Differences In Relative Levels Research Articles

Interleukin-1beta and inflammasome expression in spinal cord following chronic constriction injury in male and female rats

Females represent a majority of chronic pain patients and show greater inflammatory immune responses in human chronic pain patient populations as well as in animal models of neuropathic pain. Recent discoveries in chronic pain research have revealed sex differences in inflammatory signaling, a key component of sensory pathology in chronic neuropathic pain, inviting more research into the nuances of these sex differences. Here we use the chronic constriction injury (CCI) model to explore similarities and differences in expression and production of Inflammatory cytokine IL-1beta in the lumbar spinal cord, as well as its role in chronic pain. We have discovered that intrathecal IL-1 receptor antagonist reverses established pain in both sexes, and increased gene expression of inflammasome NLRP3 is specific to microglia and astrocytes rather than neurons, while IL-1beta is specific to microglia in both sexes. We report several sex differences in the expression level of the genes coding for IL-1beta, as well as the four inflammasomes responsible for IL-1beta release: NLRP3, AIM2, NLRP1, and NLRC4 in the spinal cord. Total mRNA, but not protein expression of IL-1beta is greater in females than males after CCI. Also, while CCI increases all four inflammasomes in both sexes, there are sex differences in relative levels of inflammasome expression. NLRP3 and AIM2 are more highly expressed in females, whereas NLRP1 expression is greater in males.

Особенности ролевой самооценки российских и китайских студентов

This paper meets the need for cross-cultural research into the role aspects of university student behaviour against the background of increasing academic migration. Students that adhere to different cultural patterns may have a different understanding of various situations arising in the teaching process and a different perception of their social role in such situations. The article analyses the level-related and structural differences in the aspects of role self-assessment depending on the socio-cultural context. The authors use the method of S. Schwartz (PVQ-40) and the authors’ questionnaire aimed at identifying the aspects of role self-assessment. The study involved 300 respondents, including 185 Chinese and 115 Russian students. We formulated a hypothesis that students from cultures which differ in terms of the “collectivism-individualism” criterium show level-related and structural differences in the aspects of role self-esteem. The analysis of value profiles allows us to establish that Chinese students are more committed to the values of collectivism compared to Russians. The aspects of role self-assessment in the two groups do not have level-related differences—however, students from China demonstrate higher self-assessments of role typicality, and it is also more important for them to meet the expectations of status reference figures—i. e., parents, teachers, and representatives of the university administration. Based on the analysis of structural differences, it is shown that perceived role typicality is an important factor of positive role self-esteem for the Chinese sample, which probably determines a greater social normativity, including in academic behaviour. Further studies of students’ role self-esteem can be aimed at correlating its structure with the motivation for academic achievements and the peculiarities of the cultural identity of students from different countries.

Effect of AQP Inhibition on Boar Sperm Cryotolerance Depends on the Intrinsic Freezability of the Ejaculate.

Aquaporins (AQPs) are transmembrane channels with permeability to water and small solutes that can be classified according to their structure and permeability into orthodox AQPs, aquaglyceroporins (GLPs), and superAQPs. In boar spermatozoa, AQPs are related to osmoregulation and play a critical role in maturation and motility activation. In addition, their levels differ between ejaculates with good and poor cryotolerance (GFE and PFE, respectively). The aim of this work was to elucidate whether the involvement of AQPs in the sperm response to cryopreservation relies on the intrinsic freezability of the ejaculate. With this purpose, two different molecules: phloretin (PHL) and 1,3-propanediol (PDO), were used to inhibit sperm AQPs in GFE and PFE. Boar sperm samples were treated with three different concentrations of each inhibitor prior to cryopreservation, and sperm quality and functionality parameters were evaluated in fresh samples and after 30 and 240 min of thawing. Ejaculates were classified as GFE or PFE, according to their post-thaw sperm viability and motility. While the presence of PHL caused a decrease in sperm quality and function compared to the control, samples treated with PDO exhibited better quality and function parameters than the control. In addition, the effects of both inhibitors were more apparent in GFE than in PFE. In conclusion, AQP inhibition has more notable consequences in GFE than in PFE, which can be related to the difference in relative levels of AQPs between these two groups of samples.

