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Swallowing impairment is a major complication of radiation treatment for oropharyngeal cancers. Developing targeted therapies that improve swallowing outcomes relies on an understanding of the mechanisms that influence motor function after radiation treatment. The purpose of this study was to determine whether there is a correlation between radiation induced changes in tongue movement and structural changes in irradiated submental muscles, as well as assess other possible causes for dysfunction. We hypothesized that a clinically relevant total radiation dose to the submental muscles would result in: a) quantifiable changes in tongue strength and displacement during drinking two months post treatment; and b) a profibrotic response and/or fiber type transition in the irradiated tissue. Sprague-Dawley adult male rats received radiation to the submental muscles at total dose-volumes known to provoke dysphagia in humans. A clinical linear accelerator administered 8 fractions of 8Gy for a total of 64Gy. Comparisons were made to sham-treated rats that received anesthesia only. Swallowing function was assessed using videofluoroscopy and tongue strength was analyzed via force lickometer. TGFβ1 expression was analyzed via ELISA. The amount of total collagen was analyzed by picrosirius red staining. Immunofluorescence was used to assess fiber type composition and size. Significant changes in licking function during drinking were observed at two months post treatment, including a slower lick rate and reduced tongue protrusion during licking. In the mylohyoid muscle, significant increases in TGFβ1 protein expression were found post radiation. Significant increases in the percentage of collagen content were observed in the irradiated geniohyoid muscle. No changes in fiber type expression were observed. Results indicate a profibrotic transition within the irradiated swallowing muscles that contributes to tongue dysfunction post-radiation treatment.

Use-wear analysis provides a means of studying traces produced on animal bone during manufacture and use in an effort to reconstruct these processes. Often, these analyses are qualitative and based on experience and expertise. Previous studies have focused on interpreting final traces, but little is known about how these traces develop and change over time. We propose the use of an innovative quantitative method for studying bone surface traces that aims to reduce any unreliable or non-replicable results that can confound more traditional qualitative analyses. We seek to understand the basics of use-wear formation over Time by taking incremental molds of bone specimens subjected to a controlled, mechanical experiment. This study assesses how bone wears during extended use on three Material types (fresh skin, processed leather, or dry bark), from three initial Manufacturing states (unworked, ground with sandstone, or scraped with flint). With data obtained from a confocal disc-scanning microscope, we then apply 3D surface texture analysis using ISO 25178 parameters: surface roughness [Sa], autocorrelation length [Sal], peak curvature [Spc], and upper material ratio [Smr1]. We employ a multilevel multivariate Bayesian model to explain parameter variation under experimental conditions. Our findings show how duration of use strongly affects the transformation of the bone's surface. Unworked bone is completely distinguishable from bone used for long time intervals and those modified by scraping. Interestingly, material wear does not often produce type-specific traces, but does affect the rate of bone alteration and how it is transformed. Specifically, fresh skin transforms bone at a faster rate than other materials. This novel quantitative and experimental approach enhances our understanding of the use of bone as a raw material for making and using tools and provides a foundation for future exploration of archaeological materials and questions.

Archaeological sites in northern Africa provide a rich record of increasing importance for the origins of modern human behaviour and for understanding human dispersal out of Africa. However, the timing and nature of Palaeolithic human behaviour and dispersal across north-western Africa (the Maghreb), and their relationship to local environmental conditions, remain poorly understood. The cave of Rhafas (northeast Morocco) provides valuable chronological information about cultural changes in the Maghreb during the Palaeolithic due to its long stratified archaeological sequence comprising Middle Stone Age (MSA), Later Stone Age (LSA) and Neolithic occupation layers. In this study, we apply optically stimulated luminescence (OSL) dating on sand-sized quartz grains to the cave deposits of Rhafas, as well as to a recently excavated section on the terrace in front of the cave entrance. We hereby provide a revised chronostratigraphy for the archaeological sequence at the site. We combine these results with geological and sedimentological multi-proxy investigations to gain insights into site formation processes and the palaeoenvironmental record of the region. The older sedimentological units at Rhafas were deposited between 135 ka and 57 ka (MIS 6 -MIS 3) and are associated with the MSA technocomplex. Tanged pieces start to occur in the archaeological layers around 109 ka, which is consistent with previously published chronological data from the Maghreb. A well indurated duricrust indicates favourable climatic conditions for the pedogenic cementation by carbonates of sediment layers at the site after 57 ka. Overlying deposits attributed to the LSA technocomplex yield ages of ~21 ka and ~15 ka, corresponding to the last glacial period, and fall well within the previously established occupation phase in the Maghreb. The last occupation phase at Rhafas took place during the Neolithic and is dated to ~7.8 ka.

