Imbalanced Hemolymph Lipid Levels Affect Feeding Motivation in the Two-Spotted Cricket, Gryllus bimaculatus.

PubMed

Konuma, Takahiro; Tsukamoto, Yusuke; Nagasawa, Hiromichi; Nagata, Shinji

2016-01-01

Insect feeding behavior is regulated by many intrinsic factors, including hemolymph nutrient levels. Adipokinetic hormone (AKH) is a peptide factor that modulates hemolymph nutrient levels and regulates the nutritional state of insects by triggering the transfer of lipids into the hemolymph. We recently demonstrated that RNA interference (RNAi)-mediated knockdown of the AKH receptor (AKHR) reduces hemolymph lipid levels, causing an increase in the feeding frequency of the two-spotted cricket, Gryllus bimaculatus. This result indicated that reduced hemolymph lipid levels might motivate crickets to feed. In the present study, to elucidate whether hemolymph lipid levels contribute to insect feeding behavior, we attempted to manipulate hemolymph lipid levels via the lipophorin (Lp)-mediated lipid transferring system in G. bimaculatus. Of the constituent proteins in Lp, we focused on apolipophorin-III (GrybiApoLp-III) because of its possible role in facilitating lipid mobilization. First, we used RNAi to reduce the expression of GrybiApoLp-III. RNAi-mediated knockdown of GrybiApoLp-III had little effect on basal hemolymph lipid levels and the amount of food intake. In addition, hemolymph lipid levels remained static even after injecting AKH into GrybiApoLp-IIIRNAi crickets. These observations indicated that ApoLp-III does not maintain basal hemolymph lipid levels in crickets fed ad libitum, but is necessary for mobilizing lipid transfer into the hemolymph following AKH stimulation. Second, Lp (containing lipids) was injected into the hemolymph to induce a temporary increase in hemolymph lipid levels. Consequently, the initiation of feeding was delayed in a dose-dependent manner, indicating that increased hemolymph lipid levels reduced the motivation to feed. Taken together, these data validate the importance of basal hemolymph lipid levels in the control of energy homeostasis and for regulating feeding behavior in crickets.

Imbalanced Hemolymph Lipid Levels Affect Feeding Motivation in the Two-Spotted Cricket, Gryllus bimaculatus

PubMed Central

Konuma, Takahiro; Tsukamoto, Yusuke; Nagasawa, Hiromichi; Nagata, Shinji

2016-01-01

Insect feeding behavior is regulated by many intrinsic factors, including hemolymph nutrient levels. Adipokinetic hormone (AKH) is a peptide factor that modulates hemolymph nutrient levels and regulates the nutritional state of insects by triggering the transfer of lipids into the hemolymph. We recently demonstrated that RNA interference (RNAi)-mediated knockdown of the AKH receptor (AKHR) reduces hemolymph lipid levels, causing an increase in the feeding frequency of the two-spotted cricket, Gryllus bimaculatus. This result indicated that reduced hemolymph lipid levels might motivate crickets to feed. In the present study, to elucidate whether hemolymph lipid levels contribute to insect feeding behavior, we attempted to manipulate hemolymph lipid levels via the lipophorin (Lp)-mediated lipid transferring system in G. bimaculatus. Of the constituent proteins in Lp, we focused on apolipophorin-III (GrybiApoLp-III) because of its possible role in facilitating lipid mobilization. First, we used RNAi to reduce the expression of GrybiApoLp-III. RNAi-mediated knockdown of GrybiApoLp-III had little effect on basal hemolymph lipid levels and the amount of food intake. In addition, hemolymph lipid levels remained static even after injecting AKH into GrybiApoLp-IIIRNAi crickets. These observations indicated that ApoLp-III does not maintain basal hemolymph lipid levels in crickets fed ad libitum, but is necessary for mobilizing lipid transfer into the hemolymph following AKH stimulation. Second, Lp (containing lipids) was injected into the hemolymph to induce a temporary increase in hemolymph lipid levels. Consequently, the initiation of feeding was delayed in a dose-dependent manner, indicating that increased hemolymph lipid levels reduced the motivation to feed. Taken together, these data validate the importance of basal hemolymph lipid levels in the control of energy homeostasis and for regulating feeding behavior in crickets. PMID:27144650

Decreased ghrelin and des-acyl ghrelin plasma levels in patients affected by pharmacoresistant epilepsy and maintained on the ketogenic diet.

PubMed

Marchiò, Maddalena; Roli, Laura; Giordano, Carmela; Trenti, Tommaso; Guerra, Azzurra; Biagini, Giuseppe

2018-03-23

The gastric hormones ghrelin and des-acyl ghrelin have been found to be altered in patients treated with antiepileptic drugs. However, it is unknown if these hormones could be modified by other antiepileptic treatments, such as the ketogenic diet. Especially, a reduction in ghrelin levels could be relevant in view of the growth retardation observed under ketogenic diet treatment. For this reason we aimed to determine the changes in ghrelin and des-acyl ghrelin plasma levels in children affected by refractory epilepsy and treated with the ketogenic diet up to 90 days. Both peptides were measured by immunoassays in plasma obtained from 16 children. Ghrelin plasma levels were progressively reduced by the ketogenic diet, reaching a minimum corresponding to 42% of basal levels after 90 days of ketogenic diet (P < 0.05, Duncan's test). Des-acyl ghrelin plasma levels were similarly affected, reaching minimal levels at 30 days (65% of basal levels), and maintaining a significant reduction until 90 days after the onset of ketogenic diet (P < 0.01 for both time intervals). No significant changes in growth were observed during the monitored period of ketogenic diet administration. Ghrelin and des-acyl ghrelin are downregulated by the ketogenic diet in children affected by refractory epilepsy. Although no significant changes in growth were observed during the short time period of our investigation, the reduction in ghrelin availability may explain the reported growth retardation found in children treated with the ketogenic diet in the long-term. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Erythropoietin during hypoglycaemia in type 1 diabetes: relation to basal renin-angiotensin system activity and cognitive function.

PubMed

Kristensen, Peter Lommer; Høi-Hansen, Thomas; Olsen, Niels Vidiendal; Pedersen-Bjergaard, Ulrik; Thorsteinsson, Birger

2009-07-01

Preservation of cognitive function during hypoglycaemic episodes is crucial for patients with insulin-treated diabetes to avoid severe hypoglycaemic events. Erythropoietin has neuroprotective potential. However, the role of erythropoietin during hypoglycaemia is unclear. The aim of the study was to explore plasma erythropoietin response to hypoglycaemia and the relationship to basal renin-angiotensin system (RAS) activity and cognitive function. We performed a single-blinded, controlled, cross-over study with induced hypoglycaemia or maintained glycaemic level. Nine patients with type 1 diabetes with high and nine with low activity in RAS were studied. Hypoglycaemia was induced using a standardized insulin-infusion. Overall, erythropoietin concentrations increased during hypoglycaemia. In the high RAS group erythropoietin rose 29% (p=0.032) whereas no significant response was observed in the low RAS group (7% increment; p=0.43). Independently, both hypoglycaemia and high RAS activity were associated with higher levels of erythropoietin (p=0.02 and 0.04, respectively). Low plasma erythropoietin at baseline was associated with poorer cognitive performance during hypoglycaemia. Hypoglycaemia triggers a rise in plasma erythropoietin in patients with type 1 diabetes. The response is influenced by basal RAS activity. Erythropoietin may carry a neuroprotective potential during hypoglycaemia.

Retinoic acid stimulates interstitial collagenase messenger ribonucleic acid in osteosarcoma cells

NASA Technical Reports Server (NTRS)

Connolly, T. J.; Clohisy, J. C.; Shilt, J. S.; Bergman, K. D.; Partridge, N. C.; Quinn, C. O.

1994-01-01

The rat osteoblastic osteosarcoma cell line UMR 106-01 secretes interstitial collagenase in response to retinoic acid (RA). The present study demonstrates by Northern blot analysis that RA causes an increase in collagenase messenger RNA (mRNA) at 6 h, which is maximal at 24 h (20.5 times basal) and declines toward basal level by 72 h. This stimulation is dose dependent, with a maximal response at 5 x 10(-7) M RA. Nuclear run-on assays show a greater than 20-fold increase in the rate of collagenase mRNA transcription between 12-24 h after RA treatment. Cycloheximide blocks RA stimulation of collagenase mRNA, demonstrating the need for de novo protein synthesis. RA not only causes an increase in collagenase secretion, but is known to decrease collagen synthesis in UMR 106-01 cells. In this study, the increase in collagenase mRNA is accompanied by a concomitant decrease in the level of alpha 1(I) procollagen mRNA, which is maximal at 24 h (70% decrease), with a return to near-control levels by 72 h. Nuclear run-on assays demonstrated that the decrease in alpha 1 (I) procollagen expression does not have a statistically significant transcriptional component. RA did not statistically decrease the stability of alpha 1 (I) procollagen mRNA (calculated t1/2 = 8.06 +/- 0.30 and 9.01 +/- 0.62 h in the presence and absence of RA, respectively). However, transcription and stability together probably contribute to the major decrease in stable alpha 1 (I) procollagen mRNA observed. Cycloheximide treatment inhibits basal level alpha 1 (I) procollagen mRNA accumulation, demonstrating the need for on-going protein synthesis to maintain basal expression of this gene.

Differential expression of oil palm pathology genes during interactions with Ganoderma boninense and Trichoderma harzianum.

PubMed

Alizadeh, Fahimeh; Abdullah, Siti Nor Akmar; Khodavandi, Alireza; Abdullah, Faridah; Yusuf, Umi Kalsom; Chong, Pei Pei

2011-07-01

The expression profiles of Δ9 stearoyl-acyl carrier protein desaturase (SAD1 and SAD2) and type 3 metallothionein (MT3-A and MT3-B) were investigated in seedlings of oil palm (Elaeis guineensis) artificially inoculated with the pathogenic fungus Ganoderma boninense and the symbiotic fungus Trichoderma harzianum. Expression of SAD1 and MT3-A in roots and SAD2 in leaves were significantly up-regulated in G. boninense inoculated seedlings at 21 d after treatment when physical symptoms had not yet appeared and thereafter decreased to basal levels when symptoms became visible. Our finding demonstrated that the SAD1 expression in leaves was significantly down-regulated to negligible levels at 42 and 63 d after treatment. The transcripts of MT3 genes were synthesized in G. boninense inoculated leaves at 42 d after treatment, and the analyses did not show detectable expression of these genes before 42 d after treatment. In T. harzianum inoculated seedlings, the expression levels of SAD1 and SAD2 increased gradually and were stronger in roots than leaves, while for MT3-A and MT3-B, the expression levels were induced in leaves at 3d after treatment and subsequently maintained at same levels until 63d after treatment. The MT3-A expression was significantly up-regulated in roots at 3d after treatment and thereafter were maintained at this level. Both SAD and MT3 expression were maintained at maximum levels or at levels higher than basal. This study demonstrates that oil palm was able to distinguish between pathogenic and symbiotic fungal interactions, thus resulting in different transcriptional activation profiles of SAD and MT3 genes. Increases in expression levels of SAD and MT3 would lead to enhanced resistance against G. boninense and down-regulation of genes confer potential for invasive growth of the pathogen. Differences in expression profiles of SAD and MT3 relate to plant resistance mechanisms while supporting growth enhancing effects of symbiotic T. harzianum. Copyright © 2011 Elsevier GmbH. All rights reserved.

Homeostatic maintenance of ponderosa pine gas exchange in response to stand density changes.

PubMed

McDowell, Nate G; Adams, Henry D; Bailey, John D; Hess, Marcey; Kolb, Thomas E

2006-06-01

Homeostatic maintenance of gas exchange optimizes carbon gain per water loss. Homeostasis is regulated by short-term physiological and long-term structural mechanisms, both of which may respond to changes in resource availability associated with competition. Therefore, stand density regulation via silvicultural manipulations may facilitate growth and survival through mechanisms operating at both short and long timescales. We investigated the responses of ponderosa pine (Pinus ponderosa) to stand basal area manipulations in Arizona, USA. Stand basal area was manipulated to seven replicated levels in 1962 and was maintained for four decades by decadal thinning. We measured basal area increment (BAI) to assess the response and sustainability of wood growth, carbon isotope discrimination (A) inferred from annual rings to assess the response of crown gas exchange, and ratios of leaf area to sapwood area (A(l):A(s)) to assess longer term structural acclimation. Basal area treatments increased soil water potential (r2 = 0.99) but did not affect photosynthetic capacity. BAI increased within two years of thinning, and the 40-year mean BAI was negatively correlated with stand basal area (r2 = 0.98). delta was negatively correlated with stand basal area for years 5 through 12 after thinning (r2 = 0.90). However, delta was relatively invariant with basal area for the period 13-40 years after initial thinning despite maintenance of treatment basal areas via repeated decadal thinnings. Independent gas exchange measurements verified that the ratio of photosynthesis to stomatal conductance was invariant with basal area, but absolute values of both were elevated at lower basal areas. A(l):A(s) was negatively correlated with basal area (r2 = 0.93). We hypothesize that increased A(l):A(s) is a homeostatic response to increased water availability that maximizes water-use efficiency and whole-tree carbon uptake. Elevated A(l):A(s) of trees at low basal areas was associated with greater resilience to climate, i.e., greater absolute BAI during drought; however, trees with high A(l):A(s) in low basal area stands also exhibited the greatest sensitivity to drought, i.e., greater relative decline in BAI.

Basal p53 expression is indispensable for mesenchymal stem cell integrity.

PubMed

Boregowda, Siddaraju V; Krishnappa, Veena; Strivelli, Jacqueline; Haga, Christopher L; Booker, Cori N; Phinney, Donald G

2018-03-01

Marrow-resident mesenchymal stem cells (MSCs) serve as a functional component of the perivascular niche that regulates hematopoiesis. They also represent the main source of bone formed in adult bone marrow, and their bifurcation to osteoblast and adipocyte lineages plays a key role in skeletal homeostasis and aging. Although the tumor suppressor p53 also functions in bone organogenesis, homeostasis, and neoplasia, its role in MSCs remains poorly described. Herein, we examined the normal physiological role of p53 in primary MSCs cultured under physiologic oxygen levels. Using knockout mice and gene silencing we show that p53 inactivation downregulates expression of TWIST2, which normally restrains cellular differentiation to maintain wild-type MSCs in a multipotent state, depletes mitochondrial reactive oxygen species (ROS) levels, and suppresses ROS generation and PPARG gene and protein induction in response to adipogenic stimuli. Mechanistically, this loss of adipogenic potential skews MSCs toward an osteogenic fate, which is further potentiated by TWIST2 downregulation, resulting in highly augmented osteogenic differentiation. We also show that p53 - /- MSCs are defective in supporting hematopoiesis as measured in standard colony assays because of decreased secretion of various cytokines including CXCL12 and CSF1. Lastly, we show that transient exposure of wild-type MSCs to 21% oxygen upregulates p53 protein expression, resulting in increased mitochondrial ROS production and enhanced adipogenic differentiation at the expense of osteogenesis, and that treatment of cells with FGF2 mitigates these effects by inducing TWIST2. Together, these findings indicate that basal p53 levels are necessary to maintain MSC bi-potency, and oxygen-induced increases in p53 expression modulate cell fate and survival decisions. Because of the critical function of basal p53 in MSCs, our findings question the use of p53 null cell lines as MSC surrogates, and also implicate dysfunctional MSC responses in the pathophysiology of p53-related skeletal disorders.

Seasonal thermoregulatory responses in mammals.

PubMed

Lovegrove, Barry G

2005-05-01

This study examined the proportional seasonal winter adjustments of total and mass-specific basal power (watts and watts g-1, respectively), thermal conductance (watts g-1 degrees C-1), non-shivering thermogenesis capacity (ratio of NST/basal power), body temperature ( degrees C), and body mass (g) of mammals. The responses are best summarized for three different body size classes; small mammals (<100 g), intermediate-sized mammals (0.1-10 kg), and large mammals (>10 kg). The principal adjustments of the small mammals center on energy conservation, especially the Dehnel Effect, the winter reduction in body size of as much as 50%, accompanied by reductions in mass-specific basal power. On average, these reductions reduce the total basal power approximately in direct proportion to the mass reductions. Reductions in mass-specific basal power are matched by concomitant reductions in conductance to maintain the setpoint body temperature during winter. The overall thermoregulatory adjustments in small mammals serve to (a) lower overall winter power consumption, (b) maintain the setpoint body temperature, and (c) lower the lower critical limit of thermoneutrality and hence thermoregulatory costs. In intermediate-size mammals, the seasonal response is centered more on increasing thermogenic capacity by increasing basal power and NST capacity, accompanied by predictable and large reductions in conductance. The Dehnel effect is negligible. Very large mammals undergo the largest reductions in total and mass-specific basal power and conductance. However, there are too few data to resolve whether the reductions in total basal power can be attributed to the Dehnel effect, because the moderate decreases in body mass may also be caused by nutritional stress. Apart from the seasonal changes in basal power, these observations are consistent with the predictions of Heldmaier's seasonal acclimatization model.

Endocrine basis of the reproductive pattern of the Gentoo penguin (Pygoscelis papua): winter breeding and extended laying period in northern populations.

PubMed

Mauget, R; Garcia, V; Jouventin, P

1995-05-01

Changes in plasma LH, prolactin, testosterone, estradiol, and progesterone were investigated throughout moult and reproduction in free-living male and female Gentoo penguins (Pygoscelis papua) at Crozet Island (46 degrees S, 51 degrees E), where this species is able to relay after a reproductive failure. In both sexes, LH, prolactin, and steroid hormones, remained at basal levels during the moult. LH level was highest at the time of arrival at the colony for breeding and, although it decreased after courtship, it did not drop at basal value by incubation and first chick brooding period. Prolactin peaked for both chick brooding periods; replacement clutch was associated with an increased secretion of LH, whereas high prolactin levels were maintained. Testosterone, in male, and estradiol, in female, peaked during courtship I and chick brooding II; progesterone, in female, peaked during courtship I and II. These hormonal patterns are consistent with those observed in passerine species which are also able to relay after a reproductive failure. Winter breeding observed at Crozet Island might reflect the extreme adaptive capacity of Gentoo penguin species.

Control of arousal by the orexin neurons

PubMed Central

Alexandre, Chloe; Andermann, Mark L; Scammell, Thomas E

2013-01-01

The orexin-producing neurons in the lateral hypothalamus play an essential role in promoting arousal and maintaining wakefulness. These neurons receive a broad variety of signals related to environmental, physiological and emotional stimuli; they project to almost every brain region involved in the regulation of wakefulness; and they fire most strongly during active wakefulness, high motor activation, and sustained attention. This review focuses on the specific neuronal pathways through which the orexin neurons promote wakefulness and maintain high level of arousal, and how recent studies using optogenetic and pharmacogenetic methods have demonstrated that the locus coeruleus, the tuberomammillary nucleus, and the basal forebrain are some of the key sites mediating the arousing actions of orexins. PMID:23683477

Long-Term Citalopram Treatment Alters the Stress Responses of the Cortical Dopamine and Noradrenaline Systems: the Role of Cortical 5-HT1A Receptors

PubMed Central

Kaneko, Fumi; Kishikawa, Yuki; Hanada, Yuuki; Yamada, Makiko; Kakuma, Tatsuyuki; Kawahara, Hiroshi; Nishi, Akinori

2016-01-01

Background: Cortical dopamine and noradrenaline are involved in the stress response. Citalopram, a selective serotonin reuptake inhibitor, has direct and indirect effects on the serotonergic system. Furthermore, long-term treatment with citalopram affects the dopamine and noradrenaline systems, which could contribute to the therapeutic action of antidepressants. Methods: The effects of long-term treatment with citalopram on the responses of the dopamine and noradrenaline systems in the rat prefrontal cortex to acute handling stress were evaluated using in vivo microdialysis. Results: Acute handling stress increased dopamine and noradrenaline levels in the prefrontal cortex. The dopamine and noradrenaline responses were suppressed by local infusion of a 5-HT1A receptor agonist, 7-(Dipropylamino)-5,6,7,8-tetrahydronaphthalen-1-ol;hydrobromide, into the prefrontal cortex. The dopamine response was abolished by long-term treatment with citalopram, and the abolished dopamine response was reversed by local infusion of a 5-HT1A receptor antagonist, (Z)-but-2-enedioic acid;N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-ylcyclohexanecarboxamide into the prefrontal cortex. On the other hand, long-term treatment with citalopram reduced the basal noradrenaline levels (approximately 40% of the controls), but not the basal dopamine levels. The noradrenaline response was maintained despite the low basal noradrenaline levels. Signaling from the 5-HT1A receptors and α2-adrenoceptors was not involved in the decrease in the basal noradrenaline levels but partially affected the noradrenaline response. Conclusions: Chronic citalopram treatment differentially suppresses the dopamine and noradrenaline systems in the prefrontal cortex, and the dopamine stress response was preferentially controlled by upregulating 5-HT1A receptor signaling. Our findings provide insight into how antidepressants modulate the dopamine and noradrenaline systems to overcome acute stress. PMID:27029212

DOR undergoes nucleo-cytoplasmic shuttling, which involves passage through the nucleolus.

PubMed

Mauvezin, Caroline; Sancho, Ana; Ivanova, Saska; Palacin, Manuel; Zorzano, Antonio

2012-09-21

DOR is a bi-functional protein that regulates transcription and enhances starvation-induced autophagy. While autophagy has been mostly described as a stress-response mechanism, cells also need autophagy to maintain homeostasis in basal conditions. However, the mechanisms regulating basal autophagy still remain unknown. Our results show that DOR acts in basal autophagy. Indeed, DOR already undergoes nucleo-cytoplasmic shuttling in basal conditions and, surprisingly, DOR exits continuously the nucleus and traverses the nucleolus. However, the nucleolus integrity is not essential for both DOR nucleo-cytoplasmic shuttling and DOR function on basal autophagy. Taken together, we propose that DOR exit from the nucleus is essential for basal autophagy stimulation even under nucleolus disruption. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Neural nitric oxide gene inactivation affects the release profile of oxytocin into the blood in response to forced swimming.

PubMed

Orlando, G F; Langnaese, K; Landgraf, R; Spina, M G; Wolf, G; Engelmann, M

2007-02-01

This study was undertaken to examine the importance of nitric oxide (NO) generated by the neural isoform of the nitric oxide synthase (nNOS) on the activity of the hypothalamic neurohypophyseal system in neural nitric oxide synthase knock-out (KO) and wild-type (WT) mice under basal conditions and in response to forced swimming. The intensity of the hybridisation signal for vasopressin (AVP) in the hypothalamic supraoptic nucleus (SON) was significantly higher in KO mice when compared with WT, whereas oxytocin (OXT) basal mRNA levels were similar in both groups. Although the basal peripheral release of AVP and OXT was equivalent in both genotypes, we observed in KO mice a significant drop of AVP and OXT plasma values 15 min after stressor onset and a robust increase in the OXT plasma concentration at 60 min. These findings suggest that in the male mouse, NO inhibits AVP gene transcription in magnocellular neurones of the SON and collaborates in maintaining constant AVP and OXT plasma levels following acute stressor exposure, exerting a bimodal regulatory action on OXT secretion. We conclude that NO is involved in the regulation of magnocellular neurones of the SON, and it is preferentially implicated in the attenuation of the peripheral release of OXT induced by acute stressor exposure.

Basal Immunoglobulin Signaling Actively Maintains Developmental Stage in Immature B Cells

PubMed Central

Tze, Lina E; Schram, Brian R; Lam, Kong-Peng; Hogquist, Kristin A; Hippen, Keli L; Liu, Jiabin; Shinton, Susan A; Otipoby, Kevin L; Rodine, Peter R; Vegoe, Amanda L; Kraus, Manfred; Hardy, Richard R; Schlissel, Mark S; Rajewsky, Klaus

2005-01-01

In developing B lymphocytes, a successful V(D)J heavy chain (HC) immunoglobulin (Ig) rearrangement establishes HC allelic exclusion and signals pro-B cells to advance in development to the pre-B stage. A subsequent functional light chain (LC) rearrangement then results in the surface expression of IgM at the immature B cell stage. Here we show that interruption of basal IgM signaling in immature B cells, either by the inducible deletion of surface Ig via Cre-mediated excision or by incubating cells with the tyrosine kinase inhibitor herbimycin A or the phosphatidylinositol 3-kinase inhibitor wortmannin, led to a striking “back-differentiation” of cells to an earlier stage in B cell development, characterized by the expression of pro-B cell genes. Cells undergoing this reversal in development also showed evidence of new LC gene rearrangements, suggesting an important role for basal Ig signaling in the maintenance of LC allelic exclusion. These studies identify a previously unappreciated level of plasticity in the B cell developmental program, and have important implications for our understanding of central tolerance mechanisms. PMID:15752064

BAG3 regulates total MAP1LC3B protein levels through a translational but not transcriptional mechanism.

PubMed

Rodríguez, Andrea E; López-Crisosto, Camila; Peña-Oyarzún, Daniel; Salas, Daniela; Parra, Valentina; Quiroga, Clara; Morawe, Tobias; Chiong, Mario; Behl, Christian; Lavandero, Sergio

2016-01-01

Autophagy is mainly regulated by post-translational and lipid modifications of ATG proteins. In some scenarios, the induction of autophagy is accompanied by increased levels of certain ATG mRNAs such as MAP1LC3B/LC3B, ATG5 or ATG12. However, little is known about the regulation of ATG protein synthesis at the translational level. The cochaperone of the HSP70 system BAG3 (BCL2-associated athanogene 3) has been associated to LC3B lipidation through an unknown mechanism. In the present work, we studied how BAG3 controls autophagy in HeLa and HEK293 cells. Our results showed that BAG3 regulates the basal amount of total cellular LC3B protein by controlling its mRNA translation. This effect was apparently specific to LC3B because other ATG protein levels were not affected. BAG3 knockdown did not affect LC3B lipidation induced by nutrient deprivation or proteasome inhibition. We concluded that BAG3 maintains the basal amount of LC3B protein by controlling the translation of its mRNA in HeLa and HEK293 cells.

BAG3 regulates total MAP1LC3B protein levels through a translational but not transcriptional mechanism

PubMed Central

Rodríguez, Andrea E.; López-Crisosto, Camila; Peña-Oyarzún, Daniel; Salas, Daniela; Parra, Valentina; Quiroga, Clara; Morawe, Tobias; Chiong, Mario; Behl, Christian; Lavandero, Sergio

2016-01-01

ABSTRACT Autophagy is mainly regulated by post-translational and lipid modifications of ATG proteins. In some scenarios, the induction of autophagy is accompanied by increased levels of certain ATG mRNAs such as MAP1LC3B/LC3B, ATG5 or ATG12. However, little is known about the regulation of ATG protein synthesis at the translational level. The cochaperone of the HSP70 system BAG3 (BCL2-associated athanogene 3) has been associated to LC3B lipidation through an unknown mechanism. In the present work, we studied how BAG3 controls autophagy in HeLa and HEK293 cells. Our results showed that BAG3 regulates the basal amount of total cellular LC3B protein by controlling its mRNA translation. This effect was apparently specific to LC3B because other ATG protein levels were not affected. BAG3 knockdown did not affect LC3B lipidation induced by nutrient deprivation or proteasome inhibition. We concluded that BAG3 maintains the basal amount of LC3B protein by controlling the translation of its mRNA in HeLa and HEK293 cells. PMID:26654586

Texture evolution during thermomechanical processing in rare earth free magnesium alloys

NASA Astrophysics Data System (ADS)

Miller, Victoria Mayne

The use of wrought magnesium alloys is highly desirable for a wide range of applications where low component weight is desirable due to the high specific strength and stiffness the alloys can achieve. However, the implementation of wrought magnesium has been hindered by the limited room temperature formability which typically results from deformation processing. This work identifies opportunities for texture modification during thermomechanical processing of conventional (rare earth free) magnesium alloys via a combination of experimental investigation and polycrystal plasticity simulations. During deformation, it is observed that a homogeneous distribution of coarse intermetallic particles efficiently weakens deformation texture at all strain levels, while a highly inhomogeneous particle distribution is only effective at high strains. The particle deformation effects are complemented by the addition of alkaline earth solute, which modifies the relative deformation mode activity. During recrystallization, grains with basal orientations recrystallize more readily than off-basal grains, despite similar levels of internal misorientation. Dislocation substructure investigations revealed that this is a result of enhanced nucleation in the basal grains due to the dominance of prismatic slip. This dissertation identifies avenues to enhance the potential formability of magnesium alloys during thermomechanical processing by minimizing the evolved texture strength. The following are the identified key aspects of microstructural control: -Maintaining a fine grain size, likely via Zener pinning, to favorably modify deformation mode activity and homogenize deformation. -Developing a coarse, homogeneously distributed population of coarse intermetallic particles to promote a diffuse deformation texture. -Minimizing the activity of prismatic slip to retard the recrystallization of grains with basal orientations, allowing the development of a more diffuse recrystallization texture.

The ZntA-like NpunR4017 plays a key role in maintaining homeostatic levels of zinc in Nostoc punctiforme.

PubMed

Hudek, L; Bräu, L; Michalczyk, A A; Neilan, B A; Meeks, J C; Ackland, M L

2015-12-01

Analysis of cellular response to zinc exposure provides insights into how organisms maintain homeostatic levels of zinc that are essential, while avoiding potentially toxic cytosolic levels. Using the cyanobacterium Nostoc punctiforme as a model, qRT-PCR analyses established a profile of the changes in relative mRNA levels of the ZntA-like zinc efflux transporter NpunR4017 in response to extracellular zinc. In cells treated with 18 μM of zinc for 1 h, NpunR4017 mRNA levels increased by up to 1300 % above basal levels. The accumulation and retention of radiolabelled (65)Zn by NpunR4107-deficient and overexpressing strains were compared to wild-type levels. Disruption of NpunR4017 resulted in a significant increase in zinc accumulation up to 24 % greater than the wild type, while cells overexpressing NpunR4107 accumulated 22 % less than the wild type. Accumulation of (65)Zn in ZntA(-) Escherichia coli overexpressing NpunR4017 was reduced by up to 21 %, indicating the capacity for NpunR4017 to compensate for the loss of ZntA. These findings establish the newly identified NpunR4017 as a zinc efflux transporter and a key transporter for maintaining zinc homeostasis in N. punctiforme.

Changes in tree resistance, recovery and resilience across three successive extreme droughts in the northeast Iberian Peninsula.

PubMed

Serra-Maluquer, X; Mencuccini, M; Martínez-Vilalta, J

2018-05-01

Understanding which variables affect forest resilience to extreme drought is key to predict future dynamics under ongoing climate change. In this study, we analyzed how tree resistance, recovery and resilience to drought have changed along three consecutive droughts and how they were affected by species, tree size, plot basal area (as a proxy for competition) and climate. We focused on the three most abundant pine species in the northeast Iberian Peninsula: Pinus halepensis, P. nigra and P. sylvestris during the three most extreme droughts recorded in the period 1951-2010 (occurred in 1986, 1994, and 2005-2006). We cored trees from permanent sample plots and used dendrochronological techniques to estimate resistance (ability to maintain growth level during drought), recovery (growth increase after drought) and resilience (capacity to recover pre-drought growth levels) in terms of tree stem basal area increment. Mixed-effects models were used to determine which tree- and plot-level variables were the main determinants of resistance, recovery and resilience, and to test for differences among the studied droughts. Larger trees were significantly less resistant and resilient. Plot basal area effects were only observed for resilience, with a negative impact only during the last drought. Resistance, recovery and resilience differed across the studied drought events, so that the studied populations became less resistant, less resilient and recovered worse during the last two droughts. This pattern suggests an increased vulnerability to drought after successive drought episodes.