91 Invivo- and invitro-produced bovine embryos have different microRNA profiles after invitro individual culture

Invivo- and invitro-produced bovine embryos have different metabolic characteristics, embryonic development, and gene transcription. Additionally, pregnancy rates at 30 days (on average 51% and 34% when using fixed-time AI and invitro production, respectively) are different in beef cattle. Between Days 8 and 17 of the oestrous cycle, concurrent with embryo-maternal recognition, is when 40% of embryonic losses occur. These losses may occur due to altered embryo-maternal cross-talk. MicroRNA (miRNA) can be involved in this communication; however, its potentially regulated pathways in invivo and invitro embryos on Day 9 are unknown. Our hypothesis is that bovine embryos produced invivo and invitro contain different miRNA profiles, even after invivo bovine embryo were invitro cultured. Cows had the follicular wave synchronized and were superovulated to produce invivo or invitro bovine embryos. For the invitro group, on Day −8 of the protocol, the dominant follicles were recovered by ovum pickup, and invitro embryo production was performed to obtain embryos. For the invivo group, on Day −8, the cows were inseminated 12 and 24h after GnRH analogue application and on Day 7 after expected oestrus, uterine flushing was performed to obtain the embryos. Embryos from both groups were individually cultured for 48h. Three pools (of 5 embryos each) per group were used for reverse transcription of miRNAs from total RNA using miScript II RT Kit (Qiagen). Relative levels of 383 bovine miRNAs were determined using the geometric mean of miR-99b, RNU43 snoRNA, and Hm/Ms/Rt U1 snRNA by RT-qPCR. Differences in relative levels of miRNAs were determined by Student's t-test. A total of 210 miRNAs were detected in invivo and invitro embryos, and 13 out of 210 were differently identified between the groups. In invivo embryos, 6 miRNAs were up-regulated, whereas 7 miRNAs were up-regulated in invitro embryos. TARGETSCAN software was used to identify genes predicted as modulated by each miRNA. The top 100 genes predicted were used to identify enriched pathways according to DAVID Bioinformatics Resources. The miRNAs (miR-129, miR-132, miR-155, miR-192, miR-215, and miR-377) up-regulated in invivo embryos modulated pathways that include signaling pathways regulating pluripotency of stem cells (16 genes), TGF-β (11), hippo (10), oestrogen (8), and cell cycle (7). Moreover, miR-23a, miR-338, miR-34a, miR-491, miR-92b, miR-940, and miR-1271, which were increased in invitro embryos, regulate PI3K-Akt (17 genes), signaling pathways regulating pluripotency of stem cells (10), oestrogen (9), toll-like receptor (9), Wnt (9), and HIF-1 (7). The results demonstrate that even after 48h of invitro culture, bovine embryos produced invivo and invitro have different miRNA profiles that modulate pathways associated with embryonic development on Day 9. Furthermore, these results suggest that bioactive molecules, such as miRNAs, can modify embryo-maternal cross-talk, depending on the environment where the embryos are produced. Funding was provided by FAPESP 2017/19681-9, 2014/22887-0, and 2018/13155-6.

Global metabolite profiling based on GC\u2013MS and LC\u2013MS/MS analyses in ABF3-overexpressing soybean with enhanced drought tolerance

Abscisic acid (ABA) is a phytohormone that plays an important role in the adaptive responses to abiotic stresses. We examined the metabolic changes in transgenic soybean that over-expressed Arabidopsis ABA responsive element-binding factor 3 (ABF3), which participates in drought tolerance. Transgenic and non-transgenic plants were exposed to a water deficit, and their metabolic differences were verified by untargeted GC‒MS and LC‒MS/MS analyses. A total of 64 and 476 primary and secondary metabolites from leaf extracts were identified based on GC‒MS and LC‒MS/MS platforms, respectively. Principal component analysis derived from both GC‒MS and LC‒MS/MS data showed a clearly greater separation in the metabolite profiles among three different degrees of drought stress. However, no discrimination of metabolites between transgenic and non-transgenic plants was apparent. Furthermore, except for some free amino acids, quantitative differences in relative levels of those metabolites were less than 50% between genotypes. These results suggest that, during periods of drought, overexpression of ABF3 in transgenic soybean might result in a negligible variance in primary and secondary metabolism when compared with its non-transgenic counterpart.

Metabolite profiles reveal interspecific variation in operation of the Calvin-Benson cycle in both C4 and C3 plants.