ObjectiveWe sought to determine the contribution of psychological variables to risk for metabolic syndrome (MetS) among Latinos enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA), and to investigate whether social support moderates these associations, and whether inflammatory markers mediate the association between psychological variables and MetS.Research design and methodsCross-sectional analyses at study baseline were conducted with a national Latino cohort (n = 1,388) that included Mexican Americans, Dominican Americans, Puerto Rican Americans and Central/South Americans. Hierarchical logistic regression analyses were conducted to test the effects of psychosocial variables (chronic stress, depressive symptoms, and social support) on MetS. In addition, separate subgroup-specific models, controlling for nationality, age, gender, socioeconomic position, language spoken at home, exercise, smoking and drinking status, and testing for the effects of chronic stress, depressive symptoms and inflammation (IL-6, CRP, fibrinogen) in predicting risk for MetS were conducted.ResultsIn the overall sample, high chronic stress independently predicted risk for MetS, however this association was found to be significant only in Mexican Americans and Puerto Rican Americans. Social support did not moderate the associations between chronic stress and MetS for any group. Chronic stress was not associated with inflammatory markers in either the overall sample or in each group.ConclusionsOur results suggest a differential contribution of chronic stress to the prevalence of MetS by national groups.

The hormone cortisol is likely to be a key mediator of the stress response that influences multiple physiologic systems that are involved in common chronic disease, including the cardiovascular system, the immune system, and metabolism. In this paper, a candidate gene approach was used to investigate genetic contributions to variability in multiple correlated features of the daily cortisol profile in a sample of European Americans, African Americans, and Hispanic Americans from the Multi-Ethnic Study of Atherosclerosis (MESA). We proposed and applied a new gene-level multiple-phenotype analysis and carried out a meta-analysis to combine the ethnicity specific results. This new analysis, instead of a more routine single marker-single phenotype approach identified a significant association between one gene (ADRB2) and cortisol features (meta-analysis p-value=0.0025), which was not identified by three other commonly used existing analytic strategies: 1. Single marker association tests involving each single cortisol feature separately; 2. Single marker association tests jointly testing for multiple cortisol features; 3. Gene-level association tests separately carried out for each single cortisol feature. The analytic strategies presented consider different hypotheses regarding genotype-phenotype association and imply different costs of multiple testing. The proposed gene-level analysis integrating multiple cortisol features across multiple ethnic groups provides new insights into the gene-cortisol association.

BackgroundShort sleep and poor sleep quality are associated with risk of cardiovascular disease, diabetes, cancer, and mortality. This study examines the contribution of sleep duration and sleep quality on a multisystem biological risk index that is known to be associated with morbidity and mortality.MethodsAnalyses include a population-based sample from the Midlife Development in the United States survey recruited to the Biomarker substudy. A total of 1,023 participants aged 54.5 years (SD = 11.8), 56% female and 77.6% white, were included in the analyses. A multisystem biological risk index was derived from 22 biomarkers capturing cardiovascular, immune, lipid-metabolic, glucose-metabolic, sympathetic, parasympathetic, and hypothalamic-pituitary-adrenal systems. Self-reported average sleep duration was categorized as short (5) sleep.FindingsLinear mixed effect models adjusting for age, gender, race, education, income, BMI, and health status were performed. As compared to normal sleepers, multisystem biological risk in both short (B(SE) = .38(.15), p