Conditionally reprogrammed normal and primary tumor prostate epithelial cells: a novel patient-derived cell model for studies of human prostate cancer

PubMed Central

Timofeeva, Olga A.; Palechor-Ceron, Nancy; Li, Guanglei; Yuan, Hang; Krawczyk, Ewa; Zhong, Xiaogang; Liu, Geng; Upadhyay, Geeta; Dakic, Aleksandra; Yu, Songtao; Fang, Shuang; Choudhury, Sujata; Zhang, Xueping; Ju, Andrew; Lee, Myeong-Seon; Dan, Han C.; Ji, Youngmi; Hou, Yong; Zheng, Yun-Ling; Albanese, Chris; Rhim, Johng; Schlegel, Richard; Dritschilo, Anatoly; Liu, Xuefeng

2017-01-01

Our previous study demonstrated that conditional reprogramming (CR) allows the establishment of patient-derived normal and tumor epithelial cell cultures from a variety of tissue types including breast, lung, colon and prostate. Using CR, we have established matched normal and tumor cultures, GUMC-29 and GUMC-30 respectively, from a patient's prostatectomy specimen. These CR cells proliferate indefinitely in vitro and retain stable karyotypes. Most importantly, only tumor-derived CR cells (GUMC-30) produced tumors in xenografted SCID mice, demonstrating maintenance of the critical tumor phenotype. Characterization of cells with DNA fingerprinting demonstrated identical patterns in normal and tumor CR cells as well as in xenografted tumors. By flow cytometry, both normal and tumor CR cells expressed basal, luminal, and stem cell markers, with the majority of the normal and tumor CR cells expressing prostate basal cell markers, CD44 and Trop2, as well as luminal marker, CD13, suggesting a transit-amplifying phenotype. Consistent with this phenotype, real time RT-PCR analyses demonstrated that CR cells predominantly expressed high levels of basal cell markers (KRT5, KRT14 and p63), and low levels of luminal markers. When the CR tumor cells were injected into SCID mice, the expression of luminal markers (AR, NKX3.1) increased significantly, while basal cell markers dramatically decreased. These data suggest that CR cells maintain high levels of proliferation and low levels of differentiation in the presence of feeder cells and ROCK inhibitor, but undergo differentiation once injected into SCID mice. Genomic analyses, including SNP and INDEL, identified genes mutated in tumor cells, including components of apoptosis, cell attachment, and hypoxia pathways. The use of matched patient-derived cells provides a unique in vitro model for studies of early prostate cancer. PMID:28009986

BLTK1 murine Leydig cells: a novel steroidogenic model for evaluating the effects of reproductive and developmental toxicants.

PubMed

Forgacs, Agnes L; Ding, Qi; Jaremba, Rosemary G; Huhtaniemi, Ilpo T; Rahman, Nafis A; Zacharewski, Timothy R

2012-06-01

Leydig cells are the primary site of androgen biosynthesis in males. Several environmental toxicants target steroidogenesis resulting in both developmental and reproductive effects including testicular dysgenesis syndrome. The aim of this study was to evaluate the effect of several structurally diverse endocrine disrupting compounds (EDCs) on steroidogenesis in a novel BLTK1 murine Leydig cell model. We demonstrate that BLTK1 cells possess a fully functional steroidogenic pathway that produces low basal levels of testosterone (T) and express all the necessary steroidogenic enzymes including Star, Cyp11a1, Cyp17a1, Hsd3b1, Hsd17b3, and Srd5a1. Recombinant human chorionic gonadotropin (rhCG) and forskolin (FSK) elicited concentration- and time-dependent induction of 3',5'-cyclic adenosine monophosphate, progesterone (P), and T, as well as the differential expression of Star, Hsd3b6, Hsd17b3, and Srd5a1 messenger RNA levels. The evaluation of several structurally diverse male reproductive toxicants including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), atrazine, prochloraz, triclosan, monoethylhexyl phthalate (MEHP), glyphosate, and RDX in BLTK1 cells suggests different modes of action perturb steroidogenesis. For example, prochloraz and triclosan antifungals reduced rhCG induction of T, consistent with published in vivo data but did not alter basal T levels. In contrast, atrazine and MEHP elicited modest induction of basal T but antagonized rhCG-mediated induction of T levels, whereas TCDD, glyphosate, and RDX had no effect on basal or rhCG induction of T in BLTK1 cells. These results suggest that BLTK1 cells maintain rhCG-inducible steroidogenesis and are a viable in vitro Leydig cell model to evaluate the effects of EDCs on steroidogenesis. This model can also be used to elucidate the different mechanisms underlying toxicant-mediated disruption of steroidogenesis.

Amino acids augment muscle protein synthesis in neonatal pigs during acute endotoxemia by stimulating mTOR-dependent translation initiation.

PubMed

Orellana, Renán A; Jeyapalan, Asumthia; Escobar, Jeffery; Frank, Jason W; Nguyen, Hanh V; Suryawan, Agus; Davis, Teresa A

2007-11-01

In skeletal muscle of adults, sepsis reduces protein synthesis by depressing translation initiation and induces resistance to branched-chain amino acid stimulation. Normal neonates maintain a high basal muscle protein synthesis rate that is sensitive to amino acid stimulation. In the present study, we determined the effect of amino acids on protein synthesis in skeletal muscle and other tissues in septic neonates. Overnight-fasted neonatal pigs were infused with endotoxin (LPS, 0 and 10 microg.kg(-1).h(-1)), whereas glucose and insulin were maintained at fasting levels; amino acids were clamped at fasting or fed levels. In the presence of fasting insulin and amino acids, LPS reduced protein synthesis in longissimus dorsi (LD) and gastrocnemius muscles and increased protein synthesis in the diaphragm, but had no effect in masseter and heart muscles. Increasing amino acids to fed levels accelerated muscle protein synthesis in LD, gastrocnemius, masseter, and diaphragm. LPS stimulated protein synthesis in liver, lung, spleen, pancreas, and kidney in fasted animals. Raising amino acids to fed levels increased protein synthesis in liver of controls, but not LPS-treated animals. The increase in muscle protein synthesis in response to amino acids was associated with increased mTOR, 4E-BP1, and S6K1 phosphorylation and eIF4G-eIF4E association in control and LPS-infused animals. These findings suggest that amino acids stimulate skeletal muscle protein synthesis during acute endotoxemia via mTOR-dependent ribosomal assembly despite reduced basal protein synthesis rates in neonatal pigs. However, provision of amino acids does not further enhance the LPS-induced increase in liver protein synthesis.

Control of arousal by the orexin neurons.

PubMed

Alexandre, Chloe; Andermann, Mark L; Scammell, Thomas E

2013-10-01

The orexin-producing neurons in the lateral hypothalamus play an essential role in promoting arousal and maintaining wakefulness. These neurons receive a broad variety of signals related to environmental, physiological and emotional stimuli; they project to almost every brain region involved in the regulation of wakefulness; and they fire most strongly during active wakefulness, high motor activation, and sustained attention. This review focuses on the specific neuronal pathways through which the orexin neurons promote wakefulness and maintain high level of arousal, and how recent studies using optogenetic and pharmacogenetic methods have demonstrated that the locus coeruleus, the tuberomammillary nucleus, and the basal forebrain are some of the key sites mediating the arousing actions of orexins. Copyright © 2013 Elsevier Ltd. All rights reserved.

Autophagy and Cancer

PubMed Central

Mah, Li Yen; Ryan, Kevin M.

2012-01-01

(Macro)autophagy is a cellular membrane trafficking process that serves to deliver cytoplasmic constituents to lysosomes for degradation. At basal levels, it is critical for maintaining cytoplasmic as well as genomic integrity and is therefore key to maintaining cellular homeostasis. Autophagy is also highly adaptable and can be modified to digest specific cargoes to bring about selective effects in response to numerous forms of intracellular and extracellular stress. It is not a surprise, therefore, that autophagy has a fundamental role in cancer and that perturbations in autophagy can contribute to malignant disease. We review here the roles of autophagy in various aspects of tumor suppression including the response of cells to nutrient and hypoxic stress, the control of programmed cell death, and the connection to tumor-associated immune responses. PMID:22166310

Brain-derived neurotrophic factor (BDNF) serum basal levels is not affected by power training in mobility-limited older adults - A randomized controlled trial.

PubMed

Hvid, L G; Nielsen, M K F; Simonsen, C; Andersen, M; Caserotti, P

2017-07-01

Brain-derived neurotrophic factor (BDNF) is a potential important factor involved in neuroplasticity, and may be a mediator for eliciting adaptations in neuromuscular function and physical function in older individuals following physical training. As power training taxes the neural system to a very high extent, it may be particularly effective in terms of eliciting increases in systemic BDNF levels. We examined the effects of 12weeks of power training on mature BDNF (mBDNF) and total BDNF (tBDNF) in mobility-limited older adults from the Healthy Ageing Network of Competence (HANC) study. We included 47 older men and women: n=22 in the training group (TG: progressive high intensity power training, 2 sessions per week; age 82.7±5.4years, 55% women) and n=25 in the control group (CG: no interventions; age 82.2±4.5years, 76% women). Following overnight fasting, basal serum levels of mBDNF and tBDNF were assessed (human ELISA kits) at baseline and post-intervention. At baseline, mBDNF and tBDNF levels were comparable in the two groups, TG and CG. Post-intervention, no significant within-group or between-group changes were observed in mBDNF or tBDNF. Moreover, when divided into responder tertiles based upon changes in mBDNF and tBDNF (i.e. decliners, maintainers, improvers), respectively, comparable findings were observed for TG and CG. Altogether, basal systemic levels of serum mBDNF and tBDNF are not affected in mobility-limited older adults following 12-weeks of power training, and do not appear to be a major mechanistic factor mediating neuroplasticity in mobility-limited older adults. Copyright © 2017 Elsevier Inc. All rights reserved.

Short-term ethanol exposure causes imbalanced neurotrophic factor allocation in the basal forebrain cholinergic system: a novel insight into understanding the initial processes of alcohol addiction.

PubMed

Miki, Takanori; Kusaka, Takashi; Yokoyama, Toshifumi; Ohta, Ken-ichi; Suzuki, Shingo; Warita, Katsuhiko; Jamal, Mostofa; Wang, Zhi-Yu; Ueki, Masaaki; Liu, Jun-Qian; Yakura, Tomiko; Tamai, Motoki; Sumitani, Kazunori; Hosomi, Naohisa; Takeuchi, Yoshiki

2014-02-01

Alcohol ingestion affects both motor and cognitive functions. One brain system that is influenced by ethanol is the basal forebrain (BF) cholinergic projection system, which projects to diverse neocortical and limbic areas. The BF is associated with memory and cognitive function. Our primary interest is the examination of how regions that receive BF cholinergic projections are influenced by short-term ethanol exposure through alterations in the mRNA levels of neurotrophic factors [nerve growth factor/TrkA, brain-derived neurotrophic factor/TrkB, and glial-derived neurotrophic factor (GDNF)/GDNF family receptor α1]. Male BALB/C mice were fed a liquid diet containing 5 % (v/v) ethanol. Pair-fed control mice were maintained on an identical liquid diet, except that the ethanol was isocalorically substituted with sucrose. Mice exhibiting signs of ethanol intoxication (stages 1-2) were used for real-time reverse transcription-polymerase chain reaction analyses. Among the BF cholinergic projection regions, decreased levels of GDNF mRNA and increased levels of TrkB mRNA were observed in the basal nucleus, and increased levels of TrkB mRNA were observed in the cerebral cortex. There were no significant alterations in the levels of expression of relevant neurotrophic factors in the septal nucleus and hippocampus. Given that neurotrophic factors function in retrograde/anterograde or autocrine/paracrine mechanisms and that BF cholinergic projection regions are neuroanatomically connected, these findings suggested that an imbalanced allocation of neurotrophic factor ligands and receptors is an initial phenomenon in alcohol addiction. The exact mechanisms underlying this phenomenon in the BF cholinergic system are unknown. However, our results provide a novel notion for the understanding of the initial processes in alcohol addiction.

Evaluation of basal sex hormone levels for activation of the hypothalamic-pituitary-gonadal axis.

PubMed

Ding, Yu; Li, Juan; Yu, Yongguo; Yang, Peirong; Li, Huaiyuan; Shen, Yongnian; Huang, Xiaodong; Liu, Shijian

2018-03-28

This study aimed to identify the predictive value of basal sex hormone levels for activation of the hypothalamic-pituitary-gonadal (HPG) axis in girls. Gonadotropin-releasing hormone (GnRH) stimulation tests were performed and evaluated in a total of 1750 girls with development of secondary sex characteristics. Correlation analyses were conducted between basal sex hormones and peak luteinizing hormone (LH) levels ≥5 IU/L during the GnRH stimulation test. Receiver operating characteristic (ROC) curves for basal levels of LH, follicle-stimulating hormone (FSH), LH/FSH, and estradiol (E2) before the GnRH stimulation test were plotted. The area under the curve (AUC) and 95% confidence intervals (CIs) were measured for each curve. The maximum AUC value was observed for basal LH levels (0.77, 95% CI: 0.74-0.79), followed by basal FSH levels (0.73, 95% CI: 0.70-0.75), the basal LH/FSH ratio (0.68, 95% CI: 0.65-0.71), and basal E2 levels (0.61, 95% CI: 0.59-0.64). The appropriate cutoff value of basal LH levels associated with a positive response of the GnRH stimulation test was 0.35 IU/L, with a sensitivity of 63.96% and specificity of 76.3% from the ROC curves when Youden's index showed the maximum value. When 100% of patients had peak LH levels ≥5 IU/L, basal LH values were >2.72 IU/L, but the specificity was only 5.45%. Increased basal LH levels are a significant predictor of a positive response during the GnRH stimulation test for assessing activation of the HPG axis in most girls with early pubertal signs.

Trait anxiety and ethanol: anxiolysis in high-anxiety mice and no relation to intake behavior in an addiction model.

PubMed

Correia, Diego; Ribeiro, Andrea Frozino; Brunialti Godard, Ana Lúcia; Boerngen-Lacerda, Roseli

2009-08-01

Anxiety has been proposed to play a role in the development of alcohol addiction, but the exact mechanisms by which this occurs remain unclear. The present study aimed to verify the relationship between basal anxiety levels, the anxiolytic-like effect of ethanol, and ethanol intake in mice exposed to an addiction model. In one experiment Swiss mice were characterized as high-anxiety (HA), medium-anxiety (MA), or non-anxiety (NA) in the elevated plus maze and then received saline or ethanol 2 g/kg acutely and chronically and were again exposed to the same test. NA mice decreased while MA mice maintained anxiety indices over the test days, regardless of treatment. HA ethanol-treated mice showed an anxiolytic-like effect, both acutely and chronically, while the saline-treated ones maintained their basal anxiety levels. In another experiment HA and MA mice were exposed to an addiction model based on a 3-bottle free-choice paradigm (ethanol 5% and 10%, and water) consisting of four phases: acquisition (10 weeks), withdrawal (W, 2 weeks), reexposure (2 weeks), and quinine-adulteration (2 weeks). HA and MA control mice had access only to water. Mice were characterized as addicted, heavy-drinker and light-drinker [Fachin-Scheit DJ, Ribeiro AF, Pigatto G, Goeldner FO, Boerngen-Lacerda R. Development of a mouse model of ethanol addiction: naltrexone efficacy in reducing consumption but not craving. J Neural Transm 2006;113:1305-21.]. No difference was observed between HA and MA mice in their preference for and intake of ethanol. No correlation was observed between ethanol intake, during any phase, and anxiety indices measured in the basal tests and during the W phase. The differences in anxiety indices between HA and MA groups persisted in the test performed during ethanol withdrawal, suggesting a "trait" anxiety profile. The data suggest that despite the fact that high anxiety trait levels are important for the anxiolytic-like effects of ethanol, they are not a determining factor for high ethanol intake, at least not under these experimental conditions.

Elevated basal progesterone levels are associated with increased preovulatory progesterone rise but not with higher pregnancy rates in ICSI cycles with GnRH antagonists.

PubMed

Mutlu, Mehmet Firat; Erdem, Mehmet; Mutlu, Ilknur; Bulut, Berk; Erdem, Ahmet

2017-09-01

To ascertain the association between basal progesterone (P) levels and the occurrence of preovulatory progesterone rise (PPR) and clinical pregnancy rates (CPRs) in ICSI cycles with GnRH antagonists. Serum P levels of 464 patients were measured on day 2 and day of hCG of cycles. Cycles with basal P levels>1.6ng/mL were cancelled. All embryos were cryopreserved in cycles with P levels≥2ng/mL on the day of hCG. The primary outcome measures were the incidence of PPR (P>1.5ng/mL) and CPR with regard to basal P. Basal P levels were significantly higher in cycles with PPR than in those without PPR (0.63±0.31 vs. 0.48±0.28ng/mL). Area under the curve for basal P according to ROC analysis to discriminate between elevated and normal P levels on the day of hCG was 0.65 (0.58-0.71 95% CI, p<0.01). The cut-off value for basal P levels that best discriminates between cycles with and without PPR was 0.65ng/mL. Cycles with basal P levels above 0.65ng/mL had a significantly higher incidence of PPR (30.9% vs. 13.5%) but similar clinical and cumulative pregnancy rates (38.8% vs. 31.1% and 41.7% vs. 32.6%, respectively) in comparison to cycles with basal P levels below 0.65ng/mL. In multivariate regression analysis, basal P levels, LH level on the first day of antagonist administration, and estradiol levels on the day of hCG trigger were the variables that predicted PPR. Basal P levels were associated with increased incidence of PPR but not with CPR. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of oxygen tension on bioenergetics and proteostasis in young and old myoblast precursor cells.

PubMed

Konigsberg, M; Pérez, V I; Ríos, C; Liu, Y; Lee, S; Shi, Y; Van Remmen, H

2013-01-01

In the majority of studies using primary cultures of myoblasts, the cells are maintained at ambient oxygen tension (21% O2), despite the fact that physiological O2 at the tissue level in vivo is much lower (~1-5% O2). We hypothesized that the cellular response in presence of high oxygen concentration might be particularly important in studies comparing energetic function or oxidative stress in cells isolated from young versus old animals. To test this, we asked whether oxygen tension plays a role in mitochondrial bioenergetics (oxygen consumption, glycolysis and fatty acid oxidation) or oxidative damage to proteins (protein disulfides, carbonyls and aggregates) in myoblast precursor cells (MPCs) isolated from young (3-4 m) and old (29-30 m) C57BL/6 mice. MPCs were grown under physiological (3%) or ambient (21%) O2 for two weeks prior to exposure to an acute oxidative insult (H2O2). Our results show significantly higher basal mitochondrial respiration in young versus old MPCs, an increase in basal respiration in young MPCs maintained at 3% O2 compared to cells maintained at 21% O2, and a shift toward glycolytic metabolism in old MPCs grown at 21% O2. H2O2 treatment significantly reduced respiration in old MPCs grown at 3% O2 but did not further repress respiration at 21% O2 in old MPCs. Oxidative damage to protein was higher in cells maintained at 21% O2 and increased in response to H2O2 in old MPCs. These data underscore the importance of understanding the effect of ambient oxygen tension in cell culture studies, in particular studies measuring oxidative damage and mitochondrial function.

Airway Basal Cell Heterogeneity and Lung Squamous Cell Carcinoma.

PubMed

Hynds, Robert E; Janes, Sam M

2017-09-01

Basal cells are stem/progenitor cells that maintain airway homeostasis, enact repair following epithelial injury, and are a candidate cell-of-origin for lung squamous cell carcinoma. Heterogeneity of basal cells is recognized in terms of gene expression and differentiation capacity. In this Issue, Pagano and colleagues isolate a subset of immortalized basal cells that are characterized by high motility, suggesting that they might also be heterogeneous in their biophysical properties. Motility-selected cells displayed an increased ability to colonize the lung in vivo The possible implications of these findings are discussed in terms of basal cell heterogeneity, epithelial cell migration, and modeling of metastasis that occurs early in cancer evolution. Cancer Prev Res; 10(9); 491-3. ©2017 AACR See related article by Pagano et al., p. 514 . ©2017 American Association for Cancer Research.

Serum Fetuin-A Levels in Patients with Bilateral Basal Ganglia Calcification.

PubMed

Demiryurek, Bekir Enes; Gundogdu, Asli Aksoy

2018-02-14

The idiopathic basal ganglia calcification (Fahr syndrome) may occur due to senility. Fetuin-A is a negative acute phase reactant which inhibits calcium-phosphorus precipitation and vascular calcification. In this study, we aimed to evaluate whether serum fetuin-A levels correlate with bilateral basal ganglia calcification. Forty-five patients who had bilateral basal ganglia calcification on brain CT were selected according to the inclusion and exclusion criteria, and 45 age and gender-matched subjects without basal ganglia calcification were included for the control group. Serum fetuin-A levels were measured from venous blood samples. All participants were divided into two groups; with and without basal ganglia calcification. These groups were divided into subgroups regarding age (18-32 and 33-45 years of age) and gender (male, female). We detected lower levels of serum fetuin-A in patients with basal ganglia calcification compared with the subjects without basal ganglia calcification. In all subgroups (female, male, 18-32 years and 33-45 years), mean fetuin-A levels were significantly lower in patients with basal ganglia calcification (p = 0.017, p = 0.014, p = 0.024, p = 0.026, p = 0.01 respectively). And statistically significantly lower levels of fetuin-A was found to be correlated with the increasing densities of calcification in the calcified basal ganglia group (p-value: <0.001). Considering the role of fetuin-A in tissue calcification and inflammation, higher serum fetuin-A levels should be measured in patients with basal ganglia calcification. We believe that the measurement of serum fetuin-A may play a role in the prediction of basal ganglia calcification as a biomarker. Copyright © 2017 Elsevier B.V. All rights reserved.

Lysyl oxidase-like 2 (LOXL2), a new regulator of cell polarity required for metastatic dissemination of basal-like breast carcinomas

PubMed Central

Moreno-Bueno, Gema; Salvador, Fernando; Martín, Alberto; Floristán, Alfredo; Cuevas, Eva P; Santos, Vanesa; Montes, Amalia; Morales, Saleta; Castilla, Maria Angeles; Rojo-Sebastián, Alejandro; Martínez, Alejandra; Hardisson, David; Csiszar, Katalin; Portillo, Francisco; Peinado, Héctor; Palacios, José; Cano, Amparo

2011-01-01

Basal-like breast carcinoma is characterized by the expression of basal/myoepithelial markers, undifferentiated phenotype, highly aggressive behaviour and frequent triple negative status (ESR−, PR−, Her2neu−). We have previously shown that epithelial–mesenchymal transition (EMT) occurs in basal-like breast tumours and identified Lysyl-oxidase-like 2 (LOXL2) as an EMT player and poor prognosis marker in squamous cell carcinomas. We now show that LOXL2 mRNA is overexpressed in basal-like human breast carcinomas. Breast carcinoma cell lines with basal-like phenotype show a specific cytoplasmic/perinuclear LOXL2 expression, and this subcellular distribution is significantly associated with distant metastatic incidence in basal-like breast carcinomas. LOXL2 silencing in basal-like carcinoma cells induces a mesenchymal-epithelial transition (MET) associated with a decrease of tumourigenicity and suppression of metastatic potential. Mechanistic studies indicate that LOXL2 maintains the mesenchymal phenotype of basal-like carcinoma cells by a novel mechanism involving transcriptional downregulation of Lgl2 and claudin1 and disorganization of cell polarity and tight junction complexes. Therefore, intracellular LOXL2 is a new candidate marker of basal-like carcinomas and a target to block metastatic dissemination of this aggressive breast tumour subtype. PMID:21732535

Physiological stimuli evoke two forms of endocytosis in bovine chromaffin cells.

PubMed

Chan, S A; Smith, C

2001-12-15

1. Exocytosis and endocytosis were measured following single, or trains of, simulated action potentials (sAP) in bovine adrenal chromaffin cells. Catecholamine secretion was measured by oxidative amperometry and cell membrane turnover was measured by voltage clamp cell capacitance measurements. 2. The sAPs evoked inward Na(+) and Ca(2+) currents that were statistically identical to those evoked by native action potential waveforms. On average, a single secretory granule underwent fusion following sAP stimulation. An equivalent amount of membrane was then quickly internalised (tau = 560 ms). 3. Stimulation with sAP trains revealed a biphasic relationship between cell firing rate and endocytic activity. At basal stimulus frequencies (single to 0.5 Hz) cells exhibited a robust membrane internalisation that then diminished as firing increased to intermediate levels (1.9 and 6 Hz). However at the higher stimulation rates (10 and 16 Hz) endocytic activity rebounded and was again able to effectively maintain cell surface near pre-stimulus levels. 4. Treatment with cyclosporin A and FK506, inhibitors of the phosphatase calcineurin, left endocytosis characteristics unaltered at the lower basal stimulus levels, but blocked the resurgence in endocytosis seen in control cells at higher sAP frequencies. 5. Based on these findings we propose that, under physiological electrical stimulation, chromaffin cells internalise membrane via two distinct pathways that are separable. One is prevalent at basal stimulus frequencies, is lessened with increased firing, and is insensitive to cyclosporin A and FK506. A second endocytic form is activated by increased firing frequencies, and is selectively blocked by cyclosporin A and FK506.

Physiological stimuli evoke two forms of endocytosis in bovine chromaffin cells

PubMed Central

Chan, Shyue-An; Smith, Corey

2001-01-01

Exocytosis and endocytosis were measured following single, or trains of, simulated action potentials (sAP) in bovine adrenal chromaffin cells. Catecholamine secretion was measured by oxidative amperometry and cell membrane turnover was measured by voltage clamp cell capacitance measurements. The sAPs evoked inward Na+ and Ca2+ currents that were statistically identical to those evoked by native action potential waveforms. On average, a single secretory granule underwent fusion following sAP stimulation. An equivalent amount of membrane was then quickly internalised (τ = 560 ms). Stimulation with sAP trains revealed a biphasic relationship between cell firing rate and endocytic activity. At basal stimulus frequencies (single to 0.5 Hz) cells exhibited a robust membrane internalisation that then diminished as firing increased to intermediate levels (1.9 and 6 Hz). However at the higher stimulation rates (10 and 16 Hz) endocytic activity rebounded and was again able to effectively maintain cell surface near pre-stimulus levels. Treatment with cyclosporin A and FK506, inhibitors of the phosphatase calcineurin, left endocytosis characteristics unaltered at the lower basal stimulus levels, but blocked the resurgence in endocytosis seen in control cells at higher sAP frequencies. Based on these findings we propose that, under physiological electrical stimulation, chromaffin cells internalise membrane via two distinct pathways that are separable. One is prevalent at basal stimulus frequencies, is lessened with increased firing, and is insensitive to cyclosporin A and FK506. A second endocytic form is activated by increased firing frequencies, and is selectively blocked by cyclosporin A and FK506. PMID:11744761

A Device that Allows Rodents to Behaviorally Thermoregulate when Housed in Vivariums

EPA Science Inventory

Laboratories and vivariums are maintained at ambient temperatures (Ta) of 20-24 ⁰C and it is widely accepted that mice maintained under these conditions are cold stressed. When mice are inactive and sleeping in the daytime, their zone of thermoneutrality associated with a basal m...

New Basal Insulins: a Clinical Perspective of Their Use in the Treatment of Type 2 Diabetes and Novel Treatment Options Beyond Basal Insulin.

PubMed

Frias, Patrick F; Frias, Juan Pablo

2017-08-18

The purpose of this review was to review advances in basal insulin formulations and new treatment options for patients with type 2 diabetes not achieving glycemic targets despite optimized basal insulin therapy. Advances in basal insulin formulations have resulted in products with increasingly favorable pharmacokinetic and pharmacodynamic properties, including flatter, peakless action profiles, less inter- and intra-patient variability, and longer duration of activity. These properties have translated to significantly reduced risk of hypoglycemia (particularly during the night) compared with previous generation basal insulins. When optimized basal insulin therapy is not sufficient to obtain or maintain glycemic goals, various options exist to improve glycemic control, including intensification of insulin therapy with the addition of prandial insulin or changing to pre-mixed insulin and, more recently, the addition of a GLP-1 receptor agonist, either as a separate injection or as a component of one of the new fixed-ratio combinations of a basal insulin and GLP-1 RA. New safer and often more convenient basal insulins and fixed ratio combinations containing basal insulin (and GLP-1 receptor agonist) are available today for patients with type 2 diabetes not achieving glycemic goals. Head-to-head studies comparing the latest generation basal insulins are underway, and future studies assessing the fixed-ratio combinations will be important to better understand their differentiating features.

Heat and moisture exchangers and heated humidifiers in acute lung injury/acute respiratory distress syndrome patients. Effects on respiratory mechanics and gas exchange.

PubMed

Morán, Indalecio; Bellapart, Judith; Vari, Alessandra; Mancebo, Jordi

2006-04-01

To compare, in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) patients, the short-term effects of heat and moisture exchangers (HME) and heated humidifiers (HH) on gas exchange, and also on respiratory system mechanics when isocapnic conditions are met. Prospective open clinical study. Intensive Care Service. Seventeen invasively ventilated ALI/ARDS patients. The study was performed in three phases: (1) determinations were made during basal ventilatory settings with HME; (2) basal ventilatory settings were maintained and HME was replaced by an HH; (3) using the same HH, tidal volume (Vt) was decreased until basal PaCO2 levels were reached. FiO2, respiratory rate and PEEP were kept unchanged. Respiratory mechanics, Vdphys, gas exchange and hemodynamic parameters were obtained at each phase. By using HH instead of HME and without changing Vt, PaCO2 decreased from 46+/-9 to 40+/-8 mmHg (p<0.001) and Vdphys decreased from 352+/-63 to 310+/-74 ml (p<0.001). Comparing the first phase with the third, Vt decreased from 521+/-106 to 440+/-118 ml (p<0.001) without significant changes in PaCO2, Vd/Vt decreased from 0.69+/-0.11 to 0.62+/-0.12 (p<0.001), plateau airway pressure decreased from 25+/-6 to 21+/-6 cmH2O (p<0.001) and respiratory system compliance improved from 35+/-12 to 42+/-15 ml/cmH2O (p<0.001). PaO2 remained unchanged in the three phases. Reducing dead space with the use of HH decreases PaCO2 and more importantly, if isocapnic conditions are maintained by reducing Vt, this strategy improves respiratory system compliance and reduces plateau airway pressure.

Terminal zone glacial sediment transfer at a temperate overdeepened glacier system

NASA Astrophysics Data System (ADS)

Swift, D. A.; Cook, S. J.; Graham, D. J.; Midgley, N. G.; Fallick, A. E.; Storrar, R.; Toubes Rodrigo, M.; Evans, D. J. A.

2018-01-01

Continuity of sediment transfer through glacial systems is essential to maintain subglacial bedrock erosion, yet transfer at temperate glaciers with overdeepened beds, where subglacial fluvial sediment transport should be greatly limited by adverse slopes, remains poorly understood. Complex multiple transfer processes in temperate overdeepened systems has been indicated by the presence of large frontal moraine systems, supraglacial debris of mixed transport origin, thick basal ice sequences, and englacial thrusts and eskers. At Svínafellsjökull, thrusts comprising decimetre-thick debris-rich bands of stratified facies ice of basal origin, with a coarser size distribution and higher clast content than that observed in basal ice layers, contribute substantially to the transfer of subglacial material in the terminal zone. Entrainment and transfer of material occurs by simple shear along the upper surface of bands and by strain-induced deformation of stratified and firnified glacier ice below. Thrust material includes rounded and well-rounded clasts that are also striated, indicating that fluvial bedload is deposited as subglacial channels approach the overdeepening and then entrained along thrusts. Substantial transfer also occurs within basal ice, with facies type and debris content dependent on the hydrological connectedness of the adverse slope. A process model of transfer at glaciers with terminal overdeepenings is proposed, in which the geometry of the overdeepening influences spatial patterns of ice deformation, hydrology, and basal ice formation. We conclude that the significance of thrusting in maintaining sediment transfer continuity has likely been overlooked by glacier sediment budgets and glacial landscape evolution studies.

Age-related impairment in choroidal blood flow compensation for arterial blood pressure fluctuation in pigeons.