Low atmospheric CO2 in recent geological time led to the evolution of carbon-concentrating mechanisms (CCMs) such as C4 photosynthesis in >65 terrestrial plant lineages. We know little about the impact of low CO2 on the Calvin-Benson cycle (CBC) in C3 species that did not evolve CCMs, representing >90% of terrestrial plant species. Metabolite profiling provides a top-down strategy to investigate the operational balance in a pathway. We profiled CBC intermediates in a panel of C4 (Zea mays, Setaria viridis, Flaveria bidentis, and F. trinervia) and C3 species (Oryza sativa, Triticium aestivum, Arabidopsis thaliana, Nicotiana tabacum, and Manihot esculenta). Principal component analysis revealed differences between C4 and C3 species that were driven by many metabolites, including lower ribulose 1,5-bisphosphate in C4 species. Strikingly, there was also considerable variation between C3 species. This was partly due to different chlorophyll and protein contents, but mainly to differences in relative levels of metabolites. Correlation analysis indicated that one contributory factor was the balance between fructose-1,6-bisphosphatase, sedoheptulose-1,7-bisphosphatase, phosphoribulokinase, and Rubisco. Our results point to the CBC having experienced different evolutionary trajectories in C3 species since the ancestors of modern plant lineages diverged. They underline the need to understand CBC operation in a wide range of species.

Effect of Differences in Metabolic Activity of Melanoma Models on Response to Lonidamine plus Doxorubicin

Lonidamine (LND), a metabolic modulator, sensitizes DB-1 human melanoma to doxorubicin (DOX) chemotherapy by acidifying and de-energizing the tumor. This report compares the effects of LND on two human melanoma lines, DB-1 and WM983B, which exhibit different metabolic properties. Using liquid chromatography mass spectrometry and Seahorse analysis, we show that DB-1 was more glycolytic than WM983B in vitro. 31P magnetic resonance spectroscopy (MRS) indicates that LND (100 mg/kg, i.p.) induces similar selective acidification and de-energization of WM983B xenografts in immunosuppressed mice. Over three hours, intracellular pH (pHi) of WM983B decreased from 6.91 ± 0.03 to 6.59 ± 0.10 (p = 0.03), whereas extracellular pH (pHe) of this tumor changed from 7.03 ± 0.05 to 6.89 ± 0.06 (p = 0.19). A decline in bioenergetics (β-NTP/Pi) of 55 ± 5.0% (p = 0.03) accompanied the decline in pHi of WM983B. Using 1H MRS with a selective multiquantum pulse sequence and Hadamard localization, we show that LND induced a significant increase in tumor lactate levels (p < 0.01). LND pre-treatment followed by DOX (10 mg/kg, i.v.) produced a growth delay of 13.7 days in WM983B (p < 0.01 versus control), a growth delay significantly smaller than the 25.4 days that occurred with DB-1 (p = 0.03 versus WM983B). Differences in relative levels of glycolysis may produce differential therapeutic responses of DB-1 and WM983B melanomas.

Sustainability and interactivity between cities and ports: a two-stage data envelopment analysis (DEA) approach

ABSTRACTPorts and cities are intrinsically linked. Port city, which serves as a link between the local and global economy, is an integration of both urban and port systems. Constrained by different regional structures, port cities have developed various formulations over time. Using a two-stage data envelopment analysis (DEA) approach, this paper proposes a new method for measuring the sustainable development of different port city systems. While the previous empirical studies often separate the port system and the urban system, this paper assesses the two systems in an integrated way. Moreover, this paper develops a systematic methodology for measurement of sustainability. Twenty world-leading container port cities are selected for this study using contemporary data. The DEA results display their relative differences in levels of sustainable development, which reveal the effectiveness of the prevailing policies in them. Eventually, recommendations are drawn for other port cities by referring to the best practices.