C-reactive Protein (CRP) measurements above 10 mg/L have been conventionally treated as acute inflammation and excluded from epidemiologic studies of chronic inflammation. However, recent evidence suggest that such CRP elevations can be seen even with chronic inflammation. The authors assessed 3,300 participants in The Coronary Artery Risk Development in Young Adults study, who had two or more CRP measurements between 1992/3 and 2005/6 to a) investigate characteristics associated with repeated CRP elevation above 10 mg/L; b) identify subgroups at high risk of repeated elevation; and c) investigate the effect of different CRP thresholds on the probability of an elevation being one-time rather than repeated. 225 participants (6.8%) had one-time and 103 (3.1%) had repeated CRP elevation above 10 mg/L. Repeated elevation was associated with obesity, female gender, low income, and sex hormone use. The probability of an elevation above 10 mg/L being one-time rather than repeated was lowest (51%) in women with body mass index above 31 kg/m(2), compared to 82% in others. These findings suggest that CRP elevations above 10 mg/L in obese women are likely to be from chronic rather than acute inflammation, and that CRP thresholds above 10 mg/L may be warranted to distinguish acute from chronic inflammation in obese women.

The forward lunge (FL) may be a promising movement to assess functional outcome after ACL reconstruction. Thus, we aimed to investigate the FL movement pattern before and after ACL reconstruction with a comparison to healthy controls to determine if differences were present. Twenty-eight ACL injured participants and 28 matched healthy controls were included. They performed FL movements while sagittal plane biomechanics of the knee and electromyography (EMG) of nine leg muscles was assessed. The ACL injured group was tested before and 10 months after surgery. The perceived knee function and activity level was assessed by questionnaires. The ACL injured group performed the FL significantly slower than the controls before surgery (mean difference: 0.41 s [95%CI: 0.04-0.79 s; p

BackgroundGene expression may be an important biological mediator in associations between social factors and health. However, previous studies were limited by small sample sizes and use of differing cell types with heterogeneous expression patterns. We use a large population-based cohort with gene expression measured solely in monocytes to investigate associations between seven social factors and expression of genes previously found to be sensitive to social factors.MethodsWe employ three methodological approaches: 1) omnibus test for the entire gene set (Global ANCOVA), 2) assessment of each association individually (linear regression), and 3) machine learning method that performs variable selection with correlated predictors (elastic net).ResultsIn global analyses, significant associations with the a priori defined socially sensitive gene set were detected for major or lifetime discrimination and chronic burden (p = 0.019 and p = 0.047, respectively). Marginally significant associations were detected for loneliness and adult socioeconomic status (p = 0.066, p = 0.093, respectively). No associations were significant in linear regression analyses after accounting for multiple testing. However, a small percentage of gene expressions (up to 11%) were associated with at least one social factor using elastic net.ConclusionThe Global ANCOVA and elastic net findings suggest that a small percentage of genes may be "socially sensitive," (i.e. demonstrate differential expression by social factor), yet single gene approaches such as linear regression may be ill powered to capture this relationship. Future research should further investigate the biological mechanisms through which social factors act to influence gene expression and how systemic changes in gene expression affect overall health.

Use-wear analysis provides a means of studying traces produced on animal bone during manufacture and use in an effort to reconstruct these processes. Often, these analyses are qualitative and based on experience and expertise. Previous studies have focused on interpreting final traces, but little is known about how these traces develop and change over time. We propose the use of an innovative quantitative method for studying bone surface traces that aims to reduce any unreliable or non-replicable results that can confound more traditional qualitative analyses. We seek to understand the basics of use-wear formation over Time by taking incremental molds of bone specimens subjected to a controlled, mechanical experiment. This study assesses how bone wears during extended use on three Material types (fresh skin, processed leather, or dry bark), from three initial Manufacturing states (unworked, ground with sandstone, or scraped with flint). With data obtained from a confocal disc-scanning microscope, we then apply 3D surface texture analysis using ISO 25178 parameters: surface roughness [Sa], autocorrelation length [Sal], peak curvature [Spc], and upper material ratio [Smr1]. We employ a multilevel multivariate Bayesian model to explain parameter variation under experimental conditions. Our findings show how duration of use strongly affects the transformation of the bone's surface. Unworked bone is completely distinguishable from bone used for long time intervals and those modified by scraping. Interestingly, material wear does not often produce type-specific traces, but does affect the rate of bone alteration and how it is transformed. Specifically, fresh skin transforms bone at a faster rate than other materials. This novel quantitative and experimental approach enhances our understanding of the use of bone as a raw material for making and using tools and provides a foundation for future exploration of archaeological materials and questions.