PubMed

Reiner, Anton; Del Mar, Nobel; Zagvazdin, Yuri; Li, Chunyan; Fitzgerald, Malinda E C

2011-09-14

Choroidal vessels compensate for changes in systemic blood pressure (BP) so that choroidal blood flow (ChBF) remains stable over a BP range of approximately 40 mm Hg above and below basal. Because of the presumed importance of ChBF regulation for maintenance of retinal health, we investigated if ChBF compensation for BP fluctuation in pigeons fails with age. Transcleral laser Doppler flowmetry was used to measure ChBF during spontaneous BP fluctuation in anesthetized pigeons ranging in age from 0.5 to 17 years (pigeons can live approximately 20 years in captivity). ChBF in <8-year-old pigeons remained near 100% of basal ChBF at BPs ranging 40 mm Hg above and below basal BP (95 mm Hg). Baroregulation failed below approximately 50 mm Hg BP. In ≥8-year-old pigeons, ChBF compensation was absent at >90 mm Hg BP, with ChBF linearly following BP. Over the 60 to 90 mm Hg range, ChBF in ≥8-year-old pigeons was maintained at 60-70% of young basal ChBF. Below approximately 55 mm Hg, baroregulation again followed BP linearly. Age-related ChBF baroregulatory impairment occurs in pigeons, with ChBF linear with above-basal BP, and ChBF failing to adequately maintain ChBF during below-basal BP. Defective autonomic sympathetic and parasympathetic neurogenic control, or defective myogenic control, may cause these baroregulatory defects. In either case, overperfusion during high BP may cause oxidative injury to the outer retina, whereas underperfusion during low BP may result in deficient nutrient supply and waste removal, with both abnormalities contributing to age-related retinal pathology and vision loss.

Differentiation Generates Paracrine Cell Pairs That Maintain Basaloid Mouse Mammary Tumors: Proof of Concept

PubMed Central

Kim, Soyoung; Goel, Shruti; Alexander, Caroline M.

2011-01-01

There is a paradox offered up by the cancer stem cell hypothesis. How are the mixed populations that are characteristic of heterogeneous solid tumors maintained at constant proportion, given their high, and different, mitotic indices? In this study, we evaluate a well-characterized mouse model of human basaloid tumors (induced by the oncogene Wnt1), which comprise mixed populations of mammary epithelial cells resembling their normal basal and luminal counterparts. We show that these cell types are substantially inter-dependent, since the MMTV LTR drives expression of Wnt1 ligand in luminal cells, whereas the functional Wnt1-responsive receptor (Lrp5) is expressed by basal cells, and both molecules are necessary for tumor growth. There is a robust tumor initiating activity (tumor stem cell) in the basal cell population, which is associated with the ability to differentiate into luminal and basal cells, to regenerate the oncogenic paracrine signaling cell pair. However, we found an additional tumor stem cell activity in the luminal cell population. Knowing that tumors depend upon Wnt1-Lrp5, we hypothesized that this stem cell must express Lrp5, and found that indeed, all the stem cell activity could be retrieved from the Lrp5-positive cell population. Interestingly, this reflects post-transcriptional acquisition of Lrp5 protein expression in luminal cells. Furthermore, this plasticity of molecular expression is reflected in plasticity of cell fate determination. Thus, in vitro, Wnt1-expressing luminal cells retro-differentiate to basal cell types, and in vivo, tumors initiated with pure luminal cells reconstitute a robust basal cell subpopulation that is indistinguishable from the populations initiated by pure basal cells. We propose this is an important proof of concept, demonstrating that bipotential tumor stem cells are essential in tumors where oncogenic ligand-receptor pairs are separated into different cell types, and suggesting that Wnt-induced molecular and fate plasticity can close paracrine loops that are usually separated into distinct cell types. PMID:21541292

Erosional development of bedrock spur and gully topography in the Valles Marineris, Mars

NASA Technical Reports Server (NTRS)

Patton, Peter C.

1990-01-01

Gully networks separated by resistant bedrock spurs are a common erosional feature along the escarpments that border the Valles Marineris. The resistant spur topography is best developed where the base of the slope is truncated by linear scarps interpreted as fault scarps. Regional variations in slope morphology imply that spur and gully topography undergoes a systematic progressive degradation through time associated with the erosional destruction of the basal fault scarps. The comparative morphometry of the divide networks indicates that the density of the spur networks and the number of first-order unbranched spurs decreases as the basal slope break becomes more sinuous. Abstraction of the spurs occurs through regolith storage in adjacent gullies at the slope base and the most degraded slope forms are entirely buried in talus. The basal fault scarps apparently control regolith transport by allowing debris to drain from the slope. As these basal scarps decay the slope base becomes increasingly sinuous and the slopes become transport limited. Dry mass-wasting may be the most important process acting on these slopes where a continually lowered base level is required to maintain the spur topography. In contrast to the Martian slopes, range front fault escarpments in the western U.S. show no systematic trend in spur network geometry as they are eroded. These weathering limited slopes are controlled by the more efficient removal of regolith through fluvial processes which rapidly create quasi-equilibrium drainage networks.

Differential responses of juvenile and adult South African abalone (Haliotis midae Linnaeus) to low and high oxygen levels.

PubMed

Vosloo, Andre; Laas, Anél; Vosloo, Dalene

2013-01-01

Marine invertebrates have evolved multiple responses to naturally variable environmental oxygen, all aimed at either maintaining cellular oxygen homeostasis or limiting cellular damage during or after hypoxic or hyperoxic events. We assessed organismal (rates of oxygen consumption and ammonia excretion) and cellular (heat shock protein expression, anti-oxidant enzymes) responses of juvenile and adult abalone exposed to low (~83% of saturation), intermediate (~95% of saturation) and high (~115% of saturation) oxygen levels for one month. Using the Comet assay, we measured DNA damage to determine whether the observed trends in the protective responses were sufficient to prevent oxidative damage to cells. Juveniles were unaffected by moderately hypoxic and hyperoxic conditions. Elevated basal rates of superoxide dismutase, glutathione peroxidase and catalase were sufficient to prevent DNA fragmentation and protein damage. Adults, with their lower basal rate of anti-oxidant enzymes, had increased DNA damage under hypoxic and hyperoxic conditions, indicating that the antioxidant enzymes were unable to prevent oxidative damage under hypoxic and hyperoxic conditions. The apparent insensitivity of juvenile abalone to decreased and increased oxygen might be related to their life history and development in algal and diatom biofilms where they are exposed to extreme diurnal fluctuations in dissolved oxygen levels. Copyright © 2012 Elsevier Inc. All rights reserved.

Breast-feeding and postpartum ovulation.

PubMed

Howie, P W; Mcneilly, A S

1982-04-01

This paper reviews the evidence for the contraceptive effects of breastfeeding on postpartum ovulation. In developing countries breastfeeding prevents more pregnancies than all the other methods of contraception. In a detailed Edinburgh longitudinal study of 27 breastfeeding and 10 bottlefeeding mothers, the return of ovarian follicular development and ovulation was determined by several estimations of total urinary estrogen and pregnanedial excretion, respectively. In the bottlefeeding mothers the patterns of events after delivery was consistent. Basal prolactin levels fell to non-pregnant levels within 2-3 weeks postpartum. By 15 weeks all bottlefeeding mothers had resumed ovulation and menstruation. By contrast, all breastfeeding mothers who breastfed for a mean of 40 weeks maintained elevated basal prolactin levels for longer than the bottlefeeders. The mean time to 1st ovulation was 36 weeks with a range between 15-66 weeks postpartum. The infant feeding patterns showed striking differences between these mothers (33% of the whole group) who suppressed ovulation for more than 40 weeks postpartum and the rest of the mothers (67%) who ovulated before that time. The mothers who suppressed ovulation for more than 40 weeks not only maintained breastfeeding for the greatest number of weeks, but also suckled more frequently, breastfed for a longer total time each day, and maintained 1 or more night feeds for a longer time. After supplementary food was given there was a rapid increase in the number of mothers with evidence of ovarian activity and within 16 weeks of starting, 71% had evidence of follicular activity and 52% had ovulated. Mothers who introduce weaning food abruptly and reduce sucking rapidly will be more likely to experience an early return of ovulation and potential fertility. The mechanism of lactational infertility is not clearly understood. 45% of the completed menstrual cycles during lactation were anovular and of the 55% which were ovular, many were associated with defective luteal phases. The birth spacing effect of lactation is of great importance in communities where alternative contraceptive devices are not available or not acceptable. Breastfeeding is a complementary form of contraception.

Site, gender and age variation in normal skin colour on the back and the forearm: tristimulus colorimeter measurements.

PubMed

Fullerton, A; Serup, J

1997-02-01

To study whether anatomical location and age and gender of subjects had any influence on the objective skin colour measurements. Baseline colour in prone position was measured with the Minolta ChromaMeter® in the upper, middle and lower level of the upper back and on the forearm of 168 volunteers. These two sites are commonly used in skin testing. Higher basal a* and lower basal L* levels were found on the upper scapular region compared to the lower scapular region and the subscapular region. The basal b* level showed no variation relative to site. The basal a* and the basal b* levels were lower on the forearm compared to the upper back while the basal L* level was higher. Females above 65 years showed a less coloured skin with lower values as compared to those of younger age. Females were found to have a generally lower basal a* level than males both on the upper back and forearm skin. These relatively major differences and sources of variation have to be considered when planning irritancy studies where colour differences between erythema and normal skin is used.

Elucidating the Tumor Suppressive Role of SLITs in Maintaining the Basal Cell Niche

DTIC Science & Technology

2009-07-01

deregulated upon cancerous transformation. 15. SUBJECT TERMS breast , Slit2, Robo1, basal cell 16. SECURITY CLASSIFICATION OF: 17. LIMITATION...natural
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 maintain
 breast 
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SLITs
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 secreted
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Dioxin Receptor Expression Inhibits Basal and Transforming Growth Factor β-induced Epithelial-to-mesenchymal Transition*

PubMed Central

Rico-Leo, Eva M.; Alvarez-Barrientos, Alberto; Fernandez-Salguero, Pedro M.

2013-01-01

Recent studies have emphasized the role of the dioxin receptor (AhR) in maintaining cell morphology, adhesion, and migration. These novel AhR functions depend on the cell phenotype, and although AhR expression maintains mesenchymal fibroblasts migration, it inhibits keratinocytes motility. These observations prompted us to investigate whether AhR modulates the epithelial-to-mesenchymal transition (EMT). For this, we have used primary AhR+/+ and AhR−/− keratinocytes and NMuMG cells engineered to knock down AhR levels (sh-AhR) or to express a constitutively active receptor (CA-AhR). Both AhR−/− keratinocytes and sh-AhR NMuMG cells had increased migration, reduced levels of epithelial markers E-cadherin and β-catenin, and increased expression of mesenchymal markers Snail, Slug/Snai2, vimentin, fibronectin, and α-smooth muscle actin. Consistently, AhR+/+ and CA-AhR NMuMG cells had reduced migration and enhanced expression of epithelial markers. AhR activation by the agonist FICZ (6-formylindolo[3,2-b]carbazole) inhibited NMuMG migration, whereas the antagonist α-naphthoflavone induced migration as did AhR knockdown. Exogenous TGFβ exacerbated the promigratory mesenchymal phenotype in both AhR-expressing and AhR-depleted cells, although the effects on the latter were more pronounced. Rescuing AhR expression in sh-AhR cells reduced Snail and Slug/Snai2 levels and cell migration and restored E-cadherin levels. Interference of AhR in human HaCaT cells further supported its role in EMT. Interestingly, co-immunoprecipitation and immunofluorescence assays showed that AhR associates in common protein complexes with E-cadherin and β-catenin, suggesting the implication of AhR in cell-cell adhesion. Thus, basal or TGFβ-induced AhR down-modulation could be relevant in the acquisition of a motile EMT phenotype in both normal and transformed epithelial cells. PMID:23382382

Functions of transmembrane domain 3 of human melanocortin-4 receptor.

PubMed

Mo, Xiu-Lei; Yang, Rui; Tao, Ya-Xiong

2012-12-01

The melanocortin-4 receptor (MC4R) is a G protein-coupled receptor critical for maintaining energy homeostasis. Transmembrane domain 3 (TM3) of MC4R contains residues that were suggested to be essential in ligand binding and signaling. Several MC4R mutations in TM3 are associated with human obesity. To gain a better understanding of the functions of TM3, we analyzed the functions of 26 residues in TM3 using alanine-scanning mutagenesis. We showed that all mutants had normal cell-surface expression. Four mutants were defective in ligand binding and signaling and six mutants had normal ligand binding but impaired cAMP production. L140A had increased basal cAMP level. To further characterize the function of L140, we generated 17 additional L140 mutants. Fifteen L140 mutants had significantly decreased cell-surface expression, with L140R and L140V expressed normally. Ten L140 mutants had increased basal cAMP activities. Four L140 mutants were defective in ligand-stimulated cAMP generation. Interestingly, with the ERK1/2 pathway, we showed that nine constitutively active mutants had similar levels of basal pERK1/2 as that of WT, and two signaling defective mutants had similar levels of pERK1/2 as that of WT upon agonist stimulation, different from their cAMP signaling properties, suggesting biased signaling in these mutant receptors. In summary, we identified 13 residues in TM3 that were essential for ligand binding and/or signaling. Moreover, L140 was critical for locking MC4R in inactive conformation and several mutants showed biased signaling in cAMP and ERK1/2 signaling pathways.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thein, Soe; Pham, Anna; Bayer, K. Ulrich

Highlights: • CYLD is phosphorylated by IKK in isolated PSDs in the absence of Ca{sup 2+}. • CYLD is phosphorylated by IKK at the PSDs of intact neurons in basal conditions. • Phosphorylation of CYLD by IKK increases its deubiquitinase activity. • The process is likely to influence protein trafficking at the PSD in basal conditions. - Abstract: K63-linked polyubiquitination of proteins regulates their trafficking into specific cellular pathways such as endocytosis and autophagy. CYLD, a deubiquitinase specific for K63-linked polyubiquitins, is present in high quantities at the postsynaptic density (PSD). It was previously shown that, under excitatory conditions, CaMKIImore » activates CYLD in a Ca{sup 2+}-dependent manner. The observation that CYLD can also be phosphorylated in the absence of Ca{sup 2+} in isolated PSDs led us to further explore the regulation of CYLD under basal conditions. A possible involvement of the autonomous form of CaMKII and IKK, both kinases known to be localized at the PSD, was examined. A CaMKII inhibitor CN21 had no effect on CYLD phosphorylation in the absence of Ca{sup 2+}, but two different IKK inhibitors, IKK16 and tatNEMO, inhibited its phosphorylation. Immuno-electron microscopy on hippocampal cultures, using an antibody for CYLD phosphorylated at S-418, revealed that the phosphorylated form of CYLD is present at the PSD under basal conditions. Phosphorylation of CYLD under basal conditions was inhibited by IKK16. NMDA treatment further promoted phosphorylation of CYLD at the PSD, but IKK16 failed to block the NMDA-induced effect. In vitro experiments using purified proteins demonstrated direct phosphorylation and activation of CYLD by the beta catalytic subunit of IKK. Activation of IKK in isolated PSDs also promoted phosphorylation of CYLD and an increase in endogenous deubiquitinase activity for K63-linked polyubiquitins. Altogether, the results suggest that in the absence of excitatory conditions, constitutive IKK activity at the PSD regulates CYLD and maintains basal levels of K63-linkage specific deubiquitination at the synapse.« less

Niche-induced cell death and epithelial phagocytosis regulate hair follicle stem cell pool.

PubMed

Mesa, Kailin R; Rompolas, Panteleimon; Zito, Giovanni; Myung, Peggy; Sun, Thomas Y; Brown, Samara; Gonzalez, David G; Blagoev, Krastan B; Haberman, Ann M; Greco, Valentina

2015-06-04

Tissue homeostasis is achieved through a balance of cell production (growth) and elimination (regression). In contrast to tissue growth, the cells and molecular signals required for tissue regression remain unknown. To investigate physiological tissue regression, we use the mouse hair follicle, which cycles stereotypically between phases of growth and regression while maintaining a pool of stem cells to perpetuate tissue regeneration. Here we show by intravital microscopy in live mice that the regression phase eliminates the majority of the epithelial cells by two distinct mechanisms: terminal differentiation of suprabasal cells and a spatial gradient of apoptosis of basal cells. Furthermore, we demonstrate that basal epithelial cells collectively act as phagocytes to clear dying epithelial neighbours. Through cellular and genetic ablation we show that epithelial cell death is extrinsically induced through transforming growth factor (TGF)-β activation and mesenchymal crosstalk. Strikingly, our data show that regression acts to reduce the stem cell pool, as inhibition of regression results in excess basal epithelial cells with regenerative abilities. This study identifies the cellular behaviours and molecular mechanisms of regression that counterbalance growth to maintain tissue homeostasis.

Repeated immobilization stress increases uncoupling protein 1 expression and activity in Wistar rats.

PubMed

Gao, Bihu; Kikuchi-Utsumi, Kazue; Ohinata, Hiroshi; Hashimoto, Masaaki; Kuroshima, Akihiro

2003-06-01

Repeat immobilization-stressed rats are leaner and have improved cold tolerance due to enhancement of brown adipose tissue (BAT) thermogenesis. This process likely involves stress-induced sympathetic nervous system activation and adrenocortical hormone release, which dynamically enhances and suppresses uncoupling protein 1 (UCP1) function, respectively. To investigate whether repeated immobilization influences UCP1 thermogenic properties, we assessed UCP1 mRNA, protein expression, and activity (GDP binding) in BAT from immobilization-naive or repeatedly immobilized rats (3 h daily for 4 weeks) and sham operated or adrenalectomized (ADX) rats. UCP1 properties were assessed before (basal) and after exposure to 3 h of acute immobilization. Basal levels of GDP binding and UCP1 expression was significantly increased (140 and 140%) in the repeated immobilized group. Acute immobilization increased GDP binding in both naive (180%) and repeated immobilized groups (220%) without changing UCP1 expression. In ADX rats, basal GDP binding and UCP1 gene expression significantly increased (140 and 110%), and acute immobilization induced further increase. These data demonstrate that repeated immobilization resulted in enhanced UCP1 function, suggesting that enhanced BAT thermogenesis contributes to lower body weight gain through excess energy loss and an improved ability to maintain body temperature during cold exposure.

Activation of Basal Gluconeogenesis by Coactivator p300 Maintains Hepatic Glycogen Storage

PubMed Central

Cao, Jia; Meng, Shumei; Ma, Anlin; Radovick, Sally; Wondisford, Fredric E.

2013-01-01

Because hepatic glycogenolysis maintains euglycemia during early fasting, proper hepatic glycogen synthesis in the fed/postprandial states is critical. It has been known for decades that gluconeogenesis is essential for hepatic glycogen synthesis; however, the molecular mechanism remains unknown. In this report, we show that depletion of hepatic p300 reduces glycogen synthesis, decreases hepatic glycogen storage, and leads to relative hypoglycemia. We previously reported that insulin suppressed gluconeogenesis by phosphorylating cAMP response element binding protein-binding protein (CBP) at S436 and disassembling the cAMP response element-binding protein-CBP complex. However, p300, which is closely related to CBP, lacks the corresponding S436 phosphorylation site found on CBP. In a phosphorylation-competent p300G422S knock-in mouse model, we found that mutant mice exhibited reduced hepatic glycogen content and produced significantly less glycogen in a tracer incorporation assay in the postprandial state. Our study demonstrates the important and unique role of p300 in glycogen synthesis through maintaining basal gluconeogenesis. PMID:23770612

Correlation Between Personality Traits and Testosterone Concentrations in Healthy Population.

PubMed

Tajima-Pozo, Kazuhiro; Bayón, Camila; Díaz-Marsá, Marina; Carrasco, Jose Luis

2015-01-01

High plasma testosterone levels have been associated with aggression, sexual behaviour and social status. The aim of this paper was to study the correlation between basal plasma testosterone levels and personality variables in healthy participants. Fifty-four participants were randomly enrolled into this study. Basal plasma testosterone levels were measured between 8:30 am and 10 am. After 24 hours of blood drawing, each subject completed personality questionnaires. Positive correlation between basal plasma testosterone levels and anti-social personality traits in both genders was observed (r = 0.336 and P < 0.018). Also, a positive correlation was observed between basal plasmatestosterone levels and criminal thinking traits (r = 0. 376, P < 0.05) and Millon compulsive (r = 0.386, P < 0.010) in both genders. In female participants, a positive correlation between basal plasmatestosterone levels and psychoticism (r = 0. 25, P < 0.019) and Cloninger AUTO TCI (r = 0.507, P < 0.004) was observed. In males participants positive correlation between baseline plasmatic Testosterone levels and Millon Antisocial trait (r = 0. 544, P < 0.19) and Millon Hypomania trait (r = 0. 485, P < 0.41) and Millon Drug Abuse trait (r = 0.632, P < 0.05) was reported. Our results suggest gender differences in clinical and personality variables related with basal plasma testosterone level. In men, high plasma testosterone levels were associated with clinical traits, substance abuse and hypomania. Women with higher basal testosterone levels showed higher scores on personality self-direction traits.

Differentiation of anchoring junctions in tracheal basal cells in the growing rat.

PubMed

Evans, M J; Cox, R A; Burke, A S; Moller, P C

1992-02-01

A function of airway basal cells is to attach ciliated and nonciliated columnar cells to the basal lamina. The significance of the basal cell in attachment is related to the height of the columnar epithelium. In taller epithelia, basal cells are more numerous and differentiated with respect to anchoring junctional adhesion mechanisms (desmosomes, hemidesmosomes, and the cytoskeleton) than in shorter epithelia. In this study, we determined if basal cell anchoring junctional adhesion mechanisms differentiated during growth of the airway. Tracheas from five 3-day-old, five 30-day-old, and five 90-day-old rats were prepared for electron microscopy and morphometrically studied by standard techniques. The circumference of the trachea increased from 2.5 +/- 0.2 to 7.5 +/- 0.4 mm during growth. The height of the columnar cell increased from 13.4 +/- 1.5 to 24.6 +/- 3.9 microns, and the number of basal cells per millimeter increased from 3.2 +/- 0.7 to 9.6 +/- 1.8 during growth. The number of desmosomes per basal cell profile increased significantly from 1.5 +/- 0.1 to 2.1 +/- 0.1, as did keratin filament volume density from 0.046 +/- 0.05 to 0.098 +/- 0.032. The amount of hemidesmosome attachment per basal cell did not increase significantly during growth of the airway. These data demonstrate that as tracheas grow in circumference, the columnar cells increase in height, basal cells increase in number, and anchoring junctional adhesion mechanisms differentiate in the basal cells. These changes are closely related to the height of the epithelium and result in maintaining a constant amount of attachment between the columnar epithelium and the basal lamina as the epithelium increases in height.

Change in hexose distribution volume and fractional utilization of ( sup 18 F)-2-deoxy-2-fluoro-D-glucose in brain during acute hypoglycemia in humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shapiro, E.T.; Cooper, M.; Chen, C.T.

1990-02-01

We used positron emission tomography (PET) to study the effects of mild hypoglycemia on cerebral glucose uptake and metabolism. Nine healthy men were studied under basal saline-infusion conditions, and during euglycemic and hypoglycemic clamp studies. Insulin was infused at the same rate (1 mU.kg-1.min-1) in both clamp studies. In euglycemic clamp studies, glucose was infused at a rate sufficient to maintain the basal plasma glucose concentration, whereas in hypoglycemic clamp studies, the glucose infusion rate was reduced to maintain the plasma glucose at 3.1 mM. Each study lasted 3 h and included a 30-min baseline period and a subsequent 150-minmore » period in which insulin or glucose was administered. Blood samples for measurement of insulin, glucose, cortisol, growth hormone, and glucagon were obtained at 20- to 30-min intervals. A bolus injection of 5-10 mCi (18F)-2-deoxy-2-fluoro-D-glucose (2-DFG) was administered 120 min after initiation of the study, and plasma radioactivity and dynamic PET scans were obtained at frequent intervals for the remaining 40-60 min of the study. Cerebral regions of interest were defined, and concentrations of radioactivity were calculated and used in the three-compartment model of 2-DFG distribution described by Sokoloff. Glucose levels were similar during saline-infusion (4.9 +/- 0.1 mM) and euglycemic clamp (4.8 +/- 0.1 mM) studies, whereas the desired degree of mild hypoglycemia was achieved during the hypoglycemic clamp study (3.1 +/- 0.1 mM, P less than 0.05). The insulin level during saline infusion was 41 +/- 7 pM.« less

Reassessment of the structural basis of the ascending arousal system

PubMed Central

Fuller, Patrick M.; Sherman, David; Pedersen, Nigel P.; Saper, Clifford B.; Lu, Jun

2011-01-01

The “ascending reticular activating system” theory proposed that neurons in the upper brainstem reticular formation projected to forebrain targets that promoted wakefulness. More recent formulations have emphasized that most neurons at the pontomesencepahlic junction that participate in these pathways are actually in monoaminergic and cholinergic cell groups. However, cell-specific lesions of these cell groups have never been able to reproduce the deep coma seen after acute paramedian midbrain lesions that transect ascending axons at the caudal midbrain level. To determine whether the cortical afferents from the thalamus or the basal forebrain were more important in maintaining arousal, we first place large cell-body specific lesions in these targets. Surprisingly, extensive thalamic lesions had little effect on EEG or behavioral measures of wakefulness or on c-Fos expression by cortical neurons during wakefulness. In contrast, animals with large basal forebrain lesions were behaviorally unresponsive, had a monotonous sub-1 Hz EEG, and little cortical c-Fos expression during continuous gentle handling. We then retrogradely labeled inputs to the basal forebrain from the upper brainstem, and found a substantial input from glutamatergic neurons in the parabrachial nucleus and adjacent pre-coeruleus area. Cell specific lesions of the parabrachial-precoeruleus complex produced behavioral unresponsiveness, a monotonous sub-1Hz cortical EEG, and loss of cortical c-Fos expression during gentle handling. These experiments indicate that in rats the reticulo-thalamo-cortical pathway may play a very limited role in behavioral or electrocortical arousal, while the projection from the parabrachial nucleus and precoeruleus region, relayed by the basal forebrain to the cerebral cortex, may be critical for this process. PMID:21280045

Methadone patients exhibit increased startle and cortisol response after intravenous yohimbine.

PubMed

Stine, S M; Grillon, C G; Morgan, C A; Kosten, T R; Charney, D S; Krystal, J H

2001-03-01

Brain noradrenergic systems have been shown to be altered in opioid dependence and to mediate aspects of opioid withdrawal. Pre-clinical and clinical studies by others have shown that yohimbine, which increases noradrenergic activity, also increases both baseline and fear enhancement of the magnitude of the acoustic startle response (ASR). In a separate report from this experiment, it was shown that yohimbine produced opioid withdrawal-like symptoms, including anxiety, in clinically stable methadone-maintained patients and also produced elevations in the norepinepherine (NE) metabolite, 3-methoxy-4 hydroxyphenethyleneglycol (MHPG), and cortisol serum levels. The current study reports the effects of intravenous yohimbine hydrochloride, 0.4 mg/kg versus saline (double-blind), on ASR magnitude, plasma MHPG, and cortisol levels in eight methadone-maintained patients and 13 healthy subjects in a double-blind fashion. Yohimbine increased startle magnitude in both groups. There was no basal (placebo day) difference between the startle response of the two groups, but methadone patients had a larger startle magnitude increase in response to yohimbine than healthy controls. Methadone-maintained patients had lower baseline plasma levels of MHPG and similar baseline plasma cortisol levels compared with normal subjects. Yohimbine caused significant elevation in cortisol and MHPG in both groups. Methadone-maintained subjects had higher elevations in cortisol levels and MHPG (methadone main effect) levels in response to yohimbine. However, when MHPG levels were corrected for baseline differences by analysis of covariance (ANCOVA), the yohimbine effect, but not the methadone effect remained statistically significant. These results are consistent with the previous report and support the hypothesis that abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis and of noradrenergic mechanisms of stress response persist in opioid-agonist maintenance. The ASR effect extends the previous report and provides an additional objective measure for perturbation of noradrenergic and stress responses in these patients.

Readability Levels of First and Second Grade Basal Texts.

ERIC Educational Resources Information Center

Langan, Yvette

The Fry Readability Formula was used to determine the readability levels of 12 first and second grade basal texts. These texts were part of the Ginn 360, Ginn 720, and Macmillan Series "r" basal reader series. The results showed that 4 of the 12 books tested did not correspond closely to the publisher's readability levels. The Ginn 720 text for…

[Functional morphology of the submandibular salivary glands of white rats during aging involution].

PubMed

Rybakova, M G

1979-12-01

Functional morphology of different zones of submandibular glands of albino rats was studied quantitatively with due regard for the stages of neuroendocrine system involution. It is shown that function of salivary glands during ageing is not altered; cyclic fluctuations with estral cycle phases are maintained similarly to those in young animals. But the basal level of proteins and mucopolysaccharides is reduced, their mean levels being equal to the minimal level in young animals. On the other hand, activation of enzymes responsible for energy and transport processes takes place and their relationships change. The data obtained prove the relationship between salivary and endocrine glands and confirm the viewpoint that in early age involution disintegration occurs between different parameters of the functional activity of salivary glands rather than there take place changes in their function.

Cold basal conditions during surges control flow of fringing Arctic ice caps in Greenland

NASA Astrophysics Data System (ADS)

Cook, Samuel; Christoffersen, Poul; Todd, Joe; Palmer, Steven

2017-04-01

Fringing ice caps separated from larger ice sheets are rarely studied, yet they are an important part of earth's cryosphere, which has become the largest source of global sea-level rise. Understanding marginal ice caps is crucial for being able to predict sea-level change as they are responsible for up to 20% of Greenland's mass loss for 2003-2008. Studies of fringing ice caps can furthermore provide useful insights into processes operating on glaciers that surge. Surging has been the focus of much recent glaciological work, especially with reference to thermal evolution of polythermal glaciers in High Mountain Asia and the High Arctic. This has shown that the classic divide between hydrologically-controlled surges ('hard-bed') in Alaska and thermally-regulated ('soft-bed') surges elsewhere is less stark than previously assumed. Studying marginal ice caps can therefore be valuable in several ways. The largest fringing ice cap in Greenland is Flade Isblink. Previous work has established that this ice cap is showing a range of dynamic behaviour, including subglacial lake drainage and varied patterns of mass-balance change. In particular, a substantial surge, assumed to be caused by a version of the thermally-regulated mechanism, occurred between 1996 and 2000, making the ice cap a useful case study for investigating this process. Here we investigate the surge on Flade Isblink using the open-source, Full-Stokes model Elmer/Ice to invert for basal conditions and englacial temperatures using the adjoint method. We specifically study steady-state conditions representative of the active surge phase in 2000, and the subsequent quiescent phase, using patterns of surface velocity observed in 2000, 2005, 2008 and 2015. Under constant geometry, temperature and geothermal heat, it is shown that surging increases basal freezing rates by over 60% across an area that is twice as large as the area over which the bed freezes in the quiescent phase. The process responsible for this is the conductive heat loss, which increases faster than frictional heat is produced. When the bed becomes weaker, basal conditions become colder despite faster basal sliding, resulting in steep basal ice temperature gradients, which transfer heat effectively from the bed into the ice. In contrast, we find the increase in frictional heat to be insufficient, because weaker basal conditions offset the effect of faster basal sliding. Hence, frictional heat cannot provide enough extra melting to maintain surge conditions. We hypothesise that this heat transfer mechanism terminates surges on Flade Isblink, irrespective of any thinning that would also occur. The latter is not included in our model, but is required in the classic soft-bed surge model. In the quiescent phase, lower temperature gradients reduce the conductive heat loss, while a stronger bed produces more frictional heat, favouring basal melting and a warm bed, which ultimately create the weak basal conditions that result in yet another surge, regardless of any change in ice thickness. Our results indicate that soft-bed surges may occur even if the surge-related change in glacier geometry is modest, making surging glaciers of this type similar to ice streams that stagnate and reactivate periodically.

Comparison of serum triglyceride levels with propofol in long chain triglyceride and propofol in medium and long chain triglyceride after short term anesthesia in pediatric patients.