Health and Inequality in Health in the Nordic Countries

All five Nordic countries emphasise equal and easy access to healthcare. It is the purpose to explore to which extent the populations of these countries have reached good health and high degree of socio-economic equality of health. Each of the five countries has established extensive public health programmes, although with somewhat different emphasis on the causes of ill-health, such as individual behaviour or social circumstances. Attitudes have changed over time, though. We compare these countries to the UK and Germany by using data from the European Social Survey 2002 and 2012 in addition to OECD Statistics from the same years. Health is measured by self-assessed health in five categories, transformed to a cardinal scale using Swedish time trade-off weights. As socio-economic variable we use household income or length of education. Mean health, based on Swedish TTO weights applied to all countries, is above 0.93 in all the Nordic countries and the UK in 2012, while lower in Germany. Rates in good or very good health in the lower income half of the samples are above 0.6 in most countries and even higher in Iceland and Sweden, but below 0.5 in Germany. However, when displayed in a graph the concentration curves nearly follow the diagonal implying almost no income - or education related inequality in self-assessed health weighted by TTO based preferences. The difference is a natural consequence of using different methods. We compared four key life-style related determinants of ill health and found that while there were differences in relative levels between the countries, Germany had a relatively high level of three of these, followed by the UK. We found no association between level of resources used and health status. In general, the Nordic countries have accomplished good health for their populations and high degree of socioeconomic equality in health. Improvements in life-style related determinants of health would be possible, though.

Differences in Relative Levels of 88 microRNAs in Various Regions of the Normal Adult Human Brain.

Since the discovery of microRNAs (miRNAs) in the 1990s, our knowledge about their biology has grown considerably. The increasing number of studies addressing the role of miRNAs in development and in various diseases emphasizes the need for a comprehensive catalogue of accurate sequence, expression and conservation information regarding the large number of miRNAs proposed recently in all organs and tissues. The objective of this study was to provide data on the levels of miRNA expression in 15 tissues of the normal human brain. We conducted an analysis of the relative levels of 88 of the most abundantly expressed and best characterized miRNA derived postmortem from well-characterized samples of various regions of the brains from five normal individuals. The cluster analysis revealed some differences in the relative levels of these miRNAs among the brain regions studied. Such diversity can be explained by different functioning of these brain regions. We hope that the data from the current study are a resource that will be useful to our colleagues in this exciting field, as more hypotheses will be generated and tested with regard to small noncoding RNA in the human brain in healthy and disease states.

Comprehensive Translational Assessment of Human-Induced Pluripotent Stem Cell Derived Cardiomyocytes for Evaluating Drug-Induced Arrhythmias.

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) hold promise for assessment of drug-induced arrhythmias and are being considered for use under the comprehensive in vitro proarrhythmia assay (CiPA). We studied the effects of 26 drugs and 3 drug combinations on 2 commercially available iPSC-CM types using high-throughput voltage-sensitive dye and microelectrode-array assays being studied for the CiPA initiative and compared the results with clinical QT prolongation and torsade de pointes (TdP) risk. Concentration-dependent analysis comparing iPSC-CMs to clinical trial results demonstrated good correlation between drug-induced rate-corrected action potential duration and field potential duration (APDc and FPDc) prolongation and clinical trial QTc prolongation. Of 20 drugs studied that exhibit clinical QTc prolongation, 17 caused APDc prolongation (16 in Cor.4U and 13 in iCell cardiomyocytes) and 16 caused FPDc prolongation (16 in Cor.4U and 10 in iCell cardiomyocytes). Of 14 drugs that cause TdP, arrhythmias occurred with 10 drugs. Lack of arrhythmic beating in iPSC-CMs for the four remaining drugs could be due to differences in relative levels of expression of individual ion channels. iPSC-CMs responded consistently to human ether-a-go-go potassium channel blocking drugs (APD prolongation and arrhythmias) and calcium channel blocking drugs (APD shortening and prevention of arrhythmias), with a more variable response to late sodium current blocking drugs. Current results confirm the potential of iPSC-CMs for proarrhythmia prediction under CiPA, where iPSC-CM results would serve as a check to ion channel and in silico modeling prediction of proarrhythmic risk. A multi-site validation study is warranted.