Swallowing impairment is a major complication of radiation treatment for oropharyngeal cancers. Developing targeted therapies that improve swallowing outcomes relies on an understanding of the mechanisms that influence motor function after radiation treatment. The purpose of this study was to determine whether there is a correlation between radiation induced changes in tongue movement and structural changes in irradiated submental muscles, as well as assess other possible causes for dysfunction. We hypothesized that a clinically relevant total radiation dose to the submental muscles would result in: a) quantifiable changes in tongue strength and displacement during drinking two months post treatment; and b) a profibrotic response and/or fiber type transition in the irradiated tissue. Sprague-Dawley adult male rats received radiation to the submental muscles at total dose-volumes known to provoke dysphagia in humans. A clinical linear accelerator administered 8 fractions of 8Gy for a total of 64Gy. Comparisons were made to sham-treated rats that received anesthesia only. Swallowing function was assessed using videofluoroscopy and tongue strength was analyzed via force lickometer. TGFβ1 expression was analyzed via ELISA. The amount of total collagen was analyzed by picrosirius red staining. Immunofluorescence was used to assess fiber type composition and size. Significant changes in licking function during drinking were observed at two months post treatment, including a slower lick rate and reduced tongue protrusion during licking. In the mylohyoid muscle, significant increases in TGFβ1 protein expression were found post radiation. Significant increases in the percentage of collagen content were observed in the irradiated geniohyoid muscle. No changes in fiber type expression were observed. Results indicate a profibrotic transition within the irradiated swallowing muscles that contributes to tongue dysfunction post-radiation treatment. [ABSTRACT FROM AUTHOR]

Archaeological sites in northern Africa provide a rich record of increasing importance for the origins of modern human behaviour and for understanding human dispersal out of Africa. However, the timing and nature of Palaeolithic human behaviour and dispersal across north-western Africa (the Maghreb), and their relationship to local environmental conditions, remain poorly understood. The cave of Rhafas (northeast Morocco) provides valuable chronological information about cultural changes in the Maghreb during the Palaeolithic due to its long stratified archaeological sequence comprising Middle Stone Age (MSA), Later Stone Age (LSA) and Neolithic occupation layers. In this study, we apply optically stimulated luminescence (OSL) dating on sand-sized quartz grains to the cave deposits of Rhafas, as well as to a recently excavated section on the terrace in front of the cave entrance. We hereby provide a revised chronostratigraphy for the archaeological sequence at the site. We combine these results with geological and sedimentological multi-proxy investigations to gain insights into site formation processes and the palaeoenvironmental record of the region. The older sedimentological units at Rhafas were deposited between 135 ka and 57 ka (MIS 6 -MIS 3) and are associated with the MSA technocomplex. Tanged pieces start to occur in the archaeological layers around 109 ka, which is consistent with previously published chronological data from the Maghreb. A well indurated duricrust indicates favourable climatic conditions for the pedogenic cementation by carbonates of sediment layers at the site after 57 ka. Overlying deposits attributed to the LSA technocomplex yield ages of ~21 ka and ~15 ka, corresponding to the last glacial period, and fall well within the previously established occupation phase in the Maghreb. The last occupation phase at Rhafas took place during the Neolithic and is dated to ~7.8 ka.

Short sleep and poor sleep quality are associated with risk of cardiovascular disease, diabetes, cancer, and mortality. This study examines the contribution of sleep duration and sleep quality on a multisystem biological risk index that is known to be associated with morbidity and mortality.Analyses include a population-based sample from the Midlife Development in the United States survey recruited to the Biomarker substudy. A total of 1,023 participants aged 54.5 years (SD = 11.8), 56% female and 77.6% white, were included in the analyses. A multisystem biological risk index was derived from 22 biomarkers capturing cardiovascular, immune, lipid-metabolic, glucose-metabolic, sympathetic, parasympathetic, and hypothalamic-pituitary-adrenal systems. Self-reported average sleep duration was categorized as short (5) sleep.Linear mixed effect models adjusting for age, gender, race, education, income, BMI, and health status were performed. As compared to normal sleepers, multisystem biological risk in both short (B(SE) = .38(.15), p