PubMed

Bhukal, Ishwar; Thimmarayan, Gokul; Bala, Indu; Solanki, Sohan Lal; Samra, Tanvir

2014-11-01

Significant increase in serum triglyceride (ST) concentration have been described in adult population after prolonged administration of propofol formulation containing long chain triglyceride (LCT). Though, medium chain triglyceride-LCT (MCT-LCT) propofol when compared with LCT propofol for long-term sedation in adults resulted in identical triglyceride levels, the elimination of triglyceride was faster in patients administered MCT-LCT propofol. A total of 40 children were randomized into two groups of 20 each; Group I were induced with 1% LCT propofol (3 mg/kg) and Group II with 1% medium and LCT propofol and maintained with descalating dose of 20.15 and 10 mg/kg/h at 10 min intervals. Blood samples for ST concentration were obtained before induction of anesthesia, at the end of propofol infusion and 4 h after terminating propofol infusion. ST levels were raised significantly above the basal values in both the groups but the rise was significantly higher in Group I (P < 0.05). Four hours after stopping propofol infusion the triglyceride levels were similar to the basal values in Group II, whereas in Group I the values were significantly greater than the baseline (P < 0.05) as well as those of Group II (P < 0.05). No clinically significant adverse effect of hypertriglyceridemia was observed. Even short term anesthesia with LCT and MCT-LCT propofol (1%) leads to elevated ST levels. The increase in ST levels is less with MCT-LCT propofol and elimination of triglyceride is also rapid after terminating MCT-LCT propofol infusion.

Niche induced cell death and epithelial phagocytosis regulate hair follicle stem cell pool

PubMed Central

Mesa, Kailin R.; Rompolas, Panteleimon; Zito, Giovanni; Myung, Peggy; Sun, Thomas Yang; Brown, Samara; Gonzalez, David; Blagoev, Krastan B.; Haberman, Ann M.; Greco, Valentina

2015-01-01

Summary Tissue homeostasis is achieved through a balance of cell production (growth) and elimination (regression)1,2. Contrary to tissue growth, the cells and molecular signals required for tissue regression remain unknown. To investigate physiological tissue regression, we use the mouse hair follicle, which cycles stereotypically between phases of growth and regression while maintaining a pool of stem cells to perpetuate tissue regeneration3. Here we show by intravital microscopy in live mice4–6 that the regression phase eliminates the majority of the epithelial cells by two distinct mechanisms: terminal differentiation of suprabasal cells and a spatial gradient of apoptosis of basal cells. Furthermore, we demonstrate that basal epithelial cells collectively act as phagocytes to clear dying epithelial neighbors. Through cellular and genetic ablation we show that epithelial cell death is extrinsically induced through TGFβ activation and mesenchymal crosstalk. Strikingly, our data show that regression acts to reduce the stem cell pool as inhibition of regression results in excess basal epithelial cells with regenerative abilities. This study identifies the cellular behaviors and molecular mechanisms of regression that counterbalance growth to maintain tissue homeostasis. PMID:25849774

Regulation of expression of collagenase-3 in normal, differentiating rat osteoblasts

NASA Technical Reports Server (NTRS)

Winchester, S. K.; Bloch, S. R.; Fiacco, G. J.; Partridge, N. C.

1999-01-01

We investigated the regulation of collagenase-3 expression in normal, differentiating rat osteoblasts. Fetal rat calvarial cell cultures showed an increase in alkaline phosphatase activity reaching maximal levels between 7-14 days post-confluence, then declining with the onset of mineralization. Collagenase-3 mRNA was just detectable after proliferation ceased at day 7, increased up to day 21, and declined at later ages. Postconfluent cells maintained in non-mineralizing medium expressed collagenase-3 but did not show the developmental increase exhibited by cells switched to mineralization medium. Cells maintained in non-mineralizing medium continued to proliferate; cells in mineralization medium ceased proliferation. In addition, collagenase-3 mRNA was not detected in subcultured cells allowed to remineralize. These results suggest that enhanced accumulation of collagenase-3 mRNA is triggered by cessation of proliferation or acquisition of a mineralized extracellular matrix and that other factors may also be required. After initiation of basal expression, parathyroid hormone (PTH) caused a dose-dependent increase in collagenase-3 mRNA. Both the cyclic adenosine monophosphate (cAMP) analogue, 8-bromo-cAMP (8-Br-cAMP), and the protein kinase C (PKC) activator, phorbol myristate acetate, increased collagenase-3 expression, while the calcium ionophore, ionomycin, did not, suggesting that PTH was acting through the protein kinase A (PKA) and PKC pathways. Inhibition of protein synthesis with cycloheximide caused an increase in basal collagenase-3 expression but blocked the effect of PTH, suggesting that an inhibitory factor prevents basal expression while an inductive factor is involved with PTH action. In summary, collagenase-3 is expressed in mineralized osteoblasts and cessation of proliferation and initiation of mineralization are triggers for collagenase-3 expression. PTH also stimulates expression of the enzyme through both PKA and PKC pathways in the mineralizing osteoblast. Copyright 1999 Wiley-Liss, Inc.

Use of a Novel Cell Adhesion Method and Digital Measurement to Show Stimulus-dependent Variation in Somatic and Oral Ciliary Beat Frequency in Paramecium

PubMed Central

Bell, Wade E.; Hallworth, Richard; Wyatt, Todd A.; Sisson, Joseph H.

2015-01-01

When Paramecium encounters positive stimuli, the membrane hyperpolarizes and ciliary beat frequency increases. We adapted an established immobilization protocol using a biological adhesive and a novel digital analysis system to quantify beat frequency in immobilized Paramecium. Cells showed low mortality and demonstrated beat frequencies consistent with previous studies. Chemoattractant molecules, reduction in external potassium, and posterior stimulation all increased somatic beat frequency. In all cases, the oral groove cilia maintained a higher beat frequency than mid-body cilia, but only oral cilia from cells stimulated with chemoattactants showed an increase from basal levels. PMID:25066640

Altered expression of prohibitin in psoriatic lesions and its cellular implication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Soon Young; Kim, Younghwa; Hwang, Ha Young

2007-08-31

Psoriasis is characterized by excessive proliferation of keratinocytes accompanying acanthosis and incomplete differentiation. Prohibitin was investigated by examining its function of HaCaT as well as psoriasis. Psoriatic involved skin revealed high level of prohibitin in the basal layer. Prohibitin was analyzed by applying RNAi (PHBi) with HaCaT, which demonstrated increased S-phase. PHBi showed enhanced sensitivity to anthralin-mediated cell death due to enhanced loss of mitochondrial membrane potential, suggesting a protective role of prohibitin against apoptosis. Collectively, prohibitin plays a role both in cell cycle regulation and in maintaining mitochondrial integrity, implying its association with pathogenesis of psoriasis.

Basal cortisol levels and metabolic syndrome: A systematic review and meta-analysis of observational studies.

PubMed

Garcez, Anderson; Leite, Heloísa Marquardt; Weiderpass, Elisabete; Paniz, Vera Maria Vieira; Watte, Guilherme; Canuto, Raquel; Olinto, Maria Teresa Anselmo

2018-05-17

To perform a qualitative synthesis (systematic review) and quantitative analysis (meta-analysis) to summarize the evidence regarding the relationship between basal cortisol levels and metabolic syndrome (MetS) in adults. A systematic search was performed in the PubMed, Embase, and PsycINFO databases for observational studies on the association between basal cortisol levels and MetS. The quality of individual studies was assessed by the Newcastle-Ottawa score. A random effects model was used to report pooled quantitative results and the I 2 statistic was used to assess heterogeneity. Egger's and Begg's tests were used to evaluate publication bias. Twenty-six studies (19 cross-sectional and seven case-control) met the inclusion criteria for the systematic review. The majority was classified as having a low risk of bias and used established criteria for the diagnosis of MetS. Twenty-one studies provided data on basal cortisol levels as continuous values and were included in the meta-analysis; they comprised 35 analyses and 11,808 subjects. Pooled results showed no significant difference in basal cortisol levels between subjects with and without MetS (standardized mean difference [SMD] = 0.02, 95% confidence interval [CI]=-0.11 to 0.14). There was high heterogeneity between the studies when all comparisons were considered (I 2  = 83.1%;p < 0.001). Paradoxically, meta-analysis of studies evaluating saliva samples showed no significantly lower basal cortisol levels among subjects with MetS (SMD=-0.18, 95% CI=-0.37 to 0.01), whereas those studies that evaluated serum samples (SMD = 0.11, 95% CI=-0.02 to 0.24) and urine samples (SMD = 0.73, 95% CI=-0.40 to 1.86) showed no significantly higher basal cortisol levels among subjects with MetS. In the subgroup and meta-regression analyses, a significant difference in basal cortisol levels was observed according to study design, population base, age, gender, cortisol level assessment method, and study quality. This systematic review and meta-analysis does not reveal any association between basal cortisol levels and MetS based on results of observational studies. The results of a random-effect meta-analysis showed no significant difference in basal cortisol levels between subjects with and without MetS. The present findings should be considered in order to help future studies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Association of basal serum androgen levels with ovarian response and ICSI cycle outcome.

PubMed

Abide Yayla, C; Ozkaya, E; Kayatas Eser, S; Sanverdi, I; Devranoglu, B; Kutlu, T

2018-05-01

The purpose of this study was to assess the predictive value of basal serum testosterone (T) and dehydroepiandrosterone sulfate (DHEAS) levels during follicular phase for ovarian response and outcome in intracytoplasmic sperm injection (ICSI) cycles of women with diminished ovarian reserve. We prospectively gathered data of basal serum androgen levels and ICSI cycle characteristics of 120 women with diminished ovarian reserve. Association of basal serum T and DHEAS levels with ovarian response was analyzed. Basal T and DHEAS levels were similar between pregnant and non-pregnant cases (P > 0.05). There were significant differences between groups with and without successful embryo implantation in terms of serum follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), gonadotropin starting and total dose, and peak estradiol level (P < 0.05). There were 58 (49.2%) cases who did not reach to the embryo transfer stage due to several reasons including cancelation of stimulation due to unresponsiveness (n = 26, 21.7%), no oocyte at oocyte pickup (n = 11, 9.2%), no mature oocyte (n = 6, 5%), and failure of fertilization or embryo development (n = 15, 12.5%). Basal androgen levels were not significant predictors for any of the cycle outcome. AMH level was a significant predictor for failure of fertilization or embryo development (AUC 0.722, P = 0.01) and cancelation of stimulation (AUC 0.801, P < 0.001). FSH was a significant predictor for cancelation of stimulation (AUC 0.774, P < 0.001). In women with diminished ovarian reserve, basal T and DHEAS levels have no value in predicting any of the cycle outcome parameters.

A time- and matrix-dependent TGFBR3–JUND–KRT5 regulatory circuit in single breast epithelial cells and basal-like premalignancies

PubMed Central

Wang, Chun-Chao; Bajikar, Sameer S.; Jamal, Leen; Atkins, Kristen A.; Janes, Kevin A.

2014-01-01

Basal-like breast carcinoma is characterized by poor prognosis and high intratumor heterogeneity. In an immortalized basal-like breast epithelial cell line, we identified two anti-correlated gene-expression programs that arise among single extracellular matrix (ECM)-attached cells during organotypic 3D culture. The first contains multiple TGFβ-related genes including TGFBR3, whereas the second contains JUND and the basal-like marker, KRT5. TGFBR3 and JUND interconnect through four negative-feedback loops to form a circuit that exhibits spontaneous damped oscillations in 3D culture. The TGFBR3–JUND circuit appears conserved in some premalignant lesions that heterogeneously express KRT5. The circuit depends on ECM engagement, as detachment causes a rewiring that is triggered by RPS6 dephosphorylation and maintained by juxtacrine tenascin C, which is critical for intraductal colonization of basal-like breast cancer cells in vivo. Intratumor heterogeneity need not stem from partial differentiation and could instead reflect dynamic toggling of cells between expression states that are not cell autonomous. PMID:24658685

Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number.

PubMed

Lyons, Jonathan J; Yu, Xiaomin; Hughes, Jason D; Le, Quang T; Jamil, Ali; Bai, Yun; Ho, Nancy; Zhao, Ming; Liu, Yihui; O'Connell, Michael P; Trivedi, Neil N; Nelson, Celeste; DiMaggio, Thomas; Jones, Nina; Matthews, Helen; Lewis, Katie L; Oler, Andrew J; Carlson, Ryan J; Arkwright, Peter D; Hong, Celine; Agama, Sherene; Wilson, Todd M; Tucker, Sofie; Zhang, Yu; McElwee, Joshua J; Pao, Maryland; Glover, Sarah C; Rothenberg, Marc E; Hohman, Robert J; Stone, Kelly D; Caughey, George H; Heller, Theo; Metcalfe, Dean D; Biesecker, Leslie G; Schwartz, Lawrence B; Milner, Joshua D

2016-12-01

Elevated basal serum tryptase levels are present in 4-6% of the general population, but the cause and relevance of such increases are unknown. Previously, we described subjects with dominantly inherited elevated basal serum tryptase levels associated with multisystem complaints including cutaneous flushing and pruritus, dysautonomia, functional gastrointestinal symptoms, chronic pain, and connective tissue abnormalities, including joint hypermobility. Here we report the identification of germline duplications and triplications in the TPSAB1 gene encoding α-tryptase that segregate with inherited increases in basal serum tryptase levels in 35 families presenting with associated multisystem complaints. Individuals harboring alleles encoding three copies of α-tryptase had higher basal serum levels of tryptase and were more symptomatic than those with alleles encoding two copies, suggesting a gene-dose effect. Further, we found in two additional cohorts (172 individuals) that elevated basal serum tryptase levels were exclusively associated with duplication of α-tryptase-encoding sequence in TPSAB1, and affected individuals reported symptom complexes seen in our initial familial cohort. Thus, our findings link duplications in TPSAB1 with irritable bowel syndrome, cutaneous complaints, connective tissue abnormalities, and dysautonomia.

Ski co-repressor complexes maintain the basal repressed state of the TGF-beta target gene, SMAD7, via HDAC3 and PRMT5.

PubMed

Tabata, Takanori; Kokura, Kenji; Ten Dijke, Peter; Ishii, Shunsuke

2009-01-01

The products encoded by ski and its related gene, sno, (Ski and Sno) act as transcriptional co-repressors and interact with other co-repressors such as N-CoR/SMRT and mSin3A. Ski and Sno mediate transcriptional repression by various repressors, including Mad, Rb and Gli3. Ski/Sno also suppress transcription induced by multiple activators, such as Smads and c-Myb. In particular, the inhibition of TGF-beta-induced transcription by binding to Smads is correlated with the oncogenic activity of Ski and Sno. However, the molecular mechanism by which Ski and Sno mediate transcriptional repression remains unknown. In this study, we report the purification and characterization of Ski complexes. The Ski complexes purified from HeLa cells contained histone deacetylase 3 (HDAC3) and protein arginine methyltransferase 5 (PRMT5), in addition to multiple Smad proteins (Smad2, Smad3 and Smad4). Chromatin immunoprecipitation assays indicated that these components of the Ski complexes were localized on the SMAD7 gene promoter, which is the TGF-beta target gene, in TGF-beta-untreated HepG2 cells. Knockdown of these components using siRNA led to up-regulation of SMAD7 mRNA. These results indicate that Ski complexes serve to maintain a TGF-beta-responsive promoter at a repressed basal level via the activities of histone deacetylase and histone arginine methyltransferase.

Role of calcium in phosphoinositide metabolism and inhibition of norepinephrine transport into synaptic vesicles by amphetamine analogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Knepper, S.M.

1985-01-01

Norepinephrine-(NE) and calcium ionophore A23187-stimulated phosphoinositide (PIn) metabolism in rat brain slices was studied under varying calcium conditions. Tissue was labelled with /sup 3/H-myo-inositol and /sup 3/H-inositol phosphates (IPn), products of PIn metabolism were measured. In the absence of media calcium the response to NE was decreased while that to A23187 was little affected A23187 can release calcium from intracellular stores. Basal and stimulated accumulation of /sup 3/H-IPn was reversibly antagonized with EGTA by addition of calcium. Using calcium buffers, approximately 10/sup -7/ M free calcium was required to support hydrolysis. Free intracellular calcium is maintained at approximately this level.more » Thus calcium is required for PIn hydrolysis but appears to play a permissive role, basal levels being sufficient to support metabolism. Conformationally-defined (rigid) and -restricted (semi-rigid) analogs of the most stable conformations of amphetamine, antiperiplanar (exo) and gauche (endo), were utilized to probe the conformational requirements of vesicular NE transport. Analogs tested were 2-aminotetralin (2AT), 3-methyltetrahydroisoquinoline, anti- and syn-9-aminobenzobicyclo(2.2.1)heptene, and endo and exo conformers of 2-aminobenzobicyclo(2.2.1)heptene and 2-aminobenzobicyclo(2.2.2)octene.« less

Vidarabine, an Anti-Herpes Virus Agent, Protects Against the Development of Heart Failure With Relatively Mild Side-Effects on Cardiac Function in a Canine Model of Pacing-Induced Dilated Cardiomyopathy.

PubMed

Nakamura, Takashi; Fujita, Takayuki; Kishimura, Megumi; Suita, Kenji; Hidaka, Yuko; Cai, Wenqian; Umemura, Masanari; Yokoyama, Utako; Uechi, Masami; Ishikawa, Yoshihiro

2016-11-25

In heart failure patients, chronic hyperactivation of sympathetic signaling is known to exacerbate cardiac dysfunction. In this study, the cardioprotective effect of vidarabine, an anti-herpes virus agent, which we identified as a cardiac adenylyl cyclase inhibitor, in dogs with pacing-induced dilated cardiomyopathy (DCM) was evaluated. In addition, the adverse effects of vidarabine on basal cardiac function was compared to those of the β-blocker, carvedilol.Methods and Results:Vidarabine and carvedilol attenuated the development of pacing-induced systolic dysfunction significantly and with equal effectiveness. Both agents also inhibited the development of cardiac apoptosis and fibrosis and reduced the Na + -Ca 2+ exchanger-1 protein level in the heart. Importantly, carvedilol significantly enlarged the left ventricle and atrium; vidarabine, in contrast, did not. Vidarabine-treated dogs maintained cardiac response to β-AR stimulation better than carvedilol-treated dogs did. Vidarabine may protect against pacing-induced DCM with less suppression of basal cardiac function than carvedilol in a dog model. (Circ J 2016; 80: 2496-2505).

Systemic production of IFN-alpha by garlic (Allium sativum) in humans.

PubMed

Bhattacharyya, Mau; Girish, G V; Karmohapatra, Soumendra K; Samad, S A; Sinha, Asru K

2007-05-01

The effect of foods on the production of interferon-alpha (IFN-alpha) is currently unknown. Garlic (Allium sativum) used as a folk medicine is reported to stimulate nitric oxide (NO) production. We investigated the systemic increase of NO due to the ingestion of garlic on the plasma IFN-alpha level in normal volunteers. Normal volunteers (10 groups, 10 in each group) ate 2 g fresh garlic, and plasma NO and IFN-alpha levels were determined after 2 and 4 h. The participants were also asked to eat garlic for various periods of time, and plasma NO and IFN-alpha were similarly assayed. Ingestion of 2 g fresh, but not boiled, garlic was found to increase the basal plasma level of NO from 2.7 +/- 0.1 microM to 8.76 +/- 0.21 microM at 2 and 4 h, respectively. The basal plasma IFN-alpha level increased from 9.51 +/- 0.26 nM to 46.3 +/- 1.2 nM in normal volunteers (n = 10) at the same time. The chronic eating of garlic was found to maintain IFN-alpha at high levels for at least 7 days. The exposure of neutrophils to garlic in vivo or in vitro, which also stimulated synthesis of NO in these cells, was found to stimulate IFN-alpha synthesis as measured by the stimulation of IFN-alpha mRNA synthesis. Thus, consumption of garlic resulted in stimulated synthesis of NO and, in turn, IFN-alpha in humans, which could be beneficial in viral or proliferative diseases.

NFE2-Related Transcription Factor 2 Coordinates Antioxidant Defense with Thyroglobulin Production and Iodination in the Thyroid Gland.

PubMed

Ziros, Panos G; Habeos, Ioannis G; Chartoumpekis, Dionysios V; Ntalampyra, Eleni; Somm, Emmanuel; Renaud, Cédric O; Bongiovanni, Massimo; Trougakos, Ioannis P; Yamamoto, Masayuki; Kensler, Thomas W; Santisteban, Pilar; Carrasco, Nancy; Ris-Stalpers, Carrie; Amendola, Elena; Liao, Xiao-Hui; Rossich, Luciano; Thomasz, Lisa; Juvenal, Guillermo J; Refetoff, Samuel; Sykiotis, Gerasimos P

2018-06-01

The thyroid gland has a special relationship with oxidative stress. While generation of oxidative substances is part of normal iodide metabolism during thyroid hormone synthesis, the gland must also defend itself against excessive oxidation in order to maintain normal function. Antioxidant and detoxification enzymes aid thyroid cells to maintain homeostasis by ameliorating oxidative insults, including during exposure to excess iodide, but the factors that coordinate their expression with the cellular redox status are not known. The antioxidant response system comprising the ubiquitously expressed NFE2-related transcription factor 2 (Nrf2) and its redox-sensitive cytoplasmic inhibitor Kelch-like ECH-associated protein 1 (Keap1) defends tissues against oxidative stress, thereby protecting against pathologies that relate to DNA, protein, and/or lipid oxidative damage. Thus, it was hypothesized that Nrf2 should also have important roles in maintaining thyroid homeostasis. Ubiquitous and thyroid-specific male C57BL6J Nrf2 knockout (Nrf2-KO) mice were studied. Plasma and thyroids were harvested for evaluation of thyroid function tests by radioimmunoassays and of gene and protein expression by real-time polymerase chain reaction and immunoblotting, respectively. Nrf2-KO and Keap1-KO clones of the PCCL3 rat thyroid follicular cell line were generated using CRISPR/Cas9 technology and were used for gene and protein expression studies. Software-predicted Nrf2 binding sites on the thyroglobulin enhancer were validated by site-directed in vitro mutagenesis and chromatin immunoprecipitation. The study shows that Nrf2 mediates antioxidant transcriptional responses in thyroid cells and protects the thyroid from oxidation induced by iodide overload. Surprisingly, it was also found that Nrf2 has a dramatic impact on both the basal abundance and the thyrotropin-inducible intrathyroidal abundance of thyroglobulin (Tg), the precursor protein of thyroid hormones. This effect is mediated by cell-autonomous regulation of Tg gene expression by Nrf2 via its direct binding to two evolutionarily conserved antioxidant response elements in an upstream enhancer. Yet, despite upregulating Tg levels, Nrf2 limits Tg iodination both under basal conditions and in response to excess iodide. Nrf2 exerts pleiotropic roles in the thyroid gland to couple cell stress defense mechanisms to iodide metabolism and the thyroid hormone synthesis machinery, both under basal conditions and in response to excess iodide.

Cardiomyocyte Circadian Oscillations Are Cell-Autonomous, Amplified by β-Adrenergic Signaling, and Synchronized in Cardiac Ventricle Tissue

PubMed Central

Welsh, David K.

2016-01-01

Circadian clocks impact vital cardiac parameters such as blood pressure and heart rate, and adverse cardiac events such as myocardial infarction and sudden cardiac death. In mammals, the central circadian pacemaker, located in the suprachiasmatic nucleus of the hypothalamus, synchronizes cellular circadian clocks in the heart and many other tissues throughout the body. Cardiac ventricle explants maintain autonomous contractions and robust circadian oscillations of clock gene expression in culture. In the present study, we examined the relationship between intrinsic myocardial function and circadian rhythms in cultures from mouse heart. We cultured ventricular explants or dispersed cardiomyocytes from neonatal mice expressing a PER2::LUC bioluminescent reporter of circadian clock gene expression. We found that isoproterenol, a β-adrenoceptor agonist known to increase heart rate and contractility, also amplifies PER2 circadian rhythms in ventricular explants. We found robust, cell-autonomous PER2 circadian rhythms in dispersed cardiomyocytes. Single-cell rhythms were initially synchronized in ventricular explants but desynchronized in dispersed cells. In addition, we developed a method for long-term, simultaneous monitoring of clock gene expression, contraction rate, and basal intracellular Ca2+ level in cardiomyocytes using PER2::LUC in combination with GCaMP3, a genetically encoded fluorescent Ca2+ reporter. In contrast to robust PER2 circadian rhythms in cardiomyocytes, we detected no rhythms in contraction rate and only weak rhythms in basal Ca2+ level. In summary, we found that PER2 circadian rhythms of cardiomyocytes are cell-autonomous, amplified by adrenergic signaling, and synchronized by intercellular communication in ventricle explants, but we detected no robust circadian rhythms in contraction rate or basal Ca2+. PMID:27459195

Expression analysis of the speech-related genes FoxP1 and FoxP2 and their relation to singing behavior in two songbird species.

PubMed

Chen, Qianqian; Heston, Jonathan B; Burkett, Zachary D; White, Stephanie A

2013-10-01

Humans and songbirds are among the rare animal groups that exhibit socially learned vocalizations: speech and song, respectively. These vocal-learning capacities share a reliance on audition and cortico-basal ganglia circuitry, as well as neurogenetic mechanisms. Notably, the transcription factors Forkhead box proteins 1 and 2 (FoxP1, FoxP2) exhibit similar expression patterns in the cortex and basal ganglia of humans and the zebra finch species of songbird, among other brain regions. Mutations in either gene are associated with language disorders in humans. Experimental knock-down of FoxP2 in the basal ganglia song control region Area X during song development leads to imprecise copying of tutor songs. Moreover, FoxP2 levels decrease naturally within Area X when zebra finches sing. Here, we examined neural expression patterns of FoxP1 and FoxP2 mRNA in adult Bengalese finches, a songbird species whose songs exhibit greater sequence complexity and increased reliance on audition for maintaining their quality. We found that FoxP1 and FoxP2 expression in Bengalese finches is similar to that in zebra finches, including strong mRNA signals for both factors in multiple song control nuclei and enhancement of FoxP1 in these regions relative to surrounding brain tissue. As with zebra finches, when Bengalese finches sing, FoxP2 is behaviorally downregulated within basal ganglia Area X over a similar time course, and expression negatively correlates with the amount of singing. This study confirms that in multiple songbird species, FoxP1 expression highlights song control regions, and regulation of FoxP2 is associated with motor control of song.

Expression analysis of the speech-related genes FoxP1 and FoxP2 and their relation to singing behavior in two songbird species

PubMed Central

Chen, Qianqian; Heston, Jonathan B.; Burkett, Zachary D.; White, Stephanie A.

2013-01-01

SUMMARY Humans and songbirds are among the rare animal groups that exhibit socially learned vocalizations: speech and song, respectively. These vocal-learning capacities share a reliance on audition and cortico-basal ganglia circuitry, as well as neurogenetic mechanisms. Notably, the transcription factors Forkhead box proteins 1 and 2 (FoxP1, FoxP2) exhibit similar expression patterns in the cortex and basal ganglia of humans and the zebra finch species of songbird, among other brain regions. Mutations in either gene are associated with language disorders in humans. Experimental knock-down of FoxP2 in the basal ganglia song control region Area X during song development leads to imprecise copying of tutor songs. Moreover, FoxP2 levels decrease naturally within Area X when zebra finches sing. Here, we examined neural expression patterns of FoxP1 and FoxP2 mRNA in adult Bengalese finches, a songbird species whose songs exhibit greater sequence complexity and increased reliance on audition for maintaining their quality. We found that FoxP1 and FoxP2 expression in Bengalese finches is similar to that in zebra finches, including strong mRNA signals for both factors in multiple song control nuclei and enhancement of FoxP1 in these regions relative to surrounding brain tissue. As with zebra finches, when Bengalese finches sing, FoxP2 is behaviorally downregulated within basal ganglia Area X over a similar time course, and expression negatively correlates with the amount of singing. This study confirms that in multiple songbird species, FoxP1 expression highlights song control regions, and regulation of FoxP2 is associated with motor control of song. PMID:24006346

The core planar cell polarity gene, Vangl2, maintains apical-basal organisation of the corneal epithelium.

PubMed

Panzica, D Alessio; Findlay, Amy S; van Ladesteijn, Rianne; Collinson, J Martin

2017-08-17

The role of the core planar cell polarity (PCP) pathway protein, Vangl2, was investigated in the corneal epithelium of the mammalian eye, a paradigm anatomical model of planar cell migration. The gene was conditionally knocked out in vivo and knocked down by siRNA, followed by immunohistochemical, behavioural and morphological analysis of corneal epithelial cells. The primary defects observed in vivo were of apical-basal organisation of the corneal epithelium, with abnormal stratification throughout life, mislocalisation of the cell membrane protein, Scribble, to the basal side of cells, and partial loss of the epithelial basement membrane. Planar defects in migration after wounding and in the presence of an applied electric field were noted. However, knockdown of Vangl2 also retarded cell migration in individual cells that had no contact with their neighbours, which precluded a classic PCP mechanism. It is concluded that some of the planar polarity phenotypes in PCP mutants may arise from disruption of apical-basal polarity. © 2017 Anatomical Society.

Cyclin D2 in the basal process of neural progenitors is linked to non-equivalent cell fates

PubMed Central

Tsunekawa, Yuji; Britto, Joanne M; Takahashi, Masanori; Polleux, Franck; Tan, Seong-Seng; Osumi, Noriko

2012-01-01

Asymmetric cell division plays an indispensable role during corticogenesis for producing new neurons while maintaining a self-renewing pool of apical progenitors. The cellular and molecular determinants favouring asymmetric division are not completely understood. Here, we identify a novel mechanism for generating cellular asymmetry through the active transportation and local translation of Cyclin D2 mRNA in the basal process. This process is regulated by a unique cis-regulatory sequence found in the 3′ untranslated region (3′UTR) of the mRNA. Unequal inheritance of Cyclin D2 protein to the basally positioned daughter cell with the basal process confers renewal of the apical progenitor after asymmetric division. Conversely, depletion of Cyclin D2 in the apically positioned daughter cell results in terminal neuronal differentiation. We demonstrate that Cyclin D2 is also expressed in the developing human cortex within similar domains, thus indicating that its role as a fate determinant is ancient and conserved. PMID:22395070

Basal testosterone, leadership and dominance: A field study and meta-analysis.

PubMed

van der Meij, Leander; Schaveling, Jaap; van Vugt, Mark

2016-10-01

This article examines the role of basal testosterone as a potential biological marker of leadership and hierarchy in the workplace. First, we report the result of a study with a sample of male employees from different corporate organizations in the Netherlands (n=125). Results showed that employees with higher basal testosterone levels reported a more authoritarian leadership style, but this relationship was absent among those who currently held a real management position (i.e., they had at least one subordinate). Furthermore, basal testosterone levels were not different between managers and non-managers, and testosterone was not associated with various indicators of status and hierarchy such as number of subordinates, income, and position in the organizational hierarchy. In our meta-analysis (second study), we showed that basal testosterone levels were not associated with leadership in men nor in women (9 studies, n=1103). Taken together, our findings show that basal testosterone is not associated with having a leadership position in the corporate world or related to leadership styles in leaders. We suggest that basal testosterone could play a role in acquiring leadership positions through dominant and authoritarian behavior. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Insulin degludec and insulin aspart: novel insulins for the management of diabetes mellitus

PubMed Central

Atkin, Stephen; Javed, Zeeshan; Fulcher, Gregory

2015-01-01

Patients with type 2 diabetes mellitus require insulin as disease progresses to attain or maintain glycaemic targets. Basal insulin is commonly prescribed initially, alone or with one or more rapid-acting prandial insulin doses, to limit mealtime glucose excursions (a basal–bolus regimen). Both patients and physicians must balance the advantages of improved glycaemic control with the risk of hypoglycaemia and increasing regimen complexity. The rapid-acting insulin analogues (insulin aspart, insulin lispro and insulin glulisine) all have similar pharmacokinetic and pharmacodynamic characteristics and clinical efficacy/safety profiles. However, there are important differences in the pharmacokinetic and pharmacodynamic profiles of basal insulins (insulin glargine, insulin detemir and insulin degludec). Insulin degludec is an ultra-long-acting insulin analogue with a flat and stable glucose-lowering profile, a duration of action exceeding 30 h and less inter-patient variation in glucose-lowering effect than insulin glargine. In particular, the chemical properties of insulin degludec have allowed the development of a soluble co-formulation with prandial insulin aspart (insulin degludec/insulin aspart) that provides basal insulin coverage for at least 24 h with additional mealtime insulin for one or two meals depending on dose frequency. Pharmacokinetic and pharmacodynamic studies have shown that the distinct, long basal glucose-lowering action of insulin degludec and the prandial glucose-lowering effect of insulin aspart are maintained in the co-formulation. Evidence from pivotal phase III clinical trials indicates that insulin degludec/insulin aspart translate into sustained glycaemic control with less hypoglycaemia and the potential for a simpler insulin regimen with fewer daily injections. PMID:26568812

Primary cilia maintain corneal epithelial homeostasis by regulation of the Notch signaling pathway

PubMed Central

Grisanti, Laura; Revenkova, Ekaterina; Gordon, Ronald E.

