evidence for larvae selecting backgrounds matching their induced phenotypes. However, in the presence of predator cues, larvae increased the time spent in light environments, which may reflect a escape response towards shallow waters rather than an attempt at increasing crypsisFinancial support was provided by the Spanish Ministry of Science and Innovation (MICINN), Grant CGL2012-40044 to IGM, and by the Universidad Autónoma de Madrid, Short Stay Grant to NPC. Additional financial support was provided by the MICINN, Grant CGL2015-68670-R to NP

Vms1 and ANKZF1 peptidyl-tRNA hydrolases release nascent chains from stalled ribosomes

Ribosomal surveillance pathways scan for ribosomes that are transiently paused or terminally stalled owing to structural elements in mRNAs or nascent chain sequences. Some stalls in budding yeast are sensed by the GTPase Hbs1, which loads Dom34, a catalytically inactive member of the archaeo-eukaryotic release factor 1 superfamily. Hbs1–Dom34 and the ATPase Rli1 dissociate stalled ribosomes into 40S and 60S subunits. However, the 60S subunits retain the peptidyl-tRNA nascent chains, which recruit the ribosome quality control complex that consists of Rqc1–Rqc2–Ltn1–Cdc48–Ufd1–Npl4. Nascent chains ubiquitylated by the E3 ubiquitin ligase Ltn1 are extracted from the 60S subunit by the ATPase Cdc48–Ufd1–Npl4 and presented to the 26S proteasome for degradation. Failure to degrade the nascent chains leads to protein aggregation and proteotoxic stress in yeast and neurodegeneration in mice. Despite intensive investigations on the ribosome quality control pathway, it is not known how the tRNA is hydrolysed from the ubiquitylated nascent chain before its degradation. Here we show that the Cdc48 adaptor Vms1 is a peptidyl-tRNA hydrolase. Similar to classical eukaryotic release factor 1, Vms1 activity is dependent on a conserved catalytic glutamine. Evolutionary analysis indicates that yeast Vms1 is the founding member of a clade of eukaryotic release factor 1 homologues that we designate the Vms1-like release factor 1 clade

Dissolved phosphate concentrations in surface water and groundwater at EKU’s Meadowbrook Farm, Madison County, Kentucky

Farms are non-point sources for nutrient contaminants that drain into watersheds and contribute to eutrophication and other environmental problems. EKU’s Meadowbrook Farm raises both crops and livestock, causing dissolved phosphorus in the form of orthophosphate (PO43-) to enter surface and subsurface waters, eventually flowing into the Muddy Creek watershed. We sampled springs, French drains, surface water from the farm, and Muddy Creek waters from May through August 2016. Typically 1 to 2 days after sampling, we measured orthophosphate concentration using the established ascorbic acid method and a UV-VIS spectrophotometer with general accuracy and precision of ~0.1 mg/L, or ppm. Phosphate concentrations are generally low when compared to nitrate usually ranging from 0 to 0.2 mg/L P-PO4 with higher concentrations of 0.5 to 2.7 mg/L P-PO4 occurring sporadically. With minor exceptions, we saw little difference in phosphate concentration between different sample sources whether spring water, water from subsurface drains, surface waters flowing over the Farm, or Muddy Creek waters. For example, one sub-watershed draining the Farm had increased levels of phosphate on 24 May (2.7 mg/L) and on 24 June (0.5 mg/L), immediately following a significant rain event. However, overall patterns of phosphate concentration were similar whether sampling during periods with little or no rainfall, or periods following rain events. In summary, phosphate export from the Farm is apparently low, but more systematic sampling in the future may reveal heretofore unrecognized patterns