The hormone cortisol is likely to be a key mediator of the stress response that influences multiple physiologic systems that are involved in common chronic disease, including the cardiovascular system, the immune system, and metabolism. In this paper, a candidate gene approach was used to investigate genetic contributions to variability in multiple correlated features of the daily cortisol profile in a sample of European Americans, African Americans, and Hispanic Americans from the Multi-Ethnic Study of Atherosclerosis (MESA). We proposed and applied a new gene-level multiple-phenotype analysis and carried out a meta-analysis to combine the ethnicity specific results. This new analysis, instead of a more routine single marker-single phenotype approach identified a significant association between one gene (ADRB2) and cortisol features (meta-analysis p-value=0.0025), which was not identified by three other commonly used existing analytic strategies: 1. Single marker association tests involving each single cortisol feature separately; 2. Single marker association tests jointly testing for multiple cortisol features; 3. Gene-level association tests separately carried out for each single cortisol feature. The analytic strategies presented consider different hypotheses regarding genotype-phenotype association and imply different costs of multiple testing. The proposed gene-level analysis integrating multiple cortisol features across multiple ethnic groups provides new insights into the gene-cortisol association.

OBJECTIVE:We sought to determine the contribution of psychological variables to risk for metabolic syndrome (MetS) among Latinos enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA), and to investigate whether social support moderates these associations, and whether inflammatory markers mediate the association between psychological variables and MetS. RESEARCH DESIGN AND METHODS:Cross-sectional analyses at study baseline were conducted with a national Latino cohort (n = 1,388) that included Mexican Americans, Dominican Americans, Puerto Rican Americans and Central/South Americans. Hierarchical logistic regression analyses were conducted to test the effects of psychosocial variables (chronic stress, depressive symptoms, and social support) on MetS. In addition, separate subgroup-specific models, controlling for nationality, age, gender, socioeconomic position, language spoken at home, exercise, smoking and drinking status, and testing for the effects of chronic stress, depressive symptoms and inflammation (IL-6, CRP, fibrinogen) in predicting risk for MetS were conducted. RESULTS:In the overall sample, high chronic stress independently predicted risk for MetS, however this association was found to be significant only in Mexican Americans and Puerto Rican Americans. Social support did not moderate the associations between chronic stress and MetS for any group. Chronic stress was not associated with inflammatory markers in either the overall sample or in each group. CONCLUSIONS:Our results suggest a differential contribution of chronic stress to the prevalence of MetS by national groups.

We aimed to assess the effects of age, sex, body mass index (BMI), and anatomical site on skin thickness in children and adults with diabetes.We studied 103 otherwise healthy children and adolescents with type 1 diabetes aged 5-19 years, and 140 adults with type 1 and type 2 diabetes aged 20-85 years. The thicknesses of both the dermis and subcutis were assessed using ultrasound with a linear array transducer, on abdominal and thigh skin.There was an age-related thickening of both dermis (p

The Asian tiger mosquito, Aedes albopictus, is an anthropophilic aggressive daytime-biting nuisance and an efficient vector of certain arboviruses and filarial nematodes. Over the last 30 years, this species has spread rapidly through human travel and commerce from its native tropical forests of Asia to every continent except Antarctica. In 2011, a population of Asian tiger mosquito (Aedes albopictus) was discovered in Los Angeles (LA) County, California. To determine the probable origin of this invasive species, the genetic structure of the population was compared against 11 populations from the United States and abroad, as well as preserved specimens from a 2001 introduction into California using the mitochondrial cytochrome c oxidase 1 (CO1) gene. A total of 66 haplotypes were detected among samples and were divided into three main groups. Aedes albopictus collected in 2001 and 2011 from LA County were genetically related and similar to those from Asia but distinct from those collected in the eastern and southeastern United States. In view of the high genetic similarities between the 2001 and 2011 LA samples, it is possible that the 2011 population represents in part the descendants of the 2001 introduction. There remains an imperative need for improved surveillance and control strategies for this species.