2016-01-01

Primary cilia have been linked to signaling pathways involved in cell proliferation, cell motility and cell polarity. Defects in ciliary function result in developmental abnormalities and multiple ciliopathies. Patients affected by severe ciliopathies, such as Meckel syndrome, present several ocular surface disease conditions of unclear pathogenesis. Here, we show that primary cilia are predominantly present on basal cells of the mouse corneal epithelium (CE) throughout development and in the adult. Conditional ablation of cilia in the CE leads to an increase in proliferation and vertical migration of basal corneal epithelial cells (CECs). A consequent increase in cell density of suprabasal layers results in a thicker than normal CE. Surprisingly, in cilia-deficient CE, cilia-mediated signaling pathways, including Hh and Wnt pathways, were not affected but the intensity of Notch signaling was severely diminished. Although Notch1 and Notch2 receptors were expressed normally, nuclear Notch1 intracellular domain (N1ICD) expression was severely reduced. Postnatal development analysis revealed that in cilia-deficient CECs downregulation of the Notch pathway precedes cell proliferation defects. Thus, we have uncovered a function of the primary cilium in maintaining homeostasis of the CE by balancing proliferation and vertical migration of basal CECs through modulation of Notch signaling. PMID:27122169

BMP-driven NRF2 activation in esophageal basal cell differentiation and eosinophilic esophagitis

PubMed Central

Jiang, Ming; Ku, Wei-Yao; Zhou, Zhongren; Dellon, Evan S.; Falk, Gary W.; Nakagawa, Hiroshi; Wang, Mei-Lun; Liu, Kuancan; Wang, Jun; Katzka, David A.; Peters, Jeffrey H.; Lan, Xiaopeng; Que, Jianwen

2015-01-01

Tissue homeostasis requires balanced self-renewal and differentiation of stem/progenitor cells, especially in tissues that are constantly replenished like the esophagus. Disruption of this balance is associated with pathological conditions, including eosinophilic esophagitis (EoE), in which basal progenitor cells become hyperplastic upon proinflammatory stimulation. However, how basal cells respond to the inflammatory environment at the molecular level remains undetermined. We previously reported that the bone morphogenetic protein (BMP) signaling pathway is critical for epithelial morphogenesis in the embryonic esophagus. Here, we address how this pathway regulates tissue homeostasis and EoE development in the adult esophagus. BMP signaling was specifically activated in differentiated squamous epithelium, but not in basal progenitor cells, which express the BMP antagonist follistatin. Previous reports indicate that increased BMP activity promotes Barrett’s intestinal differentiation; however, in mice, basal progenitor cell–specific expression of constitutively active BMP promoted squamous differentiation. Moreover, BMP activation increased intracellular ROS levels, initiating an NRF2-mediated oxidative response during basal progenitor cell differentiation. In both a mouse EoE model and human biopsies, reduced squamous differentiation was associated with high levels of follistatin and disrupted BMP/NRF2 pathways. We therefore propose a model in which normal squamous differentiation of basal progenitor cells is mediated by BMP-driven NRF2 activation and basal cell hyperplasia is promoted by disruption of BMP signaling in EoE. PMID:25774506

Endocrinology and Pediatric Exercise Science-2016.

PubMed

Eliakim, Alon

2017-02-01

The Pediatric Exercise Science Year That Was section aims to highlight the most important (to the author's opinion) manuscripts that were published in 2016 in the field of endocrinology and pediatric exercise science. This year's selection includes studies showing that 1) Induction of T4 to T3 conversion by type 2 deiodinase following aerobic exercise in skeletal muscles was associated with concomitant increase in peroxisome proliferatoractivated receptor-γ coactivator-1α, and mitochondrial oxidative capacity and therefore plays an important mechanistic role in the muscle adaptation to exercise training. 2) Hypothyroidism in fetal and early postnatal life was associated with impaired spatial learning and memory and with reduced hippocampal brain-derived neurotrophic factor in male and female rat pups. Forced (treadmill) and voluntary (wheel) exercise alleviated all these biochemical and neuro-cognitive deficits. 3) The relationship between different exercise intensities and carbohydrate requirements to maintain euglycemia at basal insulin levels among adolescent and young adults with Type 1 diabetes are nonlinear but rather inverted- U with no exogenous glucose required to maintain stable glucose level at high-intensity exercise (80%). The implication of these studies to the pediatric population, their importance and the new research avenues that were opened by these studies is emphasized.

A comparison of preoperative and postoperative nutritional states of lung transplant recipients.

PubMed

Madill, J; Maurer, J R; de Hoyos, A

1993-08-01

Malnutrition is a documented problem in some types of endstage lung disease (ESLD). Recently, isolated lung transplants have successfully reversed the respiratory failure of patients suffering from ESLD. In this study, we compare the preoperative and postoperative nutritional states of lung transplant recipients using weight-to-height ratios, anthropometric measurements, subjective global assessment, and biochemical blood values. Patients with emphysema, cystic fibrosis, and other types of bronchiectasis, but not patients with pulmonary fibrosis or pulmonary hypertension, were malnourished preoperatively. All groups had normal biochemical profiles. Caloric intake of patients with cystic fibrosis and bronchiectasis was increased above predicted basal energy expenditure levels. By six months to one year postoperatively, all groups of malnourished patients had significantly improved their nutritional status. Emphysema patients improved nutrition by maintaining preoperative caloric intake levels--however, both cystic fibrosis and bronchiectasis patients were able to achieve the same goal with significantly decreased caloric intakes. We conclude that malnourished ESLD patients receiving isolated lung grafts are able to achieve normal nutrition within one year posttransplant. Since this occurs in all cases with a reduced, or at best maintained, caloric intake, more study is needed to elucidate the factors that contribute to ESLD malnutrition.

Thalamocortical integration of instrumental learning and performance and their disintegration in addiction.

PubMed

Balleine, Bernard W; Morris, Richard W; Leung, Beatrice K

2015-12-02

A recent focus of addiction research has been on the effect of drug exposure on the neural processes that mediate the acquisition and performance of goal-directed instrumental actions. Deficits in goal-directed control and a consequent dysregulation of habit learning processes have been described as resulting in compulsive drug seeking. Similarly, considerable research has focussed on the motivational and emotional changes that drugs produce and that result in changes in the incentive processes that modulate goal-directed performance. Although these areas have developed independently, we argue that the effects they described are likely not independent. Here we hypothesize that these changes result from a core deficit in the way the learning and performance factors that support goal-directed action are integrated at a neural level to maintain behavioural control. A dorsal basal ganglia stream mediating goal-directed learning and a ventral stream mediating various performance factors find several points of integration in the cortical basal ganglia system, most notably in the thalamocortical network linking basal ganglia output to a variety of cortical control centres. Recent research in humans and other animals is reviewed suggesting that learning and performance factors are integrated in a network centred on the mediodorsal thalamus and that disintegration in this network may provide the basis for a 'switch' from recreational to dysregulated drug seeking resulting in the well documented changes associated with addiction. Copyright © 2014 Elsevier B.V. All rights reserved.

Baseline and post-stress seasonal changes in immunocompetence and redox state maintenance in the fishing bat Myotis vivesi.

PubMed

Hernández-Arciga, Ulalume; Herrera M, L Gerardo; Ibáñez-Contreras, Alejandra; Miranda-Labra, Roxana U; Flores-Martínez, José Juan; Königsberg, Mina

2018-01-01

Little is known of how the stress response varies when animals confront seasonal life-history processes. Antioxidant defenses and damage caused by oxidative stress and their link with immunocompetence are powerful biomarkers to assess animal´s physiological stress response. The aim of this study was A) to determine redox state and variation in basal (pre-acute stress) immune function during summer, autumn and winter (spring was not assessed due to restrictions in collecting permit) in the fish-eating Myotis (Myotis vivesi; Chiroptera), and B) to determine the effect of acute stress on immunocompetence and redox state during each season. Acute stress was stimulated by restricting animal movement for 6 and 12 h. The magnitude of the cellular immune response was higher during winter whilst that of the humoral response was at its highest during summer. Humoral response increased after 6 h of movement restriction stress and returned to baseline levels after 12 h. Basal redox state was maintained throughout the year, with no significant changes in protein damage, and antioxidant activity was modulated mainly in relation to variation to environment cues, increasing during high temperatures and decreasing during windy nights. Antioxidant activity increased after the 6 h of stressful stimuli especially during summer and autumn, and to a lesser extent in early winter, but redox state did not vary. However, protein damage increased after 12 h of stress during summer. Prolonged stress when the bat is engaged in activities of high energy demand overcame its capacity to maintain homeostasis resulting in oxidative damage.

Baseline and post-stress seasonal changes in immunocompetence and redox state maintenance in the fishing bat Myotis vivesi

PubMed Central

Ibáñez-Contreras, Alejandra; Miranda-Labra, Roxana U.; Flores-Martínez, José Juan

2018-01-01

Little is known of how the stress response varies when animals confront seasonal life-history processes. Antioxidant defenses and damage caused by oxidative stress and their link with immunocompetence are powerful biomarkers to assess animal´s physiological stress response. The aim of this study was A) to determine redox state and variation in basal (pre-acute stress) immune function during summer, autumn and winter (spring was not assessed due to restrictions in collecting permit) in the fish-eating Myotis (Myotis vivesi; Chiroptera), and B) to determine the effect of acute stress on immunocompetence and redox state during each season. Acute stress was stimulated by restricting animal movement for 6 and 12 h. The magnitude of the cellular immune response was higher during winter whilst that of the humoral response was at its highest during summer. Humoral response increased after 6 h of movement restriction stress and returned to baseline levels after 12 h. Basal redox state was maintained throughout the year, with no significant changes in protein damage, and antioxidant activity was modulated mainly in relation to variation to environment cues, increasing during high temperatures and decreasing during windy nights. Antioxidant activity increased after the 6 h of stressful stimuli especially during summer and autumn, and to a lesser extent in early winter, but redox state did not vary. However, protein damage increased after 12 h of stress during summer. Prolonged stress when the bat is engaged in activities of high energy demand overcame its capacity to maintain homeostasis resulting in oxidative damage. PMID:29293551

Specificity protein 1 (Sp1) maintains basal epithelial expression of the miR-200 family: implications for epithelial-mesenchymal transition.

PubMed

Kolesnikoff, Natasha; Attema, Joanne L; Roslan, Suraya; Bert, Andrew G; Schwarz, Quenten P; Gregory, Philip A; Goodall, Gregory J

2014-04-18

Epithelial-mesenchymal transition (EMT) is required for the specification of tissues during embryonic development and is recapitulated during the metastatic progression of tumors. The miR-200 family plays a critical role in enforcing the epithelial state with their expression lost in cells undergoing EMT. EMT can be mediated by activation of the ZEB1 and ZEB2 (ZEB) transcription factors, which repress miR-200 expression via a self-reinforcing double negative feedback loop to promote the mesenchymal state. However, it remains unclear what factors drive and maintain epithelial-specific expression of miR-200 in the absence of EMT-inducing factors. Here, we show that the transcription factor Specificity Protein 1 (Sp1) binds to the miR-200b∼200a∼429 proximal promoter and activates miR-200 expression in epithelial cells. In mesenchymal cells, Sp1 expression is maintained, but its ability to activate the miR-200 promoter is perturbed by ZEB-mediated repression. Reduction of Sp1 expression caused changes in EMT-associated markers in epithelial cells. Furthermore, we observed co-expression of Sp1 and miR-200 during mouse embryonic development wherein miR-200 expression was only lost in regions with high ZEB expression. Together, these findings indicate that miR-200 family members require Sp1 to drive basal expression and to maintain an epithelial state.

Fetuin-A levels in hyperthyroidism.

PubMed

Pamuk, Bariş Onder; Yilmaz, Hamiyet; Topcuoglu, Tugba; Bilgir, Oktay; Çalan, Ozlem; Pamuk, Gulseren; Ertugrul, Derun Taner

2013-01-01

Fetuin-A is a protein secreted from the liver that inhibits arterial calcification deposition and can contribute to insulin resistance. Hyperthyroidism is also associated with insulin resistance. It is not known whether hyperthyroidism has an effect on fetuin-A levels. We measured fetuin-A levels and homeostasis model of assessment-insulin resistance before hyperthyroidism treatment was initiated and after euthyroidism was achieved. A total of 42 patients diagnosed with hyperthyroidism were enrolled in this study. Fetuin-A, insulin, high-sensitivity C-reactive protein, fasting blood glucose, free T3 (fT3), free T4 (fT4), and thyrotropin were measured before and after euthyroidism was established. Basal fasting blood glucose, high-sensitivity C-reactive protein, insulin, c-peptide, homeostasis model of assessment-insulin resistance, fT3, fT4 and fetuin-A levels were significantly decreased after euthyroidism was achieved (Table 1). Basal fasting blood glucose (r:0.407, p:0.008), high-sensitivity C-reactive protein (r:0.523, p<0.0001), insulin (r:0.479, p:0.001), homeostasis model of assessment-insulin resistance (r:0.541, p<0.0001), fT3 (r:0.492, p:0.001) and fT4 (r:0.473, p:0.002) were positively correlated with basal fetuin-A levels. Basal thyrotropin levels were significantly negatively correlated (r:-0.553, p<0.0001) with basal fetuin-A levels. Our findings suggest that hyperthyroidism influences fetuin-A levels.

Diagnostic accuracy of basal TSH determinations based on the intravenous TRH stimulation test: an evaluation of 2570 tests and comparison with the literature.

PubMed

Moncayo, Helga; Dapunt, Otto; Moncayo, Roy

2007-08-02

Basal TSH levels reflect the metabolic status of thyroid function, however the definition and interpretation of the basal levels of TSH is a matter of controversial debate. The aim of this study was to evaluate basal TSH levels in relation to the physiological response to i.v. TRH stimulation. A series of 2570 women attending a specialized endocrine unit were evaluated. A standardized i.v. TRH stimulation test was carried out by applying 200 mug of TRH. TSH levels were measured both in the basal and the 30 minute blood sample. The normal response to TRH stimulation had been previously determined to be an absolute value lying between 2.5 and 20 mIU/l. Both TSH values were analyzed by cross tabulation. In addition the results were compared to reference values taken from the literature. Basal TSH values were within the normal range (0.3 to 3.5 mIU/l) in 91,5% of cases, diminished in 3,8% and elevated in 4.7%. Based on the response to TRH, 82.4% were considered euthyroid, 3.3% were latent hyperthyroid, and 14.3% were latent hypothyroid. Combining the data on basal and stimulated TSH levels, latent hypothyroidism was found in the following proportions for different TSH levels: 5.4% for TSH < 2.0 mIU/l, 30.2% for TSH between 2.0 and 3.0 mIU/l, 65,5% for TSH between 3.0 and 3.50 mIU/l, 87.5% for TSH between 3.5 and 4.0 mIU/l, and 88.2% for TSH between 4 and 5 mIU/l. The use of an upper normal range for TSH of 2.5 mIU/l, as recommended in the literature, misclassified 7.7% of euthyroid cases. Our analysis strategy allows us to delineate the predictive value of basal TSH levels in relation to latent hypothyroidism. A grey area can be identified for values between 3.0 and 3.5 mIU/l.

The thiazide sensitive sodium chloride co-transporter NCC is modulated by site-specific ubiquitylation.

PubMed

Rosenbaek, Lena L; Rizzo, Federica; Wu, Qi; Rojas-Vega, Lorena; Gamba, Gerardo; MacAulay, Nanna; Staub, Olivier; Fenton, Robert A

2017-10-11

The renal sodium chloride cotransporter, NCC, in the distal convoluted tubule is important for maintaining body Na + and K + homeostasis. Endogenous NCC is highly ubiquitylated, but the role of individual ubiquitylation sites is not established. Here, we assessed the role of 10 ubiquitylation sites for NCC function. Transient transfections of HEK293 cells with human wildtype (WT) NCC or various K to R mutants identified greater membrane abundance for K706R, K828R and K909R mutants. Relative to WT-NCC, stable tetracycline inducible MDCKI cell lines expressing K706R, K828R and K909R mutants had significantly higher total and phosphorylated NCC levels at the apical plasma membrane under basal conditions. Low chloride stimulation increased membrane abundance of all mutants to similar or greater levels than WT-NCC. Under basal conditions K828R and K909R mutants had less ubiquitylated NCC in the plasma membrane, and all mutants displayed reduced NCC ubiquitylation following low chloride stimulation. Thiazide-sensitive sodium-22 uptakes were elevated in the mutants and internalization from the plasma membrane was significantly less than WT-NCC. K909R had increased half-life, whereas chloroquine or MG132 treatment indicated that K706 and K909 play roles in lysosomal and proteasomal NCC degradation, respectively. In conclusion, site-specific ubiquitylation of NCC plays alternative roles for NCC function.

Fossil evidence for key innovations in the evolution of insect diversity.

PubMed

Nicholson, David B; Ross, Andrew J; Mayhew, Peter J

2014-10-22

Explaining the taxonomic richness of the insects, comprising over half of all described species, is a major challenge in evolutionary biology. Previously, several evolutionary novelties (key innovations) have been posited to contribute to that richness, including the insect bauplan, wings, wing folding and complete metamorphosis, but evidence over their relative importance and modes of action is sparse and equivocal. Here, a new dataset on the first and last occurrences of fossil hexapod (insects and close relatives) families is used to show that basal families of winged insects (Palaeoptera, e.g. dragonflies) show higher origination and extinction rates in the fossil record than basal wingless groups (Apterygota, e.g. silverfish). Origination and extinction rates were maintained at levels similar to Palaeoptera in the more derived Polyneoptera (e.g. cockroaches) and Paraneoptera (e.g. true bugs), but extinction rates subsequently reduced in the very rich group of insects with complete metamorphosis (Holometabola, e.g. beetles). Holometabola show evidence of a recent slow-down in their high net diversification rate, whereas other winged taxa continue to diversify at constant but low rates. These data suggest that wings and complete metamorphosis have had the most effect on family-level insect macroevolution, and point to specific mechanisms by which they have influenced insect diversity through time. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Proinflammatory cytokines and response to molds in mononuclear cells of patients with Meniere disease.

PubMed

Frejo, Lidia; Gallego-Martinez, Alvaro; Requena, Teresa; Martin-Sanz, Eduardo; Amor-Dorado, Juan Carlos; Soto-Varela, Andres; Santos-Perez, Sofia; Espinosa-Sanchez, Juan Manuel; Batuecas-Caletrio, Angel; Aran, Ismael; Fraile, Jesus; Rossi-Izquierdo, Marcos; Lopez-Escamez, Jose Antonio

2018-04-13

Epidemiological studies have found a higher prevalence of allergic symptoms and positive prick tests in patients with Meniere's disease (MD); however the effect of allergenic extracts in MD has not been established. Thus, this study aims to determine the effect of Aspergillus and Penicillium stimulation in cytokine release and gene expression profile in MD. Patients with MD showed higher basal levels of IL-1β, IL-1RA, IL-6 and TNF-α when compared to healthy controls. We observed that IL-1β levels had a bimodal distribution suggesting two different subgroups of patients, with low and high basal levels of cytokines. Gene expression profile in peripheral blood mononuclear cells (PBMC) showed significant differences in patients with high and low basal levels of IL-1β. We found that both mold extracts triggered a significant release of TNF-α in MD patients, which were not found in controls. Moreover, after mold stimulation, MD patients showed a different gene expression profile in PBMC, according to the basal levels of IL-1β. The results indicate that a subset of MD patients have higher basal levels of proinflammatory cytokines and the exposure to Aspergillus and Penicillium extracts may trigger additional TNF-α release and contribute to exacerbate inflammation.

Intracochlear Position of Cochlear Implants Determined Using CT Scanning versus Fitting Levels: Higher Threshold Levels at Basal Turn.

PubMed

van der Beek, Feddo B; Briaire, Jeroen J; van der Marel, Kim S; Verbist, Berit M; Frijns, Johan H M

2016-01-01

In this study, the effects of the intracochlear position of cochlear implants on the clinical fitting levels were analyzed. A total of 130 adult subjects who used a CII/HiRes 90K cochlear implant with a HiFocus 1/1J electrode were included in the study. The insertion angle and the distance to the modiolus of each electrode contact were determined using high-resolution CT scanning. The threshold levels (T-levels) and maximum comfort levels (M-levels) at 1 year of follow-up were determined. The degree of speech perception of the subjects was evaluated during routine clinical follow-up. The depths of insertion of all the electrode contacts were determined. The distance to the modiolus was significantly smaller at the basal and apical cochlear parts compared with that at the middle of the cochlea (p < 0.05). The T-levels increased toward the basal end of the cochlea (3.4 dB). Additionally, the M-levels, which were fitted in our clinic using a standard profile, also increased toward the basal end, although with a lower amplitude (1.3 dB). Accordingly, the dynamic range decreased toward the basal end (2.1 dB). No correlation was found between the distance to the modiolus and the T-level or the M-level. Furthermore, the correlation between the insertion depth and stimulation levels was not affected by the duration of deafness, age at implantation or the time since implantation. Additionally, the T-levels showed a significant correlation with the speech perception scores (p < 0.05). The stimulation levels of the cochlear implants were affected by the intracochlear position of the electrode contacts, which were determined using postoperative CT scanning. Interestingly, these levels depended on the insertion depth, whereas the distance to the modiolus did not affect the stimulation levels. The T-levels increased toward the basal end of the cochlea. The level profiles were independent of the overall stimulation levels and were not affected by the biographical data of the patients, such as the duration of deafness, age at implantation or time since implantation. Further research is required to elucidate how fitting using level profiles with an increase toward the basal end of the cochlea benefits speech perception. Future investigations may elucidate an explanation for the effects of the intracochlear electrode position on the stimulation levels and might facilitate future improvements in electrode design. © 2016 S. Karger AG, Basel.

Protective effect of caspase inhibition on compression-induced muscle damage

PubMed Central

Teng, Bee T; Tam, Eric W; Benzie, Iris F; Siu, Parco M

2011-01-01

Abstract There are currently no effective therapies for treating pressure-induced deep tissue injury. This study tested the efficacy of pharmacological inhibition of caspase in preventing muscle damage following sustained moderate compression. Adult Sprague–Dawley rats were subjected to prolonged moderate compression. Static pressure of 100 mmHg compression was applied to an area of 1.5 cm2 in the tibialis region of the right limb of the rats for 6 h each day for two consecutive days. The left uncompressed limb served as intra-animal control. Rats were randomized to receive either vehicle (DMSO) as control treatment (n = 8) or 6 mg kg−1 of caspase inhibitor (z-VAD-fmk; n = 8) prior to the 6 h compression on the two consecutive days. Muscle tissues directly underneath the compression region of the compressed limb and the same region of control limb were harvested after the compression procedure. Histological examination and biochemical/molecular measurement of apoptosis and autophagy were performed. Caspase inhibition was effective in alleviating the compression-induced pathohistology of muscle. The increases in caspase-3 protease activity, TUNEL index, apoptotic DNA fragmentation and pro-apoptotic factors (Bax, p53 and EndoG) and the decreases in anti-apoptotic factors (XIAP and HSP70) observed in compressed muscle of DMSO-treated animals were not found in animals treated with caspase inhibitor. The mRNA content of autophagic factors (Beclin-1, Atg5 and Atg12) and the protein content of LC3, FoxO3 and phospho-FoxO3 that were down-regulated in compressed muscle of DMSO-treated animals were all maintained at their basal level in the caspase inhibitor treated animals. Our data provide evidence that caspase inhibition attenuates compression-induced muscle apoptosis and maintains the basal autophagy level. These findings demonstrate that pharmacological inhibition of caspase/apoptosis is effective in alleviating muscle damage as induced by prolonged compression. PMID:21540338

Serial hepatic gene expression profiling in Angus steers during feed restriction and realimentation

USDA-ARS?s Scientific Manuscript database

Growing ruminants maintained under dietary restriction for extended periods will exhibit compensatory growth when reverted to ad libitum feeding. This period of compensatory growth is associated with increased feed efficiency, lower basal energy requirements, and changes in circulating concentration...

Expansion of stem cells counteracts age-related mammary regression in compound Timp1/Timp3 null mice.

PubMed

Jackson, Hartland W; Waterhouse, Paul; Sinha, Ankit; Kislinger, Thomas; Berman, Hal K; Khokha, Rama

2015-03-01

Age is the primary risk factor for breast cancer in women. Bipotent basal stem cells actively maintain the adult mammary ductal tree, but with age tissues atrophy. We show that cell-extrinsic factors maintain the adult stem cell pool during ageing and dictate tissue stoichiometry. Mammary stem cells spontaneously expand more than 11-fold in virgin adult female mice lacking specific genes for TIMPs, the natural metalloproteinase inhibitors. Compound Timp1/Timp3 null glands exhibit Notch activation and accelerated gestational differentiation. Proteomics of mutant basal cells uncover altered cytoskeletal and extracellular protein repertoires, and we identify aberrant mitotic spindle orientation in these glands, a process that instructs asymmetric cell division and fate. We find that progenitor activity normally declines with age, but enriched stem/progenitor pools prevent tissue regression in Timp mutant mammary glands without affecting carcinogen-induced cancer susceptibility. Thus, improved stem cell content can extend mouse mammary tissue lifespan without altering cancer risk in this mouse model.

Drosophila larvae lacking the bcl-2 gene, buffy, are sensitive to nutrient stress, maintain increased basal target of rapamycin (Tor) signaling and exhibit characteristics of altered basal energy metabolism

PubMed Central

2012-01-01

Background B cell lymphoma 2 (Bcl-2) proteins are the central regulators of apoptosis. The two bcl-2 genes in Drosophila modulate the response to stress-induced cell death, but not developmental cell death. Because null mutants are viable, Drosophila provides an optimum model system to investigate alternate functions of Bcl-2 proteins. In this report, we explore the role of one bcl-2 gene in nutrient stress responses. Results We report that starvation of Drosophila larvae lacking the bcl-2 gene, buffy, decreases survival rate by more than twofold relative to wild-type larvae. The buffy null mutant reacted to starvation with the expected responses such as inhibition of target of rapamycin (Tor) signaling, autophagy initiation and mobilization of stored lipids. However, the autophagic response to starvation initiated faster in larvae lacking buffy and was inhibited by ectopic buffy. We demonstrate that unusually high basal Tor signaling, indicated by more phosphorylated S6K, was detected in the buffy mutant and that removal of a genomic copy of S6K, but not inactivation of Tor by rapamycin, reverted the precocious autophagy phenotype. Instead, Tor inactivation also required loss of a positive nutrient signal to trigger autophagy and loss of both was sufficient to activate autophagy in the buffy mutant even in the presence of enforced phosphoinositide 3-kinase (PI3K) signaling. Prior to starvation, the fed buffy mutant stored less lipid and glycogen, had high lactate levels and maintained a reduced pool of cellular ATP. These observations, together with the inability of buffy mutant larvae to adapt to nutrient restriction, indicate altered energy metabolism in the absence of buffy. Conclusions All animals in their natural habitats are faced with periods of reduced nutrient availability. This study demonstrates that buffy is required for adaptation to both starvation and nutrient restriction. Thus, Buffy is a Bcl-2 protein that plays an important non-apoptotic role to promote survival of the whole organism in a stressful situation. PMID:22824239

Basal C-peptide Level as a Surrogate Marker of Subclinical Atherosclerosis in Type 2 Diabetic Patients

PubMed Central

Kim, Sung-Tae; Kim, Byung-Joon; Song, In-Geol; Jung, Jang-Han; Lee, Kang-Woo; Park, Keun-Young; Cho, Youn-Zoo; Lee, Dae-Ho; Koh, Gwan-Pyo

2011-01-01

Background Recent studies have revealed that C-peptide induces smooth muscle cell proliferation and causes human atherosclerotic lesions in diabetic patients. The present study was designed to examine whether the basal C-peptide levels correlate with cardiovascular risk in type 2 diabetes mellitus (T2DM) patients. Methods Data was obtained from 467 patients with T2DM from two institutions who were followed for four years. The medical findings of all patients were reviewed, and patients with creatinine >1.4 mg/dL, any inflammation or infection, hepatitis, or type 1 DM were excluded. The relationships between basal C-peptide and other clinical values were statistically analyzed. Results A simple correlation was found between basal C-peptide and components of metabolic syndrome (MS). Statistically basal C-peptide levels were significantly higher than the three different MS criteria used in the present study, the Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program's (NCEP's), World Health Organization (WHO), and the International Diabetes Federation (IDF) criteria (NCEP-ATP III, P=0.001; IDF, P<0.001; WHO, P=0.029). The multiple regression analysis between intima-media thickness (IMT) and clinical values showed that basal C-peptide significantly correlated with IMT (P=0.043), while the analysis between the 10-year coronary heart disease risk by the United Kingdom Prospective Diabetes Study risk engine and clinical values showed that basal C-peptide did not correlate with IMT (P=0.226). Conclusion Basal C-peptide is related to cardiovascular predictors (IMT) of T2DM, suggesting that basal C-peptide does provide a further indication of cardiovascular disease. PMID:21537412

50 Hz hippocampal stimulation in refractory epilepsy: Higher level of basal glutamate predicts greater release of glutamate.

PubMed

Cavus, Idil; Widi, Gabriel A; Duckrow, Robert B; Zaveri, Hitten; Kennard, Jeremy T; Krystal, John; Spencer, Dennis D

2016-02-01

The effect of electrical stimulation on brain glutamate release in humans is unknown. Glutamate is elevated at baseline in the epileptogenic hippocampus of patients with refractory epilepsy, and increases during spontaneous seizures. We examined the effect of 50 Hz stimulation on glutamate release and its relationship to interictal levels in the hippocampus of patients with epilepsy. In addition, we measured basal and stimulated glutamate levels in a subset of these patients where stimulation elicited a seizure. Subjects (n = 10) were patients with medically refractory epilepsy who were undergoing intracranial electroencephalography (EEG) evaluation in an epilepsy monitoring unit. Electrical stimulation (50 Hz) was delivered through implanted hippocampal electrodes (n = 11), and microdialysate samples were collected every 2 min. Basal glutamate, changes in glutamate efflux with stimulation, and the relationships between peak stimulation-associated glutamate concentrations, basal zero-flow levels, and stimulated seizures were examined. Stimulation of epileptic hippocampi in patients with refractory epilepsy caused increases in glutamate efflux (p = 0.005, n = 10), and 4 of ten patients experienced brief stimulated seizures. Stimulation-induced increases in glutamate were not observed during the evoked seizures, but rather were related to the elevation in interictal basal glutamate (R(2) = 0.81, p = 0.001). The evoked-seizure group had lower basal glutamate levels than the no-seizure group (p = 0.04), with no stimulation-induced change in glutamate efflux (p = 0.47, n = 4). Conversely, increased glutamate was observed following stimulation in the no-seizure group (p = 0.005, n = 7). Subjects with an atrophic hippocampus had higher basal glutamate levels (p = 0.03, n = 7) and higher stimulation-induced glutamate efflux. Electrical stimulation of the epileptic hippocampus either increased extracellular glutamate efflux or induced seizures. The magnitude of stimulated glutamate increase was related to elevation in basal interictal glutamate, suggesting a common mechanism, possibly impaired glutamate metabolism. Divergent mechanisms may exist for seizure induction and increased glutamate in patients with epilepsy. These data highlight the potential risk of 50 Hz stimulation in patients with epilepsy. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Fetuin-A levels in hyperthyroidism

PubMed Central

Pamuk, Barış Onder; Yılmaz, Hamiyet; Topcuoglu, Tugba; Bilgir, Oktay; Çalan, Ozlem; Pamuk, Gulseren; Ertugrul, Derun Taner

2013-01-01

OBJECTIVE: Fetuin-A is a protein secreted from the liver that inhibits arterial calcification deposition and can contribute to insulin resistance. Hyperthyroidism is also associated with insulin resistance. It is not known whether hyperthyroidism has an effect on fetuin-A levels. METHODS: We measured fetuin-A levels and homeostasis model of assessment-insulin resistance before hyperthyroidism treatment was initiated and after euthyroidism was achieved. A total of 42 patients diagnosed with hyperthyroidism were enrolled in this study. Fetuin-A, insulin, high-sensitivity C-reactive protein, fasting blood glucose, free T3 (fT3), free T4 (fT4), and thyrotropin were measured before and after euthyroidism was established. RESULTS: Basal fasting blood glucose, high-sensitivity C-reactive protein, insulin, c-peptide, homeostasis model of assessment-insulin resistance, fT3, fT4 and fetuin-A levels were significantly decreased after euthyroidism was achieved (Table 1. Basal fasting blood glucose (r:0.407, p:0.008), high-sensitivity C-reactive protein (r:0.523, p<0.0001), insulin (r:0.479, p:0.001), homeostasis model of assessment-insulin resistance (r:0.541, p<0.0001), fT3 (r:0.492, p:0.001) and fT4 (r:0.473, p:0.002) were positively correlated with basal fetuin-A levels. Basal thyrotropin levels were significantly negatively correlated (r:-0.553, p<0.0001) with basal fetuin-A levels. CONCLUSION: Our findings suggest that hyperthyroidism influences fetuin-A levels. PMID:23644859

The cyclin-dependent kinase PITSLRE/CDK11 is required for successful autophagy.