Control of helminth parasites in juvenile horses

SummaryParasite control in juvenile horses remains a substantial challenge for veterinary practitioners and their clients. This age group is at risk for various types of parasitic disease because their worm burdens tend to be larger and more diverse than in mature horses. This contrast is largely attributable to marked differences in relative levels of acquired immunity. Frequent, perennial anthelmintic treatment is not a sustainable approach for parasite control in this age group, but the simple, surveillance‐based parasite control strategies recommended for mature horses are not appropriate for juveniles either. Maneuvering through the early years of a horse's life requires up‐to‐date knowledge about biology and epidemiology of the parasite species in play as well as local evidence regarding the anthelmintic resistance status of each herd. This article provides an overview of the most important helminth parasites to target in a control programme for juvenile horses, and highlights how the target species change as horses age. Young foals (&lt;2 months) are exposed to Strongyloides westeri and Parascaris spp., whereas the primary target parasite in foals between age 2 months and weaning is Parascaris spp. Beyond weaning, the focus shifts away from ascarids, and the targets instead are strongyles and tapeworms. Gasterophilus spp. and Oxyuris equi are also discussed.

Age- and gender-related changes in pediatric thoracic vertebral morphology

Background contextAlthough it is well known that the growth of thoracic spine changes significantly with age, gender, and vertebral level in the skeletally normal pediatric population, there have been very few studies attempting to comprehensively quantify such variations. Biomechanical and computational models of the growing thoracic spine have provided insight into safety and efficacy of surgical and noninvasive treatments for spinal deformity. However, many of these models only consider growth of the vertebral body and pedicles and assume a consistent growth rate for these structures across thoracic levels. PurposeTo enhance the understanding of age-, gender-, and level-related growth dynamics of the pediatric thoracic spine by comprehensively quantifying the thoracic vertebral morphology for subjects between 1 and 19 years. Study designA retrospective computed tomography (CT) image analysis study. MethodsRetrospectively obtained chest CT scans from 100 skeletally normal pediatric subjects (45 males and 55 females between the ages 1 and 19 years) were digitally reconstructed using medical imaging software. Surface point clouds of thoracic vertebrae were extracted and 26 vertebral geometry parameters were measured using 25 semiautomatically identified surface landmarks and anatomical slices from each thoracic vertebra (T1–T12). Data were assessed for normality, symmetry, and age-, gender-, and level-related differences in geometric measures and growth. Linear regression was performed to estimate of the rates of variation with age for each measurement. ResultsAsymmetries (bilateral, superior-inferior, and anteroposterior) were observed in vertebral body heights, end plate widths and depths, and interfacet widths. Within genders, significant interlevel differences were observed for all geometric measures, and significant differences in the rates of growth were found across thoracic levels for most parameters. Significant differences were observed between genders for pedicle, spinous process, and facet measurements. Growth rates of the pedicles and vertebral bodies were also found to vary significantly between genders. ConclusionsThe rates of growth for most thoracic vertebral structures varied between genders and across vertebral levels. These growth rates followed trends similar to those of their associated vertebral dimensions and this indicates that, across levels and between genders, larger vertebral structures grow at faster rates, whereas smaller structures grow at a slower rate. Such level- and gender-specific information could be used to inform clinical decisions about spinal deformity treatment and adapted for use in biomechanical and computational modeling of thoracic growth and growth modulation.

TcNPR3 from Theobroma cacao functions as a repressor of the pathogen defense response

BackgroundArabidopsis thaliana (Arabidopsis) NON-EXPRESSOR OF PR1 (NPR1) is a transcription coactivator that plays a central role in regulating the transcriptional response to plant pathogens. Developing flowers of homozygous npr3 mutants are dramatically more resistant to infection by the pathogenic bacterium Pseudomonas syringae, suggesting a role of NPR3 as a repressor of NPR1-mediated defense response with a novel role in flower development.ResultsWe report here the characterization of a putative NPR3 gene from the tropical tree species Theobroma cacao (TcNPR3). Like in Arabidopsis, TcNPR3 was constitutively expressed across a wide range of tissue types and developmental stages but with some differences in relative levels compared to Arabidopsis. To test the function of TcNPR3, we performed transgenic complementation analysis by introducing a constitutively expressing putative TcNPR3 transgene into an Arabidopsis npr3 mutant. TcNPR3 expressing Arabidopsis plants were partially restored to the WT pathogen phenotype (immature flowers susceptible to bacterial infection). To test TcNPR3 function directly in cacao tissues, a synthetic microRNA targeting TcNPR3 mRNA was transiently expressed in cacao leaves using an Agrobacterium-infiltration method. TcNPR3 knock down leaf tissues were dramatically more resistance to infection with Phytophthora capsici in a leaf bioassay, showing smaller lesion sizes and reduced pathogen replication.ConclusionsWe conclude that TcNPR3 functions similar to the Arabidopsis NPR3 gene in the regulation of the cacao defense response. Since TcNPR3 did not show a perfect complementation of the Arabidopsis NPR3 mutation, the possibility remains that other functions of TcNPR3 remain to be found. This novel knowledge can contribute to the breeding of resistant cacao varieties against pathogens through molecular markers based approaches or biotechnological strategies.