Marine macroinvertebrates are ideal sentinel organisms to monitor rapid environmental changes associated with climatic phenomena. These organisms build up protective exoskeletons incrementally by biologically-controlled mineralization, which is deeply rooted in long-term evolutionary processes. Recent studies relating potential rapid environmental fluctuations to climate change, such as ocean acidification, suggest modifications on carbonate biominerals of marine invertebrates. However, the influence of known, and recurrent, climatic events on these biological processes during active mineralization is still insufficiently understood. Analysis of Peruvian cockles from the 1982-83 large magnitude El Niño event shows significant alterations of the chemico-structure of carbonate biominerals. Here, we show that bivalves modify the main biomineralization mechanism during the event to continue shell secretion. As a result, magnesium content increases to stabilize amorphous calcium carbonate (ACC), inducing a rise in Mg/Ca unrelated to the associated increase in sea-surface temperature. Analysis of variations in Sr/Ca also suggests that this proxy should not be used in these bivalves to detect the temperature anomaly, while Ba/Ca peaks are recorded in shells in response to an increase in productivity, or dissolved barium in seawater, after the event. Presented data contribute to a better understanding of the effects of abrupt climate change on shell biomineralization, while also offering an alternative view of bivalve elemental proxy reconstructions. Furthermore, biomineralization changes in mollusk shells can be used as a novel potential proxy to provide a more nuanced historical record of El Niño and similar rapid environmental change events.

C-reactive Protein (CRP) measurements above 10 mg/L have been conventionally treated as acute inflammation and excluded from epidemiologic studies of chronic inflammation. However, recent evidence suggest that such CRP elevations can be seen even with chronic inflammation. The authors assessed 3,300 participants in The Coronary Artery Risk Development in Young Adults study, who had two or more CRP measurements between 1992/3 and 2005/6 to a) investigate characteristics associated with repeated CRP elevation above 10 mg/L; b) identify subgroups at high risk of repeated elevation; and c) investigate the effect of different CRP thresholds on the probability of an elevation being one-time rather than repeated. 225 participants (6.8%) had one-time and 103 (3.1%) had repeated CRP elevation above 10 mg/L. Repeated elevation was associated with obesity, female gender, low income, and sex hormone use. The probability of an elevation above 10 mg/L being one-time rather than repeated was lowest (51%) in women with body mass index above 31 kg/m(2), compared to 82% in others. These findings suggest that CRP elevations above 10 mg/L in obese women are likely to be from chronic rather than acute inflammation, and that CRP thresholds above 10 mg/L may be warranted to distinguish acute from chronic inflammation in obese women.

In order to further understand the genetic basis for variation in inherent (untrained) exercise capacity, we examined the brains of 32 male rats selectively bred for high or low running capacity (HCR and LCR, respectively). The aim was to characterize the activation patterns of brain regions potentially involved in differences in inherent running capacity between HCR and LCR. Using quantitative in situ hybridization techniques, we measured messenger ribonuclease (mRNA) levels of c-Fos, a marker of neuronal activation, in the brains of HCR and LCR rats after a single bout of acute treadmill running (7.5-15 minutes, 15° slope, 10 m/min) or after treadmill running to exhaustion (15-51 minutes, 15° slope, initial velocity 10 m/min). During verification of trait differences, HCR rats ran six times farther and three times longer prior to exhaustion than LCR rats. Running to exhaustion significantly increased c-Fos mRNA activation of several brain areas in HCR, but LCR failed to show significant elevations of c-Fos mRNA at exhaustion in the majority of areas examined compared to acutely run controls. Results from these studies suggest that there are differences in central c-Fos mRNA expression, and potential brain activation patterns, between HCR and LCR rats during treadmill running to exhaustion and these differences could be involved in the variation in inherent running capacity between lines.