PubMed

Wilkinson, Simon; Croft, Daniel R; O'Prey, Jim; Meedendorp, Arenda; O'Prey, Margaret; Dufès, Christine; Ryan, Kevin M

2011-11-01

(Macro)autophagy is a membrane-trafficking process that serves to sequester cellular constituents in organelles termed autophagosomes, which target their degradation in the lysosome. Autophagy operates at basal levels in all cells where it serves as a homeostatic mechanism to maintain cellular integrity. The levels and cargoes of autophagy can, however, change in response to a variety of stimuli, and perturbations in autophagy are known to be involved in the aetiology of various human diseases. Autophagy must therefore be tightly controlled. We report here that the Drosophila cyclin-dependent kinase PITSLRE is a modulator of autophagy. Loss of the human PITSLRE orthologue, CDK11, initially appears to induce autophagy, but at later time points CDK11 is critically required for autophagic flux and cargo digestion. Since PITSLRE/CDK11 regulates autophagy in both Drosophila and human cells, this kinase represents a novel phylogenetically conserved component of the autophagy machinery.

On the nature of the dirty ice at the bottom of the GISP2 ice core

USGS Publications Warehouse

Bender, Michael L.; Burgess, Edward; Alley, Richard B.; Barnett, Bruce; Clow, Gary D.

2010-01-01

We present data on the triple Ar isotope composition in trapped gas from clean, stratigraphically disturbed ice between 2800 and 3040m depth in the GISP2 ice core, and from basal dirty ice from 3040 to 3053m depth. We also present data for the abundance and isotopic composition of O2 and N2, and abundance of Ar, in the basal dirty ice. The Ar/N2 ratio of dirty basal ice, the heavy isotope enrichment (reflecting gravitational fractionation), and the total gas content all indicate that the gases in basal dirty ice originate from the assimilation of clean ice of the overlying glacier, which comprises most of the ice in the dirty bottom layer. O2 is partly to completely depleted in basal ice, reflecting active metabolism. The gravitationally corrected ratio of 40Ar/38Ar, which decreases with age in the global atmosphere, is compatible with an age of 100-250ka for clean disturbed ice. In basal ice, 40Ar is present in excess due to injection of radiogenic 40Ar produced in the underlying continental crust. The weak depth gradient of 40Ar in the dirty basal ice, and the distribution of dirt, indicate mixing within the basal ice, while various published lines of evidence indicate mixing within the overlying clean, disturbed ice. Excess CH4, which reaches thousands of ppm in basal dirty ice at GRIP, is virtually absent in overlying clean disturbed ice, demonstrating that mixing of dirty basal ice into the overlying clean ice, if it occurs at all, is very slow. Order-of-magnitude estimates indicate that the mixing rate of clean ice into dirty ice is sufficient to maintain a steady thickness of dirty ice against thinning from the mean ice flow. The dirty ice appears to consist of two or more basal components in addition to clean glacial ice. A small amount of soil or permafrost, plus preglacial snow, lake or ground ice could explain the observations.

Three-year efficacy of complex insulin regimens in type 2 diabetes.

PubMed

Holman, Rury R; Farmer, Andrew J; Davies, Melanie J; Levy, Jonathan C; Darbyshire, Julie L; Keenan, Joanne F; Paul, Sanjoy K

2009-10-29

Evidence supporting the addition of specific insulin regimens to oral therapy in patients with type 2 diabetes mellitus is limited. In this 3-year open-label, multicenter trial, we evaluated 708 patients who had suboptimal glycated hemoglobin levels while taking metformin and sulfonylurea therapy. Patients were randomly assigned to receive biphasic insulin aspart twice daily, prandial insulin aspart three times daily, or basal insulin detemir once daily (twice if required). Sulfonylurea therapy was replaced by a second type of insulin if hyperglycemia became unacceptable during the first year of the study or subsequently if glycated hemoglobin levels were more than 6.5%. Outcome measures were glycated hemoglobin levels, the proportion of patients with a glycated hemoglobin level of 6.5% or less, the rate of hypoglycemia, and weight gain. Median glycated hemoglobin levels were similar for patients receiving biphasic (7.1%), prandial (6.8%), and basal (6.9%) insulin-based regimens (P=0.28). However, fewer patients had a level of 6.5% or less in the biphasic group (31.9%) than in the prandial group (44.7%, P=0.006) or in the basal group (43.2%, P=0.03), with 67.7%, 73.6%, and 81.6%, respectively, taking a second type of insulin (P=0.002). [corrected] Median rates of hypoglycemia per patient per year were lowest in the basal group (1.7), higher in the biphasic group (3.0), and highest in the prandial group (5.7) (P<0.001 for the overall comparison). The mean weight gain was higher in the prandial group than in either the biphasic group or the basal group. Other adverse event rates were similar in the three groups. Patients who added a basal or prandial insulin-based regimen to oral therapy had better glycated hemoglobin control than patients who added a biphasic insulin-based regimen. Fewer hypoglycemic episodes and less weight gain occurred in patients adding basal insulin. (Current Controlled Trials number, ISRCTN51125379.) 2009 Massachusetts Medical Society

Effects of phenylalanine, histidine, and leucine on basal and GHRH-stimulated GH secretion and on PRL, insulin, and glucose levels in short children. Comparison with the effects of arginine.

PubMed

Bellone, J; Valetto, M R; Aimaretti, G; Segni, M; Volta, C; Cardimale, G; Baffoni, C; Pasquino, A M; Bernasconi, S; Bartolotta, E; Mucci, M; Ghigo, E

1996-01-01

Of the amino acids arginine is the most potent GH secretagogue in man. It potentiates the GH response to GHRH, exerts a weaker PRL-releasing effect, stimulates insulin and glucagon and induces a biphasic glucose variation. The potency and effects of other amino acids on pituitary and pancreatic hormones need to be clarified. In 43 children with normal short stature (5.3-14.0 yr; 30 M and 13 F) the effects of the infusion of phenylalanine (Phe, 0.08 g/kg), histidine (His, 0.1 g/kg), and leucine (Leu, 0.08 g/kg) on basal and GHRH-stimulated GH secretion and on PRL, insulin and glucose levels were studied and compared with those of arginine at high (hArg, 0.5 g/kg) or low dose (lArg, 0.2 g/kg). Phe increased basal (p < 0.05) but not GHRH-stimulated GH levels, induced PRL and insulin rises (p < 0.03 and p < 0.03), and did not change glycemia. Though a trend toward an increase in basal GH levels was found after His, His and Leu did not significantly modify either basal or GHRH-induced GH secretion nor basal PRL, insulin and glucose levels. Both hArg and lArg increased basal (p < 0.0001 and p < 0.05, respectively) and GHRH-stimulated GH levels (p < 0.006 and p < 0.006). hArg increased both PRL (p < 0.002) and insulin levels (p < 0.005) more (p < 0.0005 and p < 0.004) than lArg (p < 0.005 and p < 0.005), while glucose levels showed a similar increase followed by a similar decrease. We conclude that in childhood: a) Phe significantly increases GH secretion but, differently from Arg, does not potentiate the response to GHRH, suggesting different mechanisms of action of these amino acids; b) differently from His and Leu, Phe is a PRL and insulin secretagogue but is less potent than Arg; c) Arg has the highest stimulatory effect on pituitary and pancreatic hormones.

Use of a novel cell adhesion method and digital measurement to show stimulus-dependent variation in somatic and oral ciliary beat frequency in Paramecium.

PubMed

Bell, Wade E; Hallworth, Richard; Wyatt, Todd A; Sisson, Joseph H

2015-01-01

When Paramecium encounters positive stimuli, the membrane hyperpolarizes and ciliary beat frequency increases. We adapted an established immobilization protocol using a biological adhesive and a novel digital analysis system to quantify beat frequency in immobilized Paramecium. Cells showed low mortality and demonstrated beat frequencies consistent with previous studies. Chemoattractant molecules, reduction in external potassium, and posterior stimulation all increased somatic beat frequency. In all cases, the oral groove cilia maintained a higher beat frequency than mid-body cilia, but only oral cilia from cells stimulated with chemoattactants showed an increase from basal levels. © 2014 The Author(s) Journal of Eukaryotic Microbiology © 2014 International Society of Protistologists.

A primer on clothing systems for cold-weather field work

USGS Publications Warehouse

Denner, Jon

1990-01-01

Conducting field work in cold weather is a demanding task. The most important safety consideration for field personnel is to maintain normal body temperature and avoid hypothermia.The human body adjusts to cold temperatures through different physiological processes. Heat production is enhanced by increases in the rates of basal metabolism, specific dynamic action, and physical exercise, and heat loss is reduced by vasoconstriction.Physiological adaptations alone are inadequate to stop rapid heat loss in cold temperatures. Additional insulation in the form of cold-weather clothing is necessary to retain heat.The most practical method of dressing for winter conditions is the layering system. Wearing multiple thin layers allows one to fine tune the insulation needed for different temperatures and activity levels.

Prokaryotic regulatory systems biology: Common principles governing the functional architectures of Bacillus subtilis and Escherichia coli unveiled by the natural decomposition approach.

PubMed

Freyre-González, Julio A; Treviño-Quintanilla, Luis G; Valtierra-Gutiérrez, Ilse A; Gutiérrez-Ríos, Rosa María; Alonso-Pavón, José A

2012-10-31

Escherichia coli and Bacillus subtilis are two of the best-studied prokaryotic model organisms. Previous analyses of their transcriptional regulatory networks have shown that they exhibit high plasticity during evolution and suggested that both converge to scale-free-like structures. Nevertheless, beyond this suggestion, no analyses have been carried out to identify the common systems-level components and principles governing these organisms. Here we show that these two phylogenetically distant organisms follow a set of common novel biologically consistent systems principles revealed by the mathematically and biologically founded natural decomposition approach. The discovered common functional architecture is a diamond-shaped, matryoshka-like, three-layer (coordination, processing, and integration) hierarchy exhibiting feedback, which is shaped by four systems-level components: global transcription factors (global TFs), locally autonomous modules, basal machinery and intermodular genes. The first mathematical criterion to identify global TFs, the κ-value, was reassessed on B. subtilis and confirmed its high predictive power by identifying all the previously reported, plus three potential, master regulators and eight sigma factors. The functionally conserved cores of modules, basal cell machinery, and a set of non-orthologous common physiological global responses were identified via both orthologous genes and non-orthologous conserved functions. This study reveals novel common systems principles maintained between two phylogenetically distant organisms and provides a comparison of their lifestyle adaptations. Our results shed new light on the systems-level principles and the fundamental functions required by bacteria to sustain life. Copyright © 2012 Elsevier B.V. All rights reserved.

Effects of propranolol and pindolol on plasma ANP levels in humans at rest and during exercise.

PubMed

Bouissou, P; Galen, F X; Richalet, J P; Lartigue, M; Devaux, F; Dubray, C; Atlan, G

1989-08-01

In attempt to elucidate whether the beta-adrenoceptor is involved in the control of atrial natriuretic peptide (ANP) secretion, plasma immunoreactive ANP level was measured at rest, in recumbent and upright positions, and during graded maximal ergocycle exercise in nine healthy male subjects (23 +/- 0.5 years of age) treated for 3 days with nonselective beta-blockers propranolol (150 mg/day) or pindolol (15 mg/day) or with placebo. The effects of beta-blockers, which differ by their hemodynamic actions at rest because of the intrinsic sympathomimetic activity of pindolol, were compared. Maximal O2 consumption (VO2max) during beta-blockade was not significantly different from the placebo value. Resting heart rate was not affected by pindolol treatment but was decreased with propranolol (-10 beats/min). Both beta-blockers caused a reduction in heart rate at all the exercise intensities. Mean blood pressure was not affected by beta-blockade at rest but was significantly reduced during exercise. During placebo treatment, plasma ANP increased in response to exercise intensities greater than 65% of VO2max. At 100% VO2max plasma ANP was nearly doubled (101.5 +/- 14 pg/ml) compared with the basal value in upright position (56.6 +/- 15 pg/ml). beta-Blockade caused a marked elevation in plasma ANP at all the levels of activity. Despite different hemodynamic responses to pindolol and propranolol, both beta-blockers produced similar increases in the basal level of plasma ANP. These rises were maintained in the course of exercise tests, and no significant difference was found between propranolol and pindolol. We conclude that beta-adrenoceptor mechanisms are not directly responsible for tonic and exercise-induced ANP secretion in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired glucocorticoid-mediated HPA axis negative feedback induced by juvenile social isolation in male rats.

PubMed

Boero, Giorgia; Pisu, Maria Giuseppina; Biggio, Francesca; Muredda, Laura; Carta, Gianfranca; Banni, Sebastiano; Paci, Elena; Follesa, Paolo; Concas, Alessandra; Porcu, Patrizia; Serra, Mariangela

2018-05-01

We previously demonstrated that socially isolated rats at weaning showed a significant decrease in corticosterone and adrenocorticotropic hormone (ACTH) levels, associated with an enhanced response to acute stressful stimuli. Here we shown that social isolation decreased levels of total corticosterone and of its carrier corticosteroid-binding globulin, but did not influence the availability of the free active fraction of corticosterone, both under basal conditions and after acute stress exposure. Under basal conditions, social isolation increased the abundance of glucocorticoid receptors, while it decreased that of mineralocorticoid receptors. After acute stress exposure, socially isolated rats showed long-lasting corticosterone, ACTH and corticotrophin releasing hormone responses. Moreover, while in the hippocampus and hypothalamus of group-housed rats glucocorticoid receptors expression increased with time and reached a peak when corticosterone levels returned to basal values, in socially isolated rats expression of glucocorticoid receptors did not change. Finally, social isolation also affected the hypothalamic endocannabinoid system: compared to group-housed rats, basal levels of anandamide and cannabinoid receptor type 1 were increased, while basal levels of 2-arachidonoylglycerol were decreased in socially isolated rats and did not change after acute stress exposure. The present results show that social isolation in male rats alters basal HPA axis activity and impairs glucocorticoid-mediated negative feedback after acute stress. Given that social isolation is considered an animal model of several neuropsychiatric disorders, such as generalized anxiety disorder, depression, post-traumatic stress disorder and schizophrenia, these data could contribute to better understand the alterations in HPA axis activity observed in these disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

Enhanced mitochondrial complex gene function and reduced liver size may mediate improved feed efficiency of beef cattle during compensatory growth

USDA-ARS?s Scientific Manuscript database

Growing ruminants maintained under dietary restriction for extended periods will exhibit compensatory growth when reverted to ad libitum feeding. This period of compensatory growth is associated with increased feed efficiency, lower basal energy requirements, and changes in circulating concentration...

Dynamic thiol/disulphide homeostasis in patients with basal cell carcinoma.

PubMed

Demirseren, Duriye Deniz; Cicek, Cagla; Alisik, Murat; Demirseren, Mustafa Erol; Aktaş, Akın; Erel, Ozcan

2017-09-01

The aim of this study is to measure and compare the dynamic thiol/disulphide homeostasis of patients with basal cell carcinoma and healthy subjects with a newly developed and original method. Thirty four patients attending our outpatient clinic and clinically and histopathologically diagnosed as nodular basal cell carcinoma, and age and gender matched 30 healthy individuals have been involved in the study. Thiol/disulphide homeostasis tests have been measured with a novel automatic spectrophotometric method developed and the results have been compared statistically. Serum native thiol and disulphide levels in the patient and control group show a considerable variance statistically (p = 0.028, 0.039, respectively). Total thiol levels do not reveal a considerable variation (p = 0.094). Disulphide/native thiol ratios and native thiol/total thiol ratios also show a considerable variance statistically (p = 0.012, 0.013, 0.010, respectively). Thiol disulphide homeostasis in patients with basal cell carcinoma alters in the way that disulphide gets lower and thiols get higher. Thiol/disulphide level is likely to have a role in basal cell carcinoma pathogenesis.

Single-Nucleotide Polymorphisms of the MSH2 and MLH1 Genes, Potential Molecular Markers for Susceptibility to the Development of Basal Cell Carcinoma in the Brazilian Population.

PubMed

da Silva Calixto, Poliane; Lopes, Otávio Sérgio; Dos Santos Maia, Mayara; Herrero, Sylvia Satomi Takeno; Longui, Carlos Alberto; Melo, Cynthia Germoglio Farias; de Carvalho Filho, Ivan Rodrigues; Soares, Leonardo Ferreira; de Medeiros, Arnaldo Correia; Delatorre, Plínio; Khayat, André Salim; Burbano, Rommel Rodriguez; Lima, Eleonidas Moura

2018-07-01

Basal cell carcinoma - BCC is considered a multifactorial neoplasm involving genetic, epigenetic and environmental factors. Where UVB radiation is considered the main physical agent involved in BCC carcinogenesis. The Brazil and state of Paraíba are exposed to high levels of UVB rays. The mismatch repair - MMR is important DNA repair mechanisms to maintain replication fidelity. Therefore, single nucleotide polymorphisms (SNPs) in genes encoding proteins involved in MMR may be potential molecular markers of susceptibility to BCC. The objective of this study was to evaluate and describe for the first time the SNPs rs560246973, rs2303425 and rs565410865 and risk of developing BCC. The present study analyzed 100 samples of paraffin-embedded tissue from patients with histopathological diagnosis of BCC and 100 control samples. The results were obtained by genotyping method, Dideoxy Unique Allele Specific - PCR (DSASP). The SNPs rs2303425 were not associated with Basal Cell Carcinoma. However, the SNPs rs560246973 and rs565410865 was shown to be associated with the development of BCC when compared to control samples (P < 0.0001). The SNPs rs565410865 was also statistical significance between the genotypes of and the age group (p = 0.0027) and tumor location (p = 0,0191). The result suggests that SNPs rs2303425 and rs565410865 are associated with susceptibility to the development of BCC in the Brazilian population and may be considered as potential molecular markers for BCC.

Increased functional connectivity in the resting-state basal ganglia network after acute heroin substitution

PubMed Central

Schmidt, A; Denier, N; Magon, S; Radue, E-W; Huber, C G; Riecher-Rossler, A; Wiesbeck, G A; Lang, U E; Borgwardt, S; Walter, M

2015-01-01

Reinforcement signals in the striatum are known to be crucial for mediating the subjective rewarding effects of acute drug intake. It is proposed that these effects may be more involved in early phases of drug addiction, whereas negative reinforcement effects may occur more in later stages of the illness. This study used resting-state functional magnetic resonance imaging to explore whether acute heroin substitution also induced positive reinforcement effects in striatal brain regions of protracted heroin-maintained patients. Using independent component analysis and a dual regression approach, we compared resting-state functional connectivity (rsFC) strengths within the basal ganglia/limbic network across a group of heroin-dependent patients receiving both an acute infusion of heroin and placebo and 20 healthy subjects who received placebo only. Subsequent correlation analyses were performed to test whether the rsFC strength under heroin exposure correlated with the subjective rewarding effect and with plasma concentrations of heroin and its main metabolites morphine. Relative to the placebo treatment in patients, heroin significantly increased rsFC of the left putamen within the basal ganglia/limbic network, the extent of which correlated positively with patients' feelings of rush and with the plasma level of morphine. Furthermore, healthy controls revealed increased rsFC of the posterior cingulate cortex/precuneus in this network relative to the placebo treatment in patients. Our results indicate that acute heroin substitution induces a subjective rewarding effect via increased striatal connectivity in heroin-dependent patients, suggesting that positive reinforcement effects in the striatum still occur after protracted maintenance therapy. PMID:25803496

Identification and characterization of a gibberellin-regulated protein, which is ASR5, in the basal region of rice leaf sheaths.

PubMed

Takasaki, Hironori; Mahmood, Tariq; Matsuoka, Makoto; Matsumoto, Hiroshi; Komatsu, Setsuko

2008-04-01

Gibberellins (GAs) regulate growth and development in higher plants. To identify GA-regulated proteins during rice leaf sheath elongation, a proteomic approach was used. Proteins from the basal region of leaf sheath in rice seedling treated with GA(3) were analyzed by fluorescence two-dimensional difference gel electrophoresis. The levels of abscisic acid-stress-ripening-inducible 5 protein (ASR5), elongation factor-1 beta, translationally controlled tumor protein, fructose-bisphosphate aldolase and a novel protein increased; whereas the level of RuBisCO subunit binding-protein decreased by GA(3) treatment. ASR5 out of these six proteins was significantly regulated by GA(3) at the protein level but not at the mRNA level in the basal region of leaf sheaths. Since this protein is regulated not only by abscisic acid but also by GA(3), these results indicate that ASR5 might be involved in plant growth in addition to stress in the basal regions of leaf sheaths.

Endocannabinergic modulation of interleukin-1β in mouse hippocampus under basal conditions and after in vivo systemic lipopolysaccharide stimulation.

PubMed

Csölle, Cecília; Sperlágh, Beáta

2011-01-01

Cannabinoids play an important role in the suppression of proinflammatory cytokine production in the periphery and brain. In this study, we explored whether endogenous activation of cannabinoid (CB) 1 receptors (CB1Rs) affects interleukin (IL)-1β levels in the mouse hippocampus under basal conditions and following stimulation with in vivo bacterial lipopolysaccharide (LPS, 250 μg/kg i.p.). IL-1β levels were determined in the hippocampi of wild-type (WT), CB1R-/- and P2X₇ receptor (P2X₇R)-/- mice using an ELISA kit. Basal but not LPS-induced IL-1β levels were downregulated when CB1R function was abrogated by genetic deletion, suggesting that endocannabinoids contributed to basal IL-1β content in the mouse hippocampus. AM251 (3 mg/kg i.p.), an antagonist of CB1Rs, also inhibited basal IL-1β protein in WT but not in CB1R-/- mice. In the absence of P2X₇R, LPS-induced IL-1β production was lower, while the inhibitory effect of CB1R antagonists on basal IL-1β was significantly attenuated. The LPS-induced elevation in IL-1β production was decreased in the presence of AM251 and AM281, with no significant difference between WT and P2X₇R-/- mice. CB1Rs are responsible for the modulation of basal IL-1β levels in the hippocampus, while the effects of CB1 antagonists on systemic LPS-induced IL-1β concentrations are independent of CB1Rs. Copyright © 2011 S. Karger AG, Basel.

Changes of poststimulatory plasma renin activity in women with hyperthyroidism or hypothyroidism in relation to therapy.

PubMed

Marcisz, Czeslaw; Kucharz, Eugene J; Marcisz-Orzel, Magdalena; Poręba, Ryszard; Orzel, Arkadiusz; Sioma-Markowska, Urszula

2011-01-01

The influence of thyroid hormones upon renin-angiotensin-aldosterone system is poorly understood. Under basal conditions, individuals belong to normal, low or high plasma renin activity (PRA) subjects. The study was designed to evaluate basal and poststimulatory PRA and serum aldosterone (Aldo) level in patients with hyperthyroidism or hypothyroidism during therapy. We examined 73 women with hyperthyroidism, 27 women with hypothyroidism and 36 healthy controls. The patients were investigated before initiation of therapy and after attainment of euthyroid state. All subjects were investigated under basal conditions (normal-sodium diet) and after application of a low-sodium diet for three days and upright position for 3 hr. PRA, serum Aldo level, blood pressure, serum sodium, potassium and thyroid hormone levels were determined in all subjects. The subjects were classified as low PRA (<1.0 ng/ml/h), normal PRA (1.0-4.0 ng/ml/h) and high PRA (>4.0 ng/ml/h) individuals according to results obtained under basal conditions. Relatively higher poststimulatory enhancement in PRA was found in patients with hyperthyroidism, especially those with low basal PRA, than in those with hypothyroidism. In women with thyroid dysfunctions poststimulatory increase in Aldo were relative lower than poststimulatory enhancement of PRA. After therapy these difference disappeared. The poststimulatory changes in PRA depended on the basal PRA. Poststimulatory PRA is higher in hyperthyroid women, especially those with low basal PRA. In women with hypothyroidism, basal and poststimulatory PRA is low. Blood pressure and severity of thyroid dysfunction was found to be similar in the patients with low, normal or high basic PRA. In women with thyroid dysfunctions, serum Aldo level and its relative poststimulatory increments are inadequate to changes of PRA; it is suggested that the dissociation in the renin-angiotensin-aldosterone system occurs in hyperthyroid and hypothyroid women.

Effect of dietary carbohydrate source on the development of obesity in agouti transgenic mice.

PubMed

Morris, Kristin L; Zemel, Michael B

2005-01-01

Our objective was to evaluate the effects of a qualitative change in dietary carbohydrate source on body weight and adiposity in a rodent model of diet-induced obesity. We evaluated the effects of high-fat diets (basal) varying in carbohydrate source in aP2-agouti transgenic mice. In the ad libitum study, animals were given free access to the basal diet or one of four test diets for 6 weeks. In two of the diets, dietary carbohydrate was derived from a single source: mung bean noodles (MUNG) or rolled oats (ROLL). The remaining diets were designed to mimic commercially available instant oatmeal with added sugar (IO-S) or flavored instant oatmeal (IO-F). In the energy-restricted study, animals were given ad libitum access to the basal diet for 6 weeks. Subsequently, animals were assigned to one of six treatment groups for 6 weeks. One group was continued on the basal diet ad libitum. The remaining groups were maintained with energy restriction (70% ad libitum) on either the basal, MUNG, ROLL, IO-S, or IO-F diet. Subcutaneous fat pad mass was significantly higher (p<0.05) in the energy-restricted basal and IO-S groups compared with the energy-restricted ROLL diet. Similarly, visceral fat pad mass was significantly lower with ROLL and MUNG diets (p<0.05 for both) compared with basal and IO-S diets, and the insulin:glucose ratio was reduced (by 23% to 34%, p<0.05) in these two diets compared with all others. In ad libitum-fed animals, liver fatty acid synthase expression was 43% to 62% lower (p<0.05) with ROLL and MUNG diets compared with all others. These data suggest that a qualitative change in dietary carbohydrate source modulates body weight and adiposity.

Effect of γ-Aminobutyric Acid-producing Lactobacillus Strain on Laying Performance, Egg Quality and Serum Enzyme Activity in Hy-Line Brown Hens under Heat Stress.

PubMed

Zhu, Y Z; Cheng, J L; Ren, M; Yin, L; Piao, X S

2015-07-01

Heat-stress remains a costly issue for animal production, especially for poultry as they lack sweat glands, and alleviating heat-stress is necessary for ensuring animal production in hot environment. A high γ-aminobutyric acid (GABA)-producer Lactobacillus strain was used to investigate the effect of dietary GABA-producer on laying performance and egg quality in heat-stressed Hy-line brown hens. Hy-Line brown hens (n = 1,164) at 280 days of age were randomly divided into 4 groups based on the amount of freeze-dried GABA-producer added to the basal diet as follows: i) 0 mg/kg, ii) 25 mg/kg, iii) 50 mg/kg, and iv) 100 mg/kg. All hens were subjected to heat-stress treatment through maintaining the temperature and the relative humidity at 28.83±3.85°C and 37% to 53.9%, respectively. During the experiment, laying rate, egg weight and feed intake of hens were recorded daily. At the 30th and 60th day after the start of the experiment, biochemical parameters, enzyme activity and immune activity in serum were measured. Egg production, average egg weight, average daily feed intake, feed conversion ratio and percentage of speckled egg, soft shell egg and misshaped egg were significantly improved (p<0.05) by the increasing supplementation of the dietary GABA-producer. Shape index, eggshell thickness, strength and weight were increased linearly with increasing GABA-producer supplementation. The level of calcium, phosphorus, glucose, total protein and albumin in serum of the hens fed GABA-producing strain supplemented diet was significantly higher (p<0.05) than that of the hens fed the basal diet, whereas cholesterol level was decreased. Compared with the basal diet, GABA-producer strain supplementation increased serum level of glutathione peroxidase (p = 0.009) and superoxide dismutase. In conclusion, GABA-producer played an important role in alleviating heat-stress, the isolated GABA-producer strain might be a potential natural and safe probiotic to use to improve laying performance and egg quality in heat-stressed hens.

Periodic-Zone Model Predictive Control for Diurnal Closed-Loop Operation of an Artificial Pancreas

PubMed Central

Gondhalekar, Ravi; Dassau, Eyal; Zisser, Howard C.; Doyle, Francis J.

2013-01-01

Background The objective of this research is an artificial pancreas (AP) that performs automatic regulation of blood glucose levels in people with type 1 diabetes mellitus. This article describes a control strategy that performs algorithmic insulin dosing for maintaining safe blood glucose levels over prolonged, overnight periods of time and furthermore was designed with outpatient, multiday deployment in mind. Of particular concern is the prevention of nocturnal hypoglycemia, because during sleep, subjects cannot monitor themselves and may not respond to alarms. An AP intended for prolonged and unsupervised outpatient deployment must strategically reduce the risk of hypoglycemia during times of sleep, without requiring user interaction. Methods A diurnal insulin delivery strategy based on predictive control methods is proposed. The so-called “periodic-zone model predictive control” (PZMPC) strategy employs periodically time-dependent blood glucose output target zones and furthermore enforces periodically time-dependent insulin input constraints to modulate its behavior based on the time of day. Results The proposed strategy was evaluated through an extensive simulation-based study and a preliminary clinical trial. Results indicate that the proposed method delivers insulin more conservatively during nighttime than during daytime while maintaining safe blood glucose levels at all times. In clinical trials, the proposed strategy delivered 77% of the amount of insulin delivered by a time-invariant control strategy; specifically, it delivered on average 1.23 U below, compared with 0.31 U above, the nominal basal rate overnight while maintaining comparable, and safe, blood glucose values. Conclusions The proposed PZMPC algorithm strategically prevents nocturnal hypoglycemia and is considered a significant step toward deploying APs into outpatient environments for extended periods of time in full closed-loop operation. PMID:24351171

Generation and multiplication of plantlets from callus derived from Haplopappus gracilus (Nutt.) Gray and their karyotype analysis

NASA Technical Reports Server (NTRS)

Kann, R. P.; O'Connor, S. A.; Levine, H. G.; Krikorian, A. D.

1991-01-01

Unopened flower heads of Haplopappus gracilis (2n = 4) provided primary explants for callus production and subsequent induction of organized growth. Callus was initiated from small (3-5 mm in length) floral buds with benzylaminopurine (BAP) (44.4 micromoles; 10 mg/l) and naphthalene acetic acid (NAA) (0.54 micromole; 0.1 mg/l). Lowering the BAP level to 4.44 micromoles (1 mg/l) but maintaining the NAA level, gave rise to organized but highly compressed shoot growing points from an otherwise undifferentiated callus mass. Shoots selected from such cultures were maintainable and could be proliferated by growing 1-1.5-cm stem tip cuttings on Murashige and Skoog basal medium (solidified with agar) containing 0.444 micromole (0.1 mg/l) BAP and 0.054 micromole (0.01 mg/l) NAA. The stem tip multiplication rates obtainable by these means permit reliable strategies for shoot multiplication or production of rooted plantlets. Prolonged subculture and maintenance of shoots on growth regulator-free medium leads to in vitro flowering and greatly reduces rooting capacity. Karyotype analysis of chromosomes from root tip cells at metaphase and chromosome measurements show that karyologically uniform plantlets (based on chromosome number and morphology) can be obtained.