PP2 - Multinational Consistency of a Discrete Choice Model in Quantifying Health States for the Extended 5-Level EQ-5D

Objectives: To investigate the feasibility of choice experiments for EQ-5D-5L states using computer-based data collection, and to examine the consistency of the estimated parameters values derived after modeling the stated preference data across countries in a multinational study. Methods: Similar choice experiments were executed in Canada, England, The Netherlands, and United States (US). Interactive software was developed to standardize the format of the choice tasks across countries, except for England where face-to-face interviewers were used. The choice task required respondents to choose between two sub-optimal health states. A Bayesian design was used to generate 200 pairs of states that were randomly grouped into 20 blocks. Each respondent completed one block consisting of 10 pairs. A main-effect alternative-specific multinomial probit regression model was used to estimate regression coefficients and to derive values for each health state that capture the relative differences in levels between states. Results: In total there were 1775 respondents, at least 400 respondents from each country, who completed 17750 paired comparisons, resulting into 35500 assessed health states. The mean time to perform one choice task was between 29.2 (US) and 45.2 (England) seconds. All regression coefficients were statistically significant, except level 2 for Usual Activities in The Netherlands (p= 0.51). Three regression coefficients with illogical ordering were observed (The Netherlands: level 3 Pain/ Discomfort, England: Level 3 Usual Activities & Pain/Discomfort). Predictions for the complete set of 3125 EQ-5D-5L states were similar for the four countries. Intra class correlation coefficients between the countries were high: from 0.89 (England vs. US) through 0.99 (Canada vs. US). Conclusions: This proof of concept study indicates that computer-based choice tasks for the EQ-5D-5L in the general population are feasible and parameter of the choice tasks estimates are generally consistent and logical, and the estimated values are largely consistent between the 4 countries.

Peculiarities of the Coherence of Resting-State EEG Activity in Subjects with Different Levels of Aggressiveness

By analyzing the coherence of EEG activity, we examined the spatial organization of the latter in 60 adults of both sexes characterized by dissimilar levels of different aspects of aggressiveness and hostility (diagnosed using the Buss–Durkee and Il’yin questionnaires). Recording of EEG (21 leads positioned according to the 10-20 system) was carried out in the resting state. The greatest numbers of aggressiveness level-related differences in the coherence level (values of the coherence coefficient, Kcoh) were found for oscillations of the β and γ ranges. Despite the high natural interindividual variability, the subgroup of persons with a high level of aggressiveness was characterized, in general, by somewhat smaller values of Kcoh for the δ and θ ranges (in particular in the P4–O2 pair) and greater values of Kcoh for the β1 and β2 rhythms (with an accent in the C3–P3 pair) and γ range (maximum differences in T3–T5). The subgroup of persons with a high level of hostility was distinguished by smaller Kcoh of δ, θ, and γ oscillations and greater Kcoh for the β range in pairs F8–T4 and F7–T3. Aggressive persons demonstrated greater, in general, numbers of low-coherence relations, especially in the δ and θ spectrum segments. The subgroup with domination of autoaggressiveness was characterized by several significantly lower values of Kcoh for the δ and θ ranges.

TASK-3 Channel Deletion in Mice Recapitulates Low-Renin Essential Hypertension

Idiopathic primary hyperaldosteronism (IHA) and low-renin essential hypertension (LREH) are common forms of hypertension, characterized by an elevated aldosterone-renin ratio and hypersensitivity to angiotensin II. They are suggested to be 2 states within a disease spectrum that progresses from LREH to IHA as the control of aldosterone production by the renin-angiotensin system is weakened. The mechanism(s) that drives this progression remains unknown. Deletion of Twik-related acid-sensitive K(+) channels (TASK) subunits, TASK-1 and TASK-3, in mice (T1T3KO) produces a model of human IHA. Here, we determine the effect of deleting only TASK-3 (T3KO) on the control of aldosterone production and blood pressure. We find that T3KO mice recapitulate key characteristics of human LREH, salt-sensitive hypertension, mild overproduction of aldosterone, decreased plasma-renin concentration with elevated aldosterone:renin ratio, hypersensitivity to endogenous and exogenous angiotensin II, and failure to suppress aldosterone production with dietary sodium loading. The relative differences in levels of aldosterone output and aldosterone:renin ratio and in autonomy of aldosterone production between T1T3KO and T3KO mice are reminiscent of differences in human hypertensive patients with LREH and IHA. Our studies establish a model of LREH and suggest that loss of TASK channel activity may be one mechanism that advances the syndrome of low renin hypertension.