The basolateral complex of the amygdala (BLA) is a critical component of the neural circuit regulating fear learning. During fear learning and recall, the amygdala and other brain regions, including the hippocampus and prefrontal cortex, exhibit phase-locked oscillations in the high delta/low theta frequency band (∼2-6 Hz) that have been shown to contribute to the learning process. Network oscillations are commonly generated by inhibitory synaptic input that coordinates action potentials in groups of neurons. In the rat BLA, principal neurons spontaneously receive synchronized, inhibitory input in the form of compound, rhythmic, inhibitory postsynaptic potentials (IPSPs), likely originating from burst-firing parvalbumin interneurons. Here we investigated the role of compound IPSPs in the rat and rhesus macaque BLA in regulating action potential synchrony and spike-timing precision. Furthermore, because principal neurons exhibit intrinsic oscillatory properties and resonance between 4 and 5 Hz, in the same frequency band observed during fear, we investigated whether compound IPSPs and intrinsic oscillations interact to promote rhythmic activity in the BLA at this frequency. Using whole-cell patch clamp in brain slices, we demonstrate that compound IPSPs, which occur spontaneously and are synchronized across principal neurons in both the rat and primate BLA, significantly improve spike-timing precision in BLA principal neurons for a window of ∼300 ms following each IPSP. We also show that compound IPSPs coordinate the firing of pairs of BLA principal neurons, and significantly improve spike synchrony for a window of ∼130 ms. Compound IPSPs enhance a 5 Hz calcium-dependent membrane potential oscillation (MPO) in these neurons, likely contributing to the improvement in spike-timing precision and synchronization of spiking. Activation of the cAMP-PKA signaling cascade enhanced the MPO, and inhibition of this cascade blocked the MPO. We discuss these results in the context of spike-timing dependent plasticity and modulation by neurotransmitters important for fear learning, such as dopamine.

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency of premature infants, but its etiology remains unclear. We have previously shown that mucin 2 (Muc2) positive goblet cells are significantly decreased in NEC. We have also shown that ileal bile acids (BAs) are significantly increased during the development of this disease. Because BAs can affect mucins, we hypothesized that elevated ileal BAs contribute to decreased Muc2 in experimental NEC. The role of Muc2 in NEC was evaluated in Winnie +/+ mice, a strain that produces aberrant Muc2. Muc2 and trefoil factor 3 (Tff3) were assessed in neonatal rats subjected to the NEC protocol when bile acids were removed, and in ileal explants from newborn and older rats cultured with and without BAs. Further, the role of active transport of BAs was determined using neonatal rats given the apical sodium dependent bile acid transporter (Asbt) inhibitor SC-435 and in neonatal Asbt knockout mice subjected to the NEC protocol. Mice with aberrant Muc2 had significantly greater incidence and severity of NEC. Using both in vivo and ex vivo techniques, we determined that BAs decrease Muc2 positive cells in neonatal but not older ileum. However, Tff3 positive cells are not decreased by BAs. In addition, active transport of BAs is required for BAs to decrease Muc2 in immature ileum. These data show that functional Muc2 plays a critical role in the prevention of NEC and BAs can potentiate the decreased Muc2 in disease development. Further, BAs have a more profound effect on Muc2 in immature versus older ileum, which may explain at least in part why NEC occurs almost exclusively in premature infants.

The Asian tiger mosquito, Aedes albopictus, is an anthropophilic aggressive daytime-biting nuisance and an efficient vector of certain arboviruses and filarial nematodes. Over the last 30 years, this species has spread rapidly through human travel and commerce from its native tropical forests of Asia to every continent except Antarctica. In 2011, a population of Asian tiger mosquito (Aedes albopictus) was discovered in Los Angeles (LA) County, California. To determine the probable origin of this invasive species, the genetic structure of the population was compared against 11 populations from the United States and abroad, as well as preserved specimens from a 2001 introduction into California using the mitochondrial cytochrome c oxidase 1 (CO1) gene. A total of 66 haplotypes were detected among samples and were divided into three main groups. Aedes albopictus collected in 2001 and 2011 from LA County were genetically related and similar to those from Asia but distinct from those collected in the eastern and southeastern United States. In view of the high genetic similarities between the 2001 and 2011 LA samples, it is possible that the 2011 population represents in part the descendants of the 2001 introduction. There remains an imperative need for improved surveillance and control strategies for this species. [ABSTRACT FROM AUTHOR]