Dynamics of Nampt/visfatin and high molecular weight adiponectin in response to oral glucose load in obese and lean women.

PubMed

Unlütürk, Uğur; Harmanci, Ayla; Yildiz, Bülent Okan; Bayraktar, Miyase

2010-04-01

High molecular weight adiponectin (HMWA) is the active circulating form of adiponectin. Nampt/visfatin is the enzyme secreted from adipocytes in an active form and is one of the putative regulators of insulin secretion. To investigate the dynamics of total adiponectin (TA), HMWA and Nampt/visfatin in obese and lean women during oral glucose tolerance test (OGTT). We studied normal glucose-tolerant (NGT), age-matched, 30 obese and 30 lean women. All subjects underwent a standard 75 g, 2-h OGTT, and area under the curve (AUC) during OGTT for glucose, insulin, Nampt/visfatin, TA and HMWA was calculated. Body fat mass was assessed by bioimpedance analysis. Results Obese women had significantly higher basal and AUC values for insulin and Nampt/visfatin, whereas basal and AUC-HMWA were significantly lower in this group. Alternatively, obese and lean groups had similar basal and AUC values for glucose and TA. Basal insulin levels were negatively correlated with HMWA levels, but not with basal Nampt/visfatin. AUC-insulin was correlated positively with AUC-visfatin, and negatively with AUC-HMWA. Total and truncal body fat mass showed positive correlation with basal and AUC-visfatin, and negative correlation with basal and AUC-HMWA. In the NGT state, obese women have higher Nampt/visfatin and lower HMWA levels, both basally and in response to oral glucose challenge. The dynamics of Nampt/visfatin and HMWA during OGTT appear to be linked with insulin and adiposity. Counter-regulatory adaptations in HMWA and Nampt/visfatin might have an impact on suggested adipoinsular axis, contributing to maintenance of normal glucose tolerance.

Importance of vagal input in maintaining gastric tone in the dog.

PubMed Central

Azpiroz, F; Malagelada, J R

1987-01-01

1. Using a gastric barostat to quantify variations in gastric tone, we had previously demonstrated that food ingestion or intestinal nutrient perfusion induces gastric relaxation. These data suggested a basal tonic contraction of the stomach during fasting. 2. To determine the role of vagal input in maintaining fasting gastric tone, we prepared two chronic canine models, either isolating both cervical vagal trunks in a cutaneous tunnel or including the supradiaphragmatic vagi within an implanted cooling jacket. In the fasted conscious dogs, we then studied the effect, on gastric tone, of acute and reversible vagal blockade by cooling. 3. Cervical vagal cooling produced a reversible gastric relaxation and increased the heart rate. Supradiaphragmatic vagal cooling produced a similar gastric relaxation without the cardiac effect. 4. Adrenergic blockade did not change either the base-line gastric tone or the cooling-induced relaxation. Adrenaline decreased gastric tone, but vagal cooling still produced a significant relaxation. 5. Atropine alone or combined with adrenergic antagonists produced a gastric relaxation that was not further increased by vagal cooling. Bethanechol increased gastric tone, an effect unchanged by vagal cooling. 6. We conclude that gastric tone during fasting is maintained by a cholinergic input, which is vagally mediated at both the cervical and the supradiaphragmatic levels. Images Fig. 1 PMID:2888879

Common therapeutic mechanisms of pallidal deep brain stimulation for hypo- and hyperkinetic movement disorders

PubMed Central

Iriki, Atsushi; Isoda, Masaki

2015-01-01

Abnormalities in cortico-basal ganglia (CBG) networks can cause a variety of movement disorders ranging from hypokinetic disorders, such as Parkinson's disease (PD), to hyperkinetic conditions, such as Tourette syndrome (TS). Each condition is characterized by distinct patterns of abnormal neural discharge (dysrhythmia) at both the local single-neuron level and the global network level. Despite divergent etiologies, behavioral phenotypes, and neurophysiological profiles, high-frequency deep brain stimulation (HF-DBS) in the basal ganglia has been shown to be effective for both hypo- and hyperkinetic disorders. The aim of this review is to compare and contrast the electrophysiological hallmarks of PD and TS phenotypes in nonhuman primates and discuss why the same treatment (HF-DBS targeted to the globus pallidus internus, GPi-DBS) is capable of ameliorating both symptom profiles. Recent studies have shown that therapeutic GPi-DBS entrains the spiking of neurons located in the vicinity of the stimulating electrode, resulting in strong stimulus-locked modulations in firing probability with minimal changes in the population-scale firing rate. This stimulus effect normalizes/suppresses the pathological firing patterns and dysrhythmia that underlie specific phenotypes in both the PD and TS models. We propose that the elimination of pathological states via stimulus-driven entrainment and suppression, while maintaining thalamocortical network excitability within a normal physiological range, provides a common therapeutic mechanism through which HF-DBS permits information transfer for purposive motor behavior through the CBG while ameliorating conditions with widely different symptom profiles. PMID:26180116

Effect of epigallocatechin gallate on growth performance and antioxidant capacity in heat-stressed broilers.

PubMed

Xue, Bo; Song, Jiao; Liu, Longzhou; Luo, Jingxian; Tian, Guangming; Yang, Ye

2017-10-01

This study investigated the effects of epigallocatechin gallate (EGCG) on the growth performance and antioxidant capacity of 35-d-old broilers exposed to heat stress. Broilers, 14 d of age, were divided into four groups with six replicates per group (eight chickens/replicate). Thermoneutral group (Group TN) was fed the basal diet and maintained at 28°C for 24 h/d. The heat-stressed groups were housed at 35°C for 12 h/d and 28°C for 12 h/d and fed the basal diet supplemented with EGCG at 0, 300 and 600 mg/kg diet (Groups HS0, HS 300 and HS600, respectively). Compared with Group TN, heat-stressed groups showed significantly reduced gain, feed intake and serum total protein and glucose levels; inhibited serum alkaline phosphatase activities; and increased serum levels of uric acid, cholesterol and triglycerides and the activity of serum creatine kinase, lactate dehydrogenase and aspartate aminotransferase (p < 0.05). Compared with Group HS0, Group HS600 exhibited an increased gain and feed intake; and normalised blood parameters and enzyme activities. Compared with Group TN, the expression of antioxidant-related liver proteins was decreased in Group HS0 and increased in Groups HS300 and HS600 (p < 0.05). The results suggest that EGCG can improve the growth performance and alleviate the oxidant damage by modulating the antioxidant properties of broilers.

Studies on the mechanism of salicylate-induced increase of insulin secretion in man.

PubMed

Giugliano, D; Cozzolino, D; Ceriello, A; Cerciello, T; Varano, R; Saccomanno, F; Torella, R

1988-01-01

Salicylate compounds are known to increase basal and stimulated insulin secretion in man. In our studies, infusion of lysine acetylsalicylate (72 mg/min) increased basal insulin levels and amplified insulin responses to glucose (5 g i.v.), arginine (5 g i.v.) and tolbutamide (1 g i.v.). Verapamil, an organic calcium antagonist, did not modify LAS-induced increase of basal insulin levels, but reduced the effect of LAS on glucose-induced insulin secretion. Calcitonin and somatostatin, two agents that inhibit basal and glucose-stimulated insulin secretion, inhibited the insulin response to glucose in presence of LAS infusion. The ability of salicylate compounds to augment insulin secretion might be due to multiple sites of action in the Beta-cells.

Plasma catecholamine levels before and after paroxetine treatment in patients with panic disorder.

PubMed

Oh, Jae-Young; Yu, Bum-Hee; Heo, Jung-Yoon; Yoo, Ikki; Song, Hyemin; Jeon, Hong Jin

2015-02-28

Catecholamines such as norepinephrine, epinephrine, and dopamine are closely related to the autonomic nervous system, suggesting that panic disorder may involve elevated catecholamine levels. This study investigated basal and posttreatment catecholamine levels in patients with panic disorder. A total of 29 patients with panic disorder and 23 healthy controls participated in the study. Panic disorder patients received paroxetine treatment for 12 weeks after clinical tests and examination had been conducted. We investigated the difference in basal levels of catecholamine and measured the changes in catecholamine levels before and after drug treatment in panic disorder patients. The basal plasma epinephrine (48.87±6.18 pg/ml) and dopamine (34.87±3.57 pg/ml) levels of panic disorder patients were significantly higher than those (34.79±4.72 pg/ml and 20.40±3.53 pg/ml) of the control group. However, basal plasma norepinephrine levels did not show statistically significant differences between patients and controls. After drug therapy, plasma catecholamine levels were nonsignificantly decreased and norepinephrine levels showed a tendency toward a decrease that did not reach significance. In conclusion, this study suggests the possibility of a baseline increase of plasma catecholamine levels and activation of sympathetic nervous systems in patients with panic disorder which may normalize after treatment with paroxetine. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Amino acids augment muscle protein synthesis in neonatal pigs during acute endotoxemia by stimulating mTOR-dependent translation initiation

USDA-ARS?s Scientific Manuscript database

In skeletal muscle of adults, sepsis reduces protein synthesis by depressing translation initiation and induces resistance to branched-chain amino acid stimulation. Normal neonates maintain a high basal muscle protein synthesis rate that is sensitive to amino acid stimulation. In the present study...

[Duration of bronchodilator effect of inhaled Salmeterol (dry powder x metered dose inhaler) in children with acute asthma attack].

PubMed

Solé, D; Rizzo, M C; Porto, I M; Gomez, I D; Sano, F; Figueiredo, M A; Naspitz, C K

1996-01-01

Patients during a mild to moderate acute attack of asthma (FEV1: 50 - 80% of predicted) were treated with Salmeterol MDI - 50mcg or Rotadisk - 50mcg or Salbutamol (MDI -200mcg). The children were followed by Spirometry, measuring FEV1 (basal) and after treatment: at 30 minutes, 60 minutes and thereafter every 60 minutes until 780 minutes, if the patients maintained the FEV1 above 80% of the predicted value and/or an increment of 20% in the VEF1 basal value. The Salmeterol group showed a significant bronchodilation at 60 minutes which was maintained in half of the patients up to 9 hours. This was not observed in the Salbutamol group: the peak bronchodilatation was observed at 30 minutes and the bronchodilation effect was observed in half of the patients up to 6 hours. There were no significant differences between both presentations of Salmeterol. This drug allowed a prolonged bronchodilator effect and is, according to the several consensus on management of asthma, an adequate option in the treatment of moderate to severe asthma.

Magellanic penguin telomeres do not shorten with age with increased reproductive effort, investment, and basal corticosterone.

PubMed

Cerchiara, Jack A; Risques, Rosa Ana; Prunkard, Donna; Smith, Jeffrey R; Kane, Olivia J; Boersma, P Dee

2017-08-01

All species should invest in systems that enhance longevity; however, a fundamental adult life-history trade-off exists between the metabolic resources allocated to maintenance and those allocated to reproduction. Long-lived species will invest more in reproduction than in somatic maintenance as they age. We investigated this trade-off by analyzing correlations among telomere length, reproductive effort and output, and basal corticosterone in Magellanic penguins ( Spheniscus magellanicus ). Telomeres shorten with age in most species studied to date, and may affect adult survival. High basal corticosterone is indicative of stressful conditions. Corticosterone, and stress, has been linked to telomere shortening in other species. Magellanic penguins are a particularly good model organism for this question as they are an unusually long-lived species, exceeding their mass-adjusted predicted lifespan by 26%. Contrary to our hypothesis, we found adults aged 5 years to over 24 years of age had similar telomere lengths. Telomeres of adults did not shorten over a 3-year period, regardless of the age of the individual. Neither telomere length, nor the rate at which the telomeres changed over these 3 years, correlated with breeding frequency or investment. Older females also produced larger volume clutches until approximately 15 years old and larger eggs produced heavier fledglings. Furthermore, reproductive success ( chicks fledged/eggs laid ) is maintained as females aged. Basal corticosterone, however, was not correlated with telomere length in adults and suggests that low basal corticosterone may play a role in the telomere maintenance we observed. Basal corticosterone also declined during the breeding season and was positively correlated with the age of adult penguins. This higher basal corticosterone in older individuals, and consistent reproductive success, supports the prediction that Magellanic penguins invest more in reproduction as they age. Our results demonstrate that telomere maintenance may be a component of longevity even with increased reproductive effort, investment, and basal corticosterone.

Anticipatory guidance in type 2 diabetes to improve disease management; next steps after basal insulin.

PubMed

Johnson, Eric L; Frias, Juan P; Trujillo, Jennifer M

2018-05-01

The alarming rise in the number of people living with type 2 diabetes (T2D) presents primary care physicians with increasing challenges associated with long-term chronic disease care. Studies have shown that the majority of patients are not achieving or maintaining glycemic goals, putting them at risk of a wide range of diabetes-related complications. Disease- and self-management programs have been shown to help patients improve their glycemic control, and are likely to be of particular benefit for patients with diabetes dealing with these issues. Anticipatory guidance is an individualized, proactive approach to patient education and counseling by a health-care professional to support patients in better coping with problems before they arise. It has been shown to improve disease outcomes in a variety of chronic conditions, including diabetes. While important at all stages, anticipatory guidance may be of particular importance during changes in treatment regimens, and especially during transition to, and escalation of, insulin-based regimens. The aim of this article is to provide advice to physicians on anticipatory guidance for basal-insulin dosing, focusing on appropriate basal-insulin-dose increase and prevention of potentially deleterious basal-insulin doses, so called overbasalization. It also provides an overview of new treatment options for patients with T2D who are not well controlled on basal-insulin therapy, fixed-ratio combinations of basal insulin and glucagon-like peptide-1 receptor agonists, and advice on the type of anticipatory guidance needed to ensure safe and appropriate switching to these therapies.

The Readability Levels of the 1981 Scott, Foresman and Co. Basal Texts and Their Comparison with the 1978 Edition.

ERIC Educational Resources Information Center

Ackerman, Bonnie

Fry's Readability Graph was used to determine the readability levels of the 1981 Scott, Foresman and Co. basal textbook series for grades one through six. The readability levels were then compared to those established for the 1978 edition. In the 1981 edition, all stories were handscored. Poems, skill lessons, and plays were not examined in order…

The unique endocrine milieu of the fetus.

PubMed Central

Fisher, D A

1986-01-01

Table II summarizes in tabular form the major features of the fetal endocrine milieu discussed in the foregoing pages. The mammalian fetus develops in an environment where respiration, alimentation, and excretory functions are provided by the placenta. Fetal tissue metabolism is oriented largely to anabolism; body temperature is modulated by maternal metabolism, and fetal tissue thermogenesis is maintained at a basal level. Tissue and organ growth appear to be regulated by growth factors which probably function by autocrine or paracrine mechanisms during most of gestation (72, 146-148). In this milieu conventional endocrine control systems are largely redundant, and other transient systems more appropriate to the intrauterine environment have evolved. We have developed some insights into these systems, but much more information is necessary before we can truly understand this fascinating environment. PMID:3018041

Successful implantation of physiologically functional bioengineered mouse internal anal sphincter.

PubMed

Raghavan, Shreya; Miyasaka, Eiichi A; Hashish, Mohamed; Somara, Sita; Gilmont, Robert R; Teitelbaum, Daniel H; Bitar, Khalil N

2010-08-01

We have previously developed bioengineered three-dimensional internal anal sphincter (IAS) rings from circular smooth muscle cells isolated from rabbit and human IAS. We provide proof of concept that bioengineered mouse IAS rings are neovascularized upon implantation into mice of the same strain and maintain concentric smooth muscle alignment, phenotype, and IAS functionality. Rings were bioengineered by using smooth muscle cells from the IAS of C57BL/6J mice. Bioengineered mouse IAS rings were implanted subcutaneously on the dorsum of C57BL/6J mice along with a microosmotic pump delivering fibroblast growth factor-2. The mice remained healthy during the period of implantation, showing no external signs of rejection. Mice were killed 28 days postsurgery and implanted IAS rings were harvested. IAS rings showed muscle attachment, neovascularization, healthy color, and no external signs of infection or inflammation. Assessment of force generation on harvested IAS rings showed the following: 1) spontaneous basal tone was generated in the absence of external stimulation; 2) basal tone was relaxed by vasoactive intestinal peptide, nitric oxide donor, and nifedipine; 3) acetylcholine and phorbol dibutyrate elicited rapid-rising, dose-dependent, sustained contractions repeatedly over 30 min without signs of muscle fatigue; and 4) magnitudes of potassium chloride-induced contractions were 100% of peak maximal agonist-induced contractions. Our preliminary results confirm the proof of concept that bioengineered rings are neovascularized upon implantation. Harvested rings maintain smooth muscle alignment and phenotype. Our physiological studies confirm that implanted rings maintain 1) overall IAS physiology and develop basal tone, 2) integrity of membrane ionic characteristics, and 3) integrity of membrane associated intracellular signaling transduction pathways for contraction and relaxation by responding to cholinergic, nitrergic, and VIP-ergic stimulation. IAS smooth muscle tissue could thus be bioengineered for the purpose of implantation to serve as a potential graft therapy for dysfunctional internal anal sphincter in fecal incontinence.

Subglacial conditions at a sticky spot along Kamb Ice Stream, West Antarctica

USGS Publications Warehouse

Peters, L.E.; Anandakrishnan, S.

2007-01-01

We present the results of a seismic reflection experiment performed transverse to flow a few tens of kilometers above the main trunk of Kamb Ice Stream, West Antarctica, where we image a basal high surrounded by variable subglacial conditions. This high rises as much as 200 m above the surrounding bed, acting as a major sticking point that resists fast flow. Application of the amplitude variation with offset (AVO) seismic technique has highlighted regions of frozen sediments along our profile, suggesting that the ice stream is experiencing basal freeze-on in the region. The bedrock high appears to be at least partially draped in sediment cover, with a concentrated area of weak, dilatant till flanking one edge. This dilatant till is further dispersed along our profile, though it does not possess enough continuity to maintain streaming ice conditions. These results support the hypothesis that the ongoing shutdown of Kamb Ice Stream is due to a loss in continuous basal lubrication.

Perlecan expression influences the keratin 15‐positive cell population fate in the epidermis of aging skin

PubMed Central

Dos Santos, Morgan; Michopoulou, Anna; André‐Frei, Valérie; Boulesteix, Sophie; Guicher, Christine; Dayan, Guila; Whitelock, John; Damour, Odile; Rousselle, Patricia

2016-01-01

The epidermis is continuously renewed by stem cell proliferation and differentiation. Basal keratinocytes append the dermal‐epidermal junction, a cell surface‐associated, extracellular matrix that provides structural support and influences their behaviour. It consists of laminins, type IV collagen, nidogens, and perlecan, which are necessary for tissue organization and structural integrity. Perlecan is a heparan sulfate proteoglycan known to be involved in keratinocyte survival and differentiation. Aging affects the dermal epidermal junction resulting in decreased contact with keratinocytes, thus impacting epidermal renewal and homeostasis. We found that perlecan expression decreased during chronological skin aging. Our in vitro studies revealed reduced perlecan transcript levels in aged keratinocytes. The production of in vitro skin models revealed that aged keratinocytes formed a thin and poorly organized epidermis. Supplementing these models with purified perlecan reversed the phenomenon allowing restoration of a well‐differentiated multi‐layered epithelium. Perlecan down‐regulation in cultured keratinocytes caused depletion of the cell population that expressed keratin 15. This phenomenon depended on the perlecan heparan sulphate moieties, which suggested the involvement of a growth factor. Finally, we found defects in keratin 15 expression in the epidermis of aging skin. This study highlighted a new role for perlecan in maintaining the self‐renewal capacity of basal keratinocytes. PMID:26996820

Members of the Oral Microbiota Are Associated with IL-8 Release by Gingival Epithelial Cells in Healthy Individuals

PubMed Central

Schueller, Katharina; Riva, Alessandra; Pfeiffer, Stefanie; Berry, David; Somoza, Veronika

2017-01-01

The triggers for the onset of oral diseases are still poorly understood. The aim of this study was to characterize the oral bacterial community in healthy humans and its association with nutrition, oral hygiene habits, and the release of the inflammatory marker IL-8 from gingival epithelial cells (GECs) with and without stimulation by bacterial endotoxins to identify possible indicator operational taxonomic units (OTUs) associated with inflammatory marker status. GECs from 21 healthy participants (13 females, 8 males) were incubated with or without addition of bacterial lipopolysaccharides (LPSs), and the oral microbiota was profiled using 16S rRNA gene-targeted sequencing. The basal IL-8 release after 6 h was between 9.9 and 98.2 pg/ml, and bacterial communities were characteristic for healthy oral microbiota. The composition of the oral microbiota was associated with basal IL-8 levels, the intake of meat, tea, white wine, sweets and the use of chewing gum, as well as flossing habits, allergies, gender and body mass index. Additionally, eight OTUs were associated with high basal levels of IL-8 and GEC response to LPS, with high basal levels of IL-8, and 1 with low basal levels of IL8. The identification of indicator bacteria in healthy subjects with high levels of IL-8 release is of importance as they may be promising early warning indicators for the possible onset of oral diseases. PMID:28360899

Feeding Jerusalem artichoke reduced skatole level and changed intestinal microbiota in the gut of entire male pigs.

PubMed

Vhile, S G; Kjos, N P; Sørum, H; Overland, M

2012-05-01

Different levels of dried Jerusalem artichoke were fed to entire male pigs 1 week before slaughter. The objective was to investigate the effect on skatole level in the hindgut and in adipose tissue, as well as the effect on microflora and short-chain fatty acids (SCFA) in the hindgut. Five experimental groups (n = 11) were given different dietary treatments 7 days before slaughtering: negative control (basal diet), positive control (basal diet + 9% chicory-inulin), basal diet + 4.1% Jerusalem artichoke, basal diet + 8.1% Jerusalem artichoke and basal diet + 12.2% Jerusalem artichoke. Samples from colon, rectum, faeces and adipose tissue were collected. Effect of dietary treatment on skatole, indole and androstenone levels in adipose tissue and on skatole, indole, pH, dry matter (DM), microbiota and SCFA in the hindgut was evaluated. Feeding increasing levels of Jerusalem artichoke to entire male pigs reduced skatole in digesta from colon and in faeces (linear, P < 0.01). There was also a tendency towards a decreased level of skatole in adipose tissue (linear, P = 0.06). Feeding Jerusalem artichoke decreased DM content in colon and faeces and pH in colon (linear, P < 0.01). Increasing levels of Jerusalem artichoke resulted in a reduced level of Clostridium perfringens in both colon and rectum (linear, P < 0.05) and a tendency towards decreased levels of enterobacteria in colon (linear, P = 0.05). Further, there was an increase in total amount of SCFA (linear, P < 0.05), acetic acid (linear, P < 0.05) and valerianic acid (linear, P < 0.01) in faeces. In conclusion, adding dried Jerusalem artichoke to diets for entire male pigs 1 week before slaughter resulted in a dose-dependent decrease in skatole levels in the hindgut and adipose tissue. The reduced skatole levels might be related to the decrease in C. perfringens and the increase in SCFA with subsequent reduction in pH.

Sucrose diet induced enzymatic and hormonal responses affecting carbohydrate, lipid and energy metabolism in two species differing in insulin availability: spiny and ob/ob mice.

PubMed

Shafrir, E; Trostler, N

1984-01-01

The low-insulin responding spiny mice (Acomys cahirinus), maintained on a 50% sucrose diet vs isocaloric regular diet, responded with an impressive increase in the activity of hepatic enzymes of glycolysis and lipogenesis and in hyperlipidemia. There was no hyperinsulinemia or hyperglycemia and spiny mice did not gain weight on sucrose due to loss of adipose tissue. Serum T3 levels rose 1.8 fold and the activity of the hepatic mitochondrial FAD-glycerol-3-phosphate oxidase became induced 2.6 fold representing the enhancement of multiple, T3-dependent, energy-consuming metabolic cycles. An increased TG lipolysis in adipose tissue was also observed. C57BL/6J ob/ob mice were markedly hyperinsulinemic and gained weight on sucrose almost as much as those on regular diet, without changes in serum glucose or insulin. Serum triglyceride level decreased, whereas liver triglycerides accumulated markedly. The extent of the increase in hepatic enzyme activities related to lipogenesis was much lower both in the ob/ob mice and their lean siblings, than in spiny mice, but the basal enzyme activities in ob/ob mice were remarkably elevated. Serum T3 level was also elevated already on the regular diet and rose only slightly on sucrose. Basal glycerol phosphate oxidase activity in ob/ob mice exceeded that in spiny mice and rose only marginally on sucrose. Adipose tissue lipolysis was not increased. Thus, sucrose diet by enhancing the T3 production appeared to activate protective mechanism against weight gain in normoinsulinemic spiny mice, whereas the full expression of these mechanisms appeared to be precluded by the hyperinsulinemia of ob/ob mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced drought and heat stress tolerance of tobacco plants with ectopically enhanced cytokinin oxidase/dehydrogenase gene expression

PubMed Central

Macková, Hana; Hronková, Marie; Dobrá, Jana; Turečková, Veronika; Novák, Ondřej; Lubovská, Zuzana; Motyka, Václav; Haisel, Daniel; Hájek, Tomáš; Prášil, Ilja Tom; Gaudinová, Alena; Štorchová, Helena; Ge, Eva; Werner, Tomáš; Schmülling, Thomas; Vanková, Radomíra

2013-01-01

Responses to drought, heat, and combined stress were compared in tobacco (Nicotiana tabacum L.) plants ectopically expressing the cytokinin oxidase/dehydrogenase CKX1 gene of Arabidopsis thaliana L. under the control of either the predominantly root-expressed WRKY6 promoter or the constitutive 35S promoter, and in the wild type. WRKY6:CKX1 plants exhibited high CKX activity in the roots under control conditions. Under stress, the activity of the WRKY6 promoter was down-regulated and the concomitantly reduced cytokinin degradation coincided with raised bioactive cytokinin levels during the early phase of the stress response, which might contribute to enhanced stress tolerance of this genotype. Constitutive expression of CKX1 resulted in an enlarged root system, a stunted, dwarf shoot phenotype, and a low basal level of expression of the dehydration marker gene ERD10B. The high drought tolerance of this genotype was associated with a relatively moderate drop in leaf water potential and a significant decrease in leaf osmotic potential. Basal expression of the proline biosynthetic gene P5CSA was raised. Both wild-type and WRKY6:CKX1 plants responded to heat stress by transient elevation of stomatal conductance, which correlated with an enhanced abscisic acid catabolism. 35S:CKX1 transgenic plants exhibited a small and delayed stomatal response. Nevertheless, they maintained a lower leaf temperature than the other genotypes. Heat shock applied to drought-stressed plants exaggerated the negative stress effects, probably due to the additional water loss caused by a transient stimulation of transpiration. The results indicate that modulation of cytokinin levels may positively affect plant responses to abiotic stress through a variety of physiological mechanisms. PMID:23669573

Effect of antisense oligodeoxynucleotides for ICAM-1 on renal ischaemia–reperfusion injury in the anaesthetised rat

PubMed Central

Kiew, Lik Voon; Munavvar, Abdul Sattar; Law, Chung Hiong; Azizan, Abdullah Nor; Nazarina, Abdul Rahman; Sidik, Khalifah; Johns, Edward J

2004-01-01

An antisense oligodeoxynucleotide (As-ODN) to the 3′ untranslated region of the mRNA sequence expressing the intracellular adhesion molecule-1 (ICAM-1) was employed to determine ICAM-1's role in renal ischaemia–reperfusion injury in the rat. Wistar-Kyoto rats receiving i.v. either lipofectin–As-ODN (As-ODN group), lipofectin–reverse ODN (Rv-ODN group) or lipofectin (ischaemia control group) 8 h prior to study were anaesthetized and subjected to 30 min of renal artery occlusion. Renal haemodynamic and excretory parameters were monitored before and after renal ischaemia. On termination of the study renal tissue was subjected to histological and Western blot analysis. Renal blood flow decreased in the 3 h post-ischaemia period in the ischaemia control and Rv-ODN groups, but was maintained in the As-ODN group. Glomerular filtration rate was depressed initially but gradually increased to 10% above basal levels in the ischaemia control and Rv-ODN groups, but was below basal levels (20%) in the As-ODN group. There was a three- to fourfold increase in sodium and water excretion following ischaemia in the ischaemia control and reverse-ODN groups but not in the As-ODN treated group. The As-ODN ameliorated the histological evidence of ischaemic damage and reduced ICAM-1 protein levels to a greater extent in the medulla than cortex. These observations suggested that in the post-ischaemic period afferent and efferent arteriolar tone was increased with a loss of reabsorptive capacity which was in part due to ICAM-1. The possibility arises that the action of ICAM-1 at vascular and tubular sites in the deeper regions of the kidney contributes to the ischaemia–reperfusion injury. PMID:15047774

Effects of grazing management treatment on grassland plant communities and prairie grouse habitat

Treesearch

Llewellyn L. Manske; William T. Barker; Mario E. Biondini

1988-01-01

Seasonlong grazing treatments show no benefit to grass basal cover and visual obstruction is not adequate. Pastures with one grazing period in mid season show no positive change in grass basal cover but have better visual obstruction than seasonlong. Deferred grazing decreases basal cover of warm season grasses and visual obstruction reduced to inadequate levels the...

Complex Dynamics in the Basal Ganglia: Health and Disease Beyond the Motor System.

PubMed

Andres, Daniela S; Darbin, Olivier

2018-01-01

The rate and oscillatory hypotheses are the two main current frameworks of basal ganglia pathophysiology. Both hypotheses have emerged from research on movement disorders sharing similar conceptualizations. These pathological conditions are classified either as hypokinetic or hyperkinetic, and the electrophysiological hallmarks of basal ganglia dysfunction are categorized as prokinetic or antikinetic. Although nonmotor symptoms, including neurobehavioral symptoms, are a key manifestation of basal ganglia dysfunction, they are uncommonly accounted for in these models. In patients with Parkinson's disease, the broad spectrum of motor symptoms and neurobehavioral symptoms challenges the concept that basal ganglia disorders can be classified into two categories. The profile of symptoms of basal ganglia dysfunction is best characterized by a breakdown of information processing, accompanied at an electrophysiological level by complex alterations of spiking activity from basal ganglia neurons. The authors argue that the dynamics of the basal ganglia circuit cannot be fully characterized by linear properties such as the firing rate or oscillatory activity. In fact, the neuronal spiking stream of the basal ganglia circuit is irregular but has temporal structure. In this context, entropy was introduced as a measure of probabilistic irregularity in the temporal organization of neuronal activity of the basal ganglia, giving place to the entropy hypothesis of basal ganglia pathology. Obtaining a quantitative characterization of irregularity of spike trains from basal ganglia neurons is key to elaborating a new framework of basal ganglia pathophysiology.

Thinning increases climatic resilience of red pine

USGS Publications Warehouse

Magruder, Matthew; Chhin, Sophan; Palik, Brian; Bradford, John B.

2013-01-01

Forest management techniques such as intermediate stand-tending practices (e.g., thinning) can promote climatic resiliency in forest stands by moderating tree competition. Residual trees gain increased access to environmental resources (i.e., soil moisture, light), which in turn has the potential to buffer trees from stressful climatic conditions. The influences of climate (temperature and precipitation) and forest management (thinning method and intensity) on the productivity of red pine (Pinus resinosa Ait.) in Michigan were examined to assess whether repeated thinning treatments were able to increase climatic resiliency (i.e., maintaining productivity and reduced sensitivity to climatic stress). The cumulative productivity of each thinning treatment was determined, and it was found that thinning from below to a residual basal area of 14 m2·ha−1 produced the largest average tree size but also the second lowest overall biomass per acre. On the other hand, the uncut control and the thinning from above to a residual basal area of 28 m2·ha−1 produced the smallest average tree size but also the greatest overall biomass per acre. Dendrochronological methods were used to quantify sensitivity of annual radial growth to monthly and seasonal climatic factors for each thinning treatment type. Climatic sensitivity was influenced by thinning method (i.e., thinning from below decreased sensitivity to climatic stress more than thinning from above) and by thinning intensity (i.e., more intense thinning led to a lower climatic sensitivity). Overall, thinning from below to a residual basal area of 21 m2·ha−1 represented a potentially beneficial compromise to maximize tree size, biomass per acre, and reduced sensitivity to climatic stress, and, thus, the highest level of climatic resilience.

Protracted effects of chronic stress on serotonin-dependent thermoregulation.

PubMed

Natarajan, Reka; Northrop, Nicole A; Yamamoto, Bryan K

2015-01-01

Chronic stress is known to affect serotonin (5HT) neurotransmission in the brain and to alter body temperature. The body temperature is controlled in part, by the medial preoptic area (mPOA) of the hypothalamus. To investigate the effect of chronic stress on 5HT and how it affects body temperature regulation, we examined whether exposure to a chronic unpredictable stress (CUS) paradigm produces long-term alterations in thermoregulatory function of the mPOA through decreased 5HT neurotransmission. Adult male Sprague-Dawley rats underwent 21 d of CUS. Four days after the last stress exposure, basal body temperature in the home cage and body temperature in a cold room maintained at 10 °C were recorded. The CUS rats had significantly higher subcutaneous basal body temperature at 13:00 h compared to unstressed (NoStress) rats. Whereas the NoStress rats were able to significantly elevate body temperature from basal levels at 30 and 60 min of exposure to the cold room, the CUS rats showed a hypothermic response to the cold. Treatment during CUS with metyrapone, a corticosterone synthesis inhibitor, blocked stress-induced decrease in body temperature in response to the cold challenge. CUS also decreased 5HT transporter protein immunoreactivity in the mPOA and 5HT2A/C agonist injection into the mPOA after CUS exposure caused stressed rats to exhibit a sensitized hyperthermic response to cold. These results indicate that the CUS induced changes to the 5HTergic system alter mPOA function in thermoregulation. These findings help us to explain the mechanisms underlying chronic stress-induced disorders such as chronic fatigue syndrome wherein long lasting thermoregulatory deficits are observed.

Basal-Bolus Insulin Therapy with Gla-300 During Hospitalization Reduces Nocturnal Hypoglycemia in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Study.

PubMed

Okajima, Fumitaka; Nakamura, Yuko; Yamaguchi, Yuji; Shuto, Yuki; Kato, Katsuhito; Sugihara, Hitoshi; Emoto, Naoya

2018-04-04

Although reduction in the incidence of nocturnal hypoglycemia, as estimated by symptom or self-monitored plasma glucose, was shown to be more pronounced with 300 units/mL insulin glargine (Gla-300) than with 100 units/mL insulin glargine (Gla-100) in type 2 diabetes patients, the exact frequency of nocturnal hypoglycemia estimated with continuous glucose monitoring (CGM) has not been reported. Forty patients with type 2 diabetes who were admitted for glycemic control with basal-bolus insulin therapy (BBT) were randomized into the Gla-100 and Gla-300 groups. Insulin doses were adjusted to maintain blood glucose levels within 100-120 mg/dL at each meal. Plasma glucose and C-peptide profiles were estimated serially after admission and before discharge. Daily CGM was also performed before discharge. In the Gla-100 and Gla-300 groups, the mean duration of hospitalization was 15 ± 2 and 15 ± 1 days, respectively, and the mean basal insulin dose before discharge was 13 ± 7 and 15 ± 10 units, respectively. The dose of meal-time insulin was not different between the two groups. Compared with the Gla-300 group, the Gla-100 group had significantly lower nocturnal profiles of plasma glucose and C-peptide, but significantly higher frequency of CGM-estimated nocturnal hypoglycemia (10.7% ± 18.4% versus 1.2% ± 3.6%, P = 0.033). In type 2 diabetic patients, reduction in the incidence of CGM-estimated nocturnal hypoglycemia by BBT under tightly controlled diet therapy was higher with Gla-300 than with Gla-100. UMIN clinical trials registry (UMIN000023360).

Pharmacological dissection of the cellular mechanisms associated to the spontaneous and the mechanically stimulated ATP release by mesentery endothelial cells: roles of thrombin and TRPV.

PubMed

Verónica Donoso, M; Hernández, Felipe; Villalón, Tania; Acuña-Castillo, Claudio; Pablo Huidobro-Toro, J

2018-06-01

Endothelial cells participate in extracellular ATP release elicited by mechanosensors. To characterize the dynamic interactions between mechanical and chemical factors that modulate ATP secretion by the endothelium, we assessed and compared the mechanisms participating in the spontaneous (basal) and mechanically stimulated secretion using primary cultures of rat mesentery endothelial cells. ATP/metabolites were determined in the cell media prior to (basal) and after cell media displacement or a picospritzer buffer puff used as mechanical stimuli. Mechanical stimulation increased extracellular ATP that peaked within 1 min, and decayed to basal values in 10 min. Interruption of the vesicular transport route consistently blocked the spontaneous ATP secretion. Cells maintained in media lacking external Ca 2+ elicited a spontaneous rise of extracellular ATP and adenosine, but failed to elicit a further extracellular ATP secretion following mechanical stimulation. 2-APB, a TRPV agonist, increased the spontaneous ATP secretion, but reduced the mechanical stimulation-induced nucleotide release. Pannexin1 or connexin blockers and gadolinium, a Piezo1 blocker, reduced the mechanically induced ATP release without altering spontaneous nucleotide levels. Moreover, thrombin or related agonists increased extracellular ATP secretion elicited by mechanical stimulation, without modifying spontaneous release. In sum, present results allow inferring that the spontaneous, extracellular nucleotide secretion is essentially mediated by ATP containing vesicles, while the mechanically induced secretion occurs essentially by connexin or pannexin1 hemichannel ATP transport, a finding fully supported by results from Panx1 -/- rodents. Only the latter component is modulated by thrombin and related receptor agonists, highlighting a novel endothelium-smooth muscle signaling role of this anticoagulant.

Protracted effects of chronic stress on serotonin dependent thermoregulation

PubMed Central

Natarajan, Reka; Northrop, Nicole A.; Yamamoto, Bryan K.

2016-01-01

Chronic stress is known to affect serotonin (5HT) neurotransmission in the brain and to alter body temperature. Body temperature is controlled in part, by the medial preoptic area of the hypothalamus (mPOA). To investigate the effect of chronic stress on 5HT and how it affects body temperature regulation, we examined whether exposure to a chronic unpredictable stress paradigm (CUS) produces long-term alterations in thermoregulatory function of the mPOA through decreased 5HT neurotransmission. Adult male Sprague-Dawley rats underwent 21 days of CUS. Four days after last stress exposure, basal body temperature in the home cage and body temperature in a cold room maintained at 10°C were recorded. CUS rats had significantly higher subcutaneous basal body temperature at 13:00 h compared to unstressed (NoStress) rats. Whereas the NoStress rats were able to significantly elevate body temperature from basal levels at 30 and 60 min of exposure to the cold room, the CUS rats showed a hypothermic response to the cold. Treatment during CUS with metyrapone, a corticosterone synthesis inhibitor, blocked stress-induced decrease in body temperature in response to the cold challenge. CUS also decreased 5HT transporter protein immunoreactivity in the mPOA and 5HT2A/C agonist injection into the mPOA after CUS exposure caused stressed rats to exhibit a sensitized hyperthermic response to cold. These results indicate that CUS induced changes to the 5HTergic system alters mPOA function in thermoregulation. These findings help explain mechanisms underlying chronic stress induced disorders such as chronic fatigue syndrome wherein long lasting thermoregulatory deficits are observed. PMID:26414686

Energy Intake and Energy Expenditure for Determining Excess Weight Gain in Pregnant Women

PubMed Central

Gilmore, L. Anne; Butte, Nancy F.; Ravussin, Eric; Han, Hongmei; Burton, Jeffrey H.; Redman, Leanne M.

2016-01-01

Objective To conduct a secondary analysis designed to test whether gestational weight gain is due to increased energy intake or adaptive changes in energy expenditures. Methods In this secondary analysis, energy intake and energy expenditure of 45 pregnant women (BMI 18.5–24.9 kg/m2, n=33 and BMI ≥ 25, n=12) were measured preconceptionally 22, and 36 weeks of gestation. Energy intake was calculated as the sum of total energy expenditure measured by doubly labeled water and energy deposition determined by the 4-compartment body composition model. Weight, body composition, and metabolic chamber measurement were completed preconceptionally, 9, 22, and 36 weeks of gestation. Basal metabolic rate was measured by indirect calorimetry in a room calorimeter and activity energy expenditure by doubly labeled water. Results Energy intake from 22 to 36 weeks of gestation was significantly higher in high gainers (n=19) (3437 ± 99 kcal/d) versus low + ideal gainers (n=26) (2687 ± 110 p< .001) within both BMI categories. Basal metabolic rate increased in proportion to gestational weight gain; however, basal metabolic rate adjusted for body composition changes with gestational weight gain was not significantly different between high gainers and low + ideal gainers (151 ± 33 vs. 129 ± 36 kcal/d; p=.66). Activity energy expenditure decreased throughout pregnancy in both groups (low + ideal gainers: −150 ± 70 kcal/d; p=.04 and high gainers: −230 ± 92 kcal/day; p=.01), but there was no difference between high gainers and low + ideal gainers (p=.49). Conclusion Interventions designed to increase adherence to the IOM guidelines for weight gain in pregnancy may have increased efficacy if focused on limiting energy intake while increasing nutrient density and maintaining levels of physical activity. PMID:27054928

A Magnetic Resonance Spectroscopy Study of Lovastatin for Treating Bipolar Mood Disorder: A 4-Week Randomized Double-Blind, Placebo- Controlled Clinical Trial.

PubMed

Lotfi, Mehrzad; Shafiee, Sara; Ghanizadeh, Ahmd; Sigaroudi, Motahar O; Razeghian, Leila

2017-01-01

No trial has examined the effect of lovastatin on the brain metabolites in patients with bipolar mood disorder. Current medications for treating bipolar disorders cause metabolic syndrome. It is supposed that lovastatin not only decreases the rate of metabolic syndrome but also impacts some brain metabolites and their ratio like common treatments that are measured by Magnetic Resonance Spectroscopy. 27 Manic phase patients were randomly allocated into two groups, lovastatin and placebo as their adjuant medication. Clinical symptoms were assessed at baseline, weeks 2, 4. The brain metabolites were measured at baseline and week 4. Regarding the change of clinical symptoms, no significant difference was found between two groups. However, lovastatin significantly increased the level of NAA in cingulate gyrus in comparison to the placebo group. Moreover, lovastatin more than placebo increased creatine in the left basal ganglia. Furthermore, choline/ creatine showed a significant decrease in the left basal ganglia in lovastatin group. Using MRS after treating with lovastatin showed lovastatin increases NAA in cingulate gyrus, indicating the possible effect of NAA for increasing the reduced viable neuron. Moreover, the increment of Cr by lovastatin in the left basal ganglia suggests the role of lovastatin for maintaining energy homeostasis, anti-apoptotic activity and ATP production in bipolar disorder. Some patents using lovastatin as an adjuant therapy for treating bipolar patients and depression in MDD patients are also outlined. This trial was registered in the Iranian Clinical Trials Registry (http://www.irct.ir/) (IRCT201302203930N18). Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cognitive function in elderly marathon runners: cross-sectional data from the marathon trial (APSOEM).

PubMed

Winker, Robert; Lukas, Ina; Perkmann, Thomas; Haslacher, Helmut; Ponocny, Elisabeth; Lehrner, Johann; Tscholakoff, Dimiter; Dal-Bianco, Peter

2010-12-01

Cognitive impairment of the elderly contributes to morbidity, loss of quality of life, and impairment of work ability in aging western societies. Thus strategies to maintain cognitive function at an advanced age imply a great challenge to Occupational Medicine. To study whether intensive endurance exercise training is associated with better cognitive performance and increases brain-derived neurotrophic factor (BDNF) and insulin-like growth factor (IGF). Active elderly marathon runners or bicyclists older than 60 years were recruited and matched with an inactive control group according to age, sex, and education years. After exclusion of various diseases according to the study protocol 56 athletes and 58 controls could be selected for follow-up studies. The influence of endurance training on cognitive function was assessed by the use of the Vienna Neuropsychological Test Battery and the CERAD test battery. Other relevant outcomes were the levels of BDNF, IGF-1, Apo e4 carrier state, and self-ratings. The elderly marathon group performed better only in one specific cognitive task (the Five Point Test, p = 0.04) and almost significantly better in one additional test (the NAI Stroop Test, p = 0.08). Neither BDNF nor IGF-1 was related to the duration of daily exercise and no differences in the basal levels of these humoral growth factors in the exercise and the control cohort were found. Interestingly, we also found significantly decreased BDNF levels in subjects with Alzheimer's disease in the family in spite of the maintained normal cognitive performance (p = 0.01). These results suggest that extensive endurance exercise training might be beneficial for maintaining cognitive function in elderly persons. Our data demonstrate that beneficial endurance training effects are not linked to the upregulation of the examined neurotrophins. Since we found reduced BDNF-levels in subjects with a positive family history of Alzheimer's disease, we speculate that BDNF-reduction might precede cognitive impairment.

The Human Airway Epithelial Basal Cell Transcriptome

PubMed Central

Wang, Rui; Zwick, Rachel K.; Ferris, Barbara; Witover, Bradley; Salit, Jacqueline; Crystal, Ronald G.

2011-01-01

Background The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem/progenitor cells for the other airway cell types. The objective of this study is to better understand human airway epithelial basal cell biology by defining the gene expression signature of this cell population. Methodology/Principal Findings Bronchial brushing was used to obtain airway epithelium from healthy nonsmokers. Microarrays were used to assess the transcriptome of basal cells purified from the airway epithelium in comparison to the transcriptome of the differentiated airway epithelium. This analysis identified the “human airway basal cell signature” as 1,161 unique genes with >5-fold higher expression level in basal cells compared to differentiated epithelium. The basal cell signature was suppressed when the basal cells differentiated into a ciliated airway epithelium in vitro. The basal cell signature displayed overlap with genes expressed in basal-like cells from other human tissues and with that of murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the human airway basal cell signature was characterized by genes encoding extracellular matrix components, growth factors and growth factor receptors, including genes related to the EGF and VEGF pathways. Interestingly, while the basal cell signature overlaps that of basal-like cells of other organs, the human airway basal cell signature has features not previously associated with this cell type, including a unique pattern of genes encoding extracellular matrix components, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels. Conclusion/Significance The human airway epithelial basal cell signature identified in the present study provides novel insights into the molecular phenotype and biology of the stem/progenitor cells of the human airway epithelium. PMID:21572528

A unique enhancer boundary complex on the mouse ribosomal RNA genes persists after loss of Rrn3 or UBF and the inactivation of RNA polymerase I transcription

PubMed Central

Stefanovsky, Victor Y.; Tremblay, Michel G.; Lindsay, Helen; Robinson, Mark D.

2017-01-01

Transcription of the several hundred of mouse and human Ribosomal RNA (rRNA) genes accounts for the majority of RNA synthesis in the cell nucleus and is the determinant of cytoplasmic ribosome abundance, a key factor in regulating gene expression. The rRNA genes, referred to globally as the rDNA, are clustered as direct repeats at the Nucleolar Organiser Regions, NORs, of several chromosomes, and in many cells the active repeats are transcribed at near saturation levels. The rDNA is also a hotspot of recombination and chromosome breakage, and hence understanding its control has broad importance. Despite the need for a high level of rDNA transcription, typically only a fraction of the rDNA is transcriptionally active, and some NORs are permanently silenced by CpG methylation. Various chromatin-remodelling complexes have been implicated in counteracting silencing to maintain rDNA activity. However, the chromatin structure of the active rDNA fraction is still far from clear. Here we have combined a high-resolution ChIP-Seq protocol with conditional inactivation of key basal factors to better understand what determines active rDNA chromatin. The data resolve questions concerning the interdependence of the basal transcription factors, show that preinitiation complex formation is driven by the architectural factor UBF (UBTF) independently of transcription, and that RPI termination and release corresponds with the site of TTF1 binding. They further reveal the existence of an asymmetric Enhancer Boundary Complex formed by CTCF and Cohesin and flanked upstream by phased nucleosomes and downstream by an arrested RNA Polymerase I complex. We find that the Enhancer Boundary Complex is the only site of active histone modification in the 45kbp rDNA repeat. Strikingly, it not only delimits each functional rRNA gene, but also is stably maintained after gene inactivation and the re-establishment of surrounding repressive chromatin. Our data define a poised state of rDNA chromatin and place the Enhancer Boundary Complex as the likely entry point for chromatin remodelling complexes. PMID:28715449

A unique enhancer boundary complex on the mouse ribosomal RNA genes persists after loss of Rrn3 or UBF and the inactivation of RNA polymerase I transcription.

PubMed

Herdman, Chelsea; Mars, Jean-Clement; Stefanovsky, Victor Y; Tremblay, Michel G; Sabourin-Felix, Marianne; Lindsay, Helen; Robinson, Mark D; Moss, Tom

2017-07-01

Transcription of the several hundred of mouse and human Ribosomal RNA (rRNA) genes accounts for the majority of RNA synthesis in the cell nucleus and is the determinant of cytoplasmic ribosome abundance, a key factor in regulating gene expression. The rRNA genes, referred to globally as the rDNA, are clustered as direct repeats at the Nucleolar Organiser Regions, NORs, of several chromosomes, and in many cells the active repeats are transcribed at near saturation levels. The rDNA is also a hotspot of recombination and chromosome breakage, and hence understanding its control has broad importance. Despite the need for a high level of rDNA transcription, typically only a fraction of the rDNA is transcriptionally active, and some NORs are permanently silenced by CpG methylation. Various chromatin-remodelling complexes have been implicated in counteracting silencing to maintain rDNA activity. However, the chromatin structure of the active rDNA fraction is still far from clear. Here we have combined a high-resolution ChIP-Seq protocol with conditional inactivation of key basal factors to better understand what determines active rDNA chromatin. The data resolve questions concerning the interdependence of the basal transcription factors, show that preinitiation complex formation is driven by the architectural factor UBF (UBTF) independently of transcription, and that RPI termination and release corresponds with the site of TTF1 binding. They further reveal the existence of an asymmetric Enhancer Boundary Complex formed by CTCF and Cohesin and flanked upstream by phased nucleosomes and downstream by an arrested RNA Polymerase I complex. We find that the Enhancer Boundary Complex is the only site of active histone modification in the 45kbp rDNA repeat. Strikingly, it not only delimits each functional rRNA gene, but also is stably maintained after gene inactivation and the re-establishment of surrounding repressive chromatin. Our data define a poised state of rDNA chromatin and place the Enhancer Boundary Complex as the likely entry point for chromatin remodelling complexes.

Contributions of glycogen to astrocytic energetics during brain activation.

PubMed

Dienel, Gerald A; Cruz, Nancy F

2015-02-01

Glycogen is the major store of glucose in brain and is mainly in astrocytes. Brain glycogen levels in unstimulated, carefully-handled rats are 10-12 μmol/g, and assuming that astrocytes account for half the brain mass, astrocytic glycogen content is twice as high. Glycogen turnover is slow under basal conditions, but it is mobilized during activation. There is no net increase in incorporation of label from glucose during activation, whereas label release from pre-labeled glycogen exceeds net glycogen consumption, which increases during stronger stimuli. Because glycogen level is restored by non-oxidative metabolism, astrocytes can influence the global ratio of oxygen to glucose utilization. Compensatory increases in utilization of blood glucose during inhibition of glycogen phosphorylase are large and approximate glycogenolysis rates during sensory stimulation. In contrast, glycogenolysis rates during hypoglycemia are low due to continued glucose delivery and oxidation of endogenous substrates; rates that preserve neuronal function in the absence of glucose are also low, probably due to metabolite oxidation. Modeling studies predict that glycogenolysis maintains a high level of glucose-6-phosphate in astrocytes to maintain feedback inhibition of hexokinase, thereby diverting glucose for use by neurons. The fate of glycogen carbon in vivo is not known, but lactate efflux from brain best accounts for the major metabolic characteristics during activation of living brain. Substantial shuttling coupled with oxidation of glycogen-derived lactate is inconsistent with available evidence. Glycogen has important roles in astrocytic energetics, including glucose sparing, control of extracellular K(+) level, oxidative stress management, and memory consolidation; it is a multi-functional compound.

Contributions of Glycogen to Astrocytic Energetics during Brain Activation

PubMed Central

Dienel, Gerald A.; Cruz, Nancy F.

2014-01-01

Glycogen is the major store of glucose in brain and is mainly in astrocytes. Brain glycogen levels in unstimulated, carefully-handled rats are 10-12 mol/g, and assuming that astrocytes account for half the brain mass, astrocytic glycogen content is twice as high. Glycogen turnover is slow under basal conditions, but it is mobilized during activation. There is no net increase in incorporation of label from glucose during activation, whereas label release from pre-labeled glycogen exceeds net glycogen consumption, which increases during stronger stimuli. Because glycogen level is restored by non-oxidative metabolism, astrocytes can influence the global ratio of oxygen to glucose utilization. Compensatory increases in utilization of blood glucose during inhibition of glycogen phosphorylase are large and approximate glycogenolysis rates during sensory stimulation. In contrast, glycogenolysis rates during hypoglycemia are low due to continued glucose delivery and oxidation of endogenous substrates; rates that preserve neuronal function in the absence of glucose are also low, probably due to metabolite oxidation. Modeling studies predict that glycogenolysis maintains a high level of glucose-6-phosphate in astrocytes to maintain feedback inhibition of hexokinase, thereby diverting glucose for use by neurons. The fate of glycogen carbon in vivo is not known, but lactate efflux from brain best accounts for the major metabolic characteristics during activation of living brain. Substantial shuttling coupled with oxidation of glycogen-derived lactate is inconsistent with available evidence. Glycogen has important roles in astrocytic energetics, including glucose sparing, control of extracellular K+ level, oxidative stress management, and memory consolidation; it is a multi-functional compound. PMID:24515302

Estimating parameters for tree basal area growth with a system of equations and seemingly unrelated regressions

Treesearch

Charles E. Rose; Thomas B. Lynch

2001-01-01

A method was developed for estimating parameters in an individual tree basal area growth model using a system of equations based on dbh rank classes. The estimation method developed is a compromise between an individual tree and a stand level basal area growth model that accounts for the correlation between trees within a plot by using seemingly unrelated regression (...

Relation of snowpack Accumulation to Red Pine Stocking

Treesearch

Edward A. Hansen

1969-01-01

A snow accumulation study was conducted in a 33-year-old red pine plantation thinned to different stocking levels. Snowpack water content increased an average of 2 percent for each 10 square feet of basal area reduction, within the range of 60 to 180 square feet of basal area. Reducing plantation stocking from 180 to 60 square feet of basal area per acre would result...

Basal Ganglia Neuromodulation Over Multiple Temporal and Structural Scales—Simulations of Direct Pathway MSNs Investigate the Fast Onset of Dopaminergic Effects and Predict the Role of Kv4.2

PubMed Central

Lindroos, Robert; Dorst, Matthijs C.; Du, Kai; Filipović, Marko; Keller, Daniel; Ketzef, Maya; Kozlov, Alexander K.; Kumar, Arvind; Lindahl, Mikael; Nair, Anu G.; Pérez-Fernández, Juan; Grillner, Sten; Silberberg, Gilad; Hellgren Kotaleski, Jeanette

2018-01-01

The basal ganglia are involved in the motivational and habitual control of motor and cognitive behaviors. Striatum, the largest basal ganglia input stage, integrates cortical and thalamic inputs in functionally segregated cortico-basal ganglia-thalamic loops, and in addition the basal ganglia output nuclei control targets in the brainstem. Striatal function depends on the balance between the direct pathway medium spiny neurons (D1-MSNs) that express D1 dopamine receptors and the indirect pathway MSNs that express D2 dopamine receptors. The striatal microstructure is also divided into striosomes and matrix compartments, based on the differential expression of several proteins. Dopaminergic afferents from the midbrain and local cholinergic interneurons play crucial roles for basal ganglia function, and striatal signaling via the striosomes in turn regulates the midbrain dopaminergic system directly and via the lateral habenula. Consequently, abnormal functions of the basal ganglia neuromodulatory system underlie many neurological and psychiatric disorders. Neuromodulation acts on multiple structural levels, ranging from the subcellular level to behavior, both in health and disease. For example, neuromodulation affects membrane excitability and controls synaptic plasticity and thus learning in the basal ganglia. However, it is not clear on what time scales these different effects are implemented. Phosphorylation of ion channels and the resulting membrane effects are typically studied over minutes while it has been shown that neuromodulation can affect behavior within a few hundred milliseconds. So how do these seemingly contradictory effects fit together? Here we first briefly review neuromodulation of the basal ganglia, with a focus on dopamine. We furthermore use biophysically detailed multi-compartmental models to integrate experimental data regarding dopaminergic effects on individual membrane conductances with the aim to explain the resulting cellular level dopaminergic effects. In particular we predict dopaminergic effects on Kv4.2 in D1-MSNs. Finally, we also explore dynamical aspects of the onset of neuromodulation effects in multi-scale computational models combining biochemical signaling cascades and multi-compartmental neuron models. PMID:29467627

Production of jet fuel precursor monoterpenoids from engineered Escherichia coli: Production of Jet Fuel Precursor Monoterpenoids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mendez-Perez, Daniel; Alonso-Gutierrez, Jorge; Hu, Qijun

Monoterpenes (C 10 isoprenoids) are the main components of essential oils and are possible precursors for many commodity chemicals and high energy density fuels. Monoterpenes are synthesized from geranyl diphosphate (GPP), which is also the precursor for the biosynthesis of farnesyl diphosphate (FPP). FPP biosynthesis diverts the carbon flux from monoterpene production to C 15 products and quinone biosynthesis. In this study, we tested a chromosomal mutation of Escherichia coli's native FPP synthase (IspA) to improve GPP availability for the production of monoterpenes using a heterologous mevalonate pathway. Monoterpene production at high levels required not only optimization of GPP productionmore » but also a basal level of FPP to maintain growth. The optimized strains produced two jet fuel precursor monoterpenoids 1,8-cineole and linalool at the titer of 653 mg/L and 505 mg/L, respectively, in batch cultures with 1% glucose. The engineered strains developed in this work provide useful resources for the production of high-value monoterpenes.« less

Production of jet fuel precursor monoterpenoids from engineered Escherichia coli: Production of Jet Fuel Precursor Monoterpenoids

DOE PAGES

Mendez-Perez, Daniel; Alonso-Gutierrez, Jorge; Hu, Qijun; ...

2017-05-18

Monoterpenes (C 10 isoprenoids) are the main components of essential oils and are possible precursors for many commodity chemicals and high energy density fuels. Monoterpenes are synthesized from geranyl diphosphate (GPP), which is also the precursor for the biosynthesis of farnesyl diphosphate (FPP). FPP biosynthesis diverts the carbon flux from monoterpene production to C 15 products and quinone biosynthesis. In this study, we tested a chromosomal mutation of Escherichia coli's native FPP synthase (IspA) to improve GPP availability for the production of monoterpenes using a heterologous mevalonate pathway. Monoterpene production at high levels required not only optimization of GPP productionmore » but also a basal level of FPP to maintain growth. The optimized strains produced two jet fuel precursor monoterpenoids 1,8-cineole and linalool at the titer of 653 mg/L and 505 mg/L, respectively, in batch cultures with 1% glucose. The engineered strains developed in this work provide useful resources for the production of high-value monoterpenes.« less

Alterations in neuronal activity in basal ganglia-thalamocortical circuits in the parkinsonian state

PubMed Central

Galvan, Adriana; Devergnas, Annaelle; Wichmann, Thomas

2015-01-01

In patients with Parkinson’s disease and in animal models of this disorder, neurons in the basal ganglia and related regions in thalamus and cortex show changes that can be recorded by using electrophysiologic single-cell recording techniques, including altered firing rates and patterns, pathologic oscillatory activity and increased inter-neuronal synchronization. In addition, changes in synaptic potentials or in the joint spiking activities of populations of neurons can be monitored as alterations in local field potentials (LFPs), electroencephalograms (EEGs) or electrocorticograms (ECoGs). Most of the mentioned electrophysiologic changes are probably related to the degeneration of diencephalic dopaminergic neurons, leading to dopamine loss in the striatum and other basal ganglia nuclei, although degeneration of non-dopaminergic cell groups may also have a role. The altered electrical activity of the basal ganglia and associated nuclei may contribute to some of the motor signs of the disease. We here review the current knowledge of the electrophysiologic changes at the single cell level, the level of local populations of neural elements, and the level of the entire basal ganglia-thalamocortical network in parkinsonism, and discuss the possible use of this information to optimize treatment approaches to Parkinson’s disease, such as deep brain stimulation (DBS) therapy. PMID:25698937

miR-25/93 mediates hypoxia-induced immunosuppression by repressing cGAS.

PubMed

Wu, Min-Zu; Cheng, Wei-Chung; Chen, Su-Feng; Nieh, Shin; O'Connor, Carolyn; Liu, Chia-Lin; Tsai, Wen-Wei; Wu, Cheng-Jang; Martin, Lorena; Lin, Yaoh-Shiang; Wu, Kou-Juey; Lu, Li-Fan; Izpisua Belmonte, Juan Carlos

2017-10-01

The mechanisms by which hypoxic tumours evade immunological pressure and anti-tumour immunity remain elusive. Here, we report that two hypoxia-responsive microRNAs, miR-25 and miR-93, are important for establishing an immunosuppressive tumour microenvironment by downregulating expression of the DNA sensor cGAS. Mechanistically, miR-25/93 targets NCOA3, an epigenetic factor that maintains basal levels of cGAS expression, leading to repression of cGAS during hypoxia. This allows hypoxic tumour cells to escape immunological responses induced by damage-associated molecular pattern molecules, specifically the release of mitochondrial DNA. Moreover, restoring cGAS expression results in an anti-tumour immune response. Clinically, decreased levels of cGAS are associated with poor prognosis for patients with breast cancer harbouring high levels of miR-25/93. Together, these data suggest that inactivation of the cGAS pathway plays a critical role in tumour progression, and reveal a direct link between hypoxia-responsive miRNAs and adaptive immune responses to the hypoxic tumour microenvironment, thus unveiling potential new therapeutic strategies.

miR25/93 mediates hypoxia-induced immunosuppression by repressing cGAS

PubMed Central

Wu, Min-Zu; Cheng, Wei-Chung; Chen, Su-Feng; Nieh, Shin; O’Connor, Carolyn; Liu, Chia-Lin; Tsai, Wen-Wei; Wu, Cheng-Jang; Martin, Lorena; Lin, Yaoh-Shiang; Wu, Kou-Juey; Lu, Li-Fan

2017-01-01

The mechanisms by which hypoxic tumors evade immunological pressure and anti-tumor immunity remain elusive. Here, we report that two hypoxia-responsive microRNAs, miR25 and miR93, are important for establishing an immunosuppressive tumor microenvironment by down-regulating expression of the DNA-sensor cGAS. Mechanistically, miR25/93 targets NCOA3, an epigenetic factor that maintains basal levels of cGAS expression, leading to repression of cGAS upon hypoxia. This allows hypoxic tumor cells to escape immunological responses induced by damage-associated molecular pattern molecules (DAMPs), specifically the release of mtDNA. Moreover, restoring cGAS expression results in an anti-tumor immune response. Clinically, decreased levels of cGAS are associated with poor prognosis for patients with breast cancer harboring high levels of miR25/93. Together, these data suggest that inactivation of the cGAS pathway plays a critical role in tumor progression, and reveals a direct link between hypoxia-responsive miRNAs and adaptive immune responses to the hypoxic tumor microenvironment, thus unveiling potential new therapeutic strategies. PMID:28920955

Hypothalamic amenorrhea with normal body weight: ACTH, allopregnanolone and cortisol responses to corticotropin-releasing hormone test.

PubMed

Meczekalski, B; Tonetti, A; Monteleone, P; Bernardi, F; Luisi, S; Stomati, M; Luisi, M; Petraglia, F; Genazzani, A R

2000-03-01

Hypothalamic amenorrhea (HA) is a functional disorder caused by disturbances in gonadotropin-releasing hormone (GnRH) pulsatility. The mechanism by which stress alters GnRH release is