Transcriptome asymmetry within mouse zygotes but not between early embryonic sister blastomeres

Transcriptome regionalization is an essential polarity determinant among metazoans, directing embryonic axis formation during normal development. Although conservation of this principle in mammals is assumed, recent evidence is conflicting and it is not known whether transcriptome asymmetries exist within unfertilized mammalian eggs or between the respective cleavage products of early embryonic divisions. We here address this by comparing transcriptome profiles of paired single cells and sub-cellular structures obtained microsurgically from mouse oocytes and totipotent embryos. Paired microsurgical spindle and remnant samples from unfertilized metaphase II oocytes possessed distinguishable profiles. Fertilization produces a totipotent 1-cell embryo (zygote) and associated spindle-enriched second polar body whose paired profiles also differed, reflecting spindle transcript enrichment. However, there was no programmed transcriptome asymmetry between sister cells within 2- or 3-cell embryos. Accordingly, there is transcriptome asymmetry within mouse oocytes, but not between the sister blastomeres of early embryos. This work places constraints on pre-patterning in mammals and provides documentation correlating potency changes and transcriptome partitioning at the single-cell level.

Using Cluster Analysis to Examine the Combinations of Motivation Regulations of Physical Education Students

According to self-determination theory, motivation is multidimensional, with motivation regulations lying along a continuum of self-determination (Ryan & Deci, 2007). Accounting for the different types of motivation in physical activity research presents a challenge. This study used cluster analysis to identify motivation regulation profiles and examined their utility by testing profile differences in relative levels of self-determination (i.e., self-determination index), and theoretical antecedents (i.e., competence, autonomy, relatedness) and consequences (i.e., enjoyment, worry, effort, value, physical activity) of physical education motivation. Students (N= 386) in 6th- through 8th-grade physical education classes completed questionnaires of the variables listed above. Five profiles emerged, including average (n = 81), motivated (n = 82), self-determined (n = 91), low motivation (n = 73), and external (n = 59). Group difference analyses showed that students with greater levels of self-determined forms of motivation, regardless of non-self-determined motivation levels, reported the most adaptive physical education experiences.

Increased nasal epithelial ciliary beat frequency associated with lifestyle tobacco smoke exposure

The ciliated epithelium of the respiratory airways is one of the first vital systemic surfaces in contact with the ambient air. Ex vivo nasal epithelial ciliary beat frequency (CBF) at room temperature is on the order of 7–8 Hz but may be stimulated by irritant exposure. The upregulation of CBF in response to acute irritant exposure is generally considered to be a transient event with eventual return to baseline. However, studies of CBF dynamics in response to typical lifestyle exposures are limited. This study assessed nasal epithelial CBF among human subjects as a function of quantifiable lifestyle tobacco smoke exposure. Nasal epithelial biopsies were obtained from human subjects with well documented histories of tobacco smoke exposure. CBF was determined using a digital photometric technique and concurrent assays of nasal nitric oxide and urine cotinine and creatinine were performed. Mean CBF among active smokers and non-smokers exposed to environmental tobacco smoke (ETS) was elevated over non-smokers. Although there were dramatic differences in relative levels of tobacco smoke exposure, CBF values among tobacco smoke-exposed groups were comparable. Parallel in vitro studies of cultured nasal epithelium exposed to cigarette smoke condensate further supported these observations. These studies suggest that persistent elevation in nasal epithelial CBF is an early, subtle, physiologic effect associated with lifestyle tobacco smoke exposure. The molecular mechanisms that upregulate CBF may also create a cell molecular milieu capable of provoking the eventual emergence of more overt adverse health effects and the pathogenesis of chronic airway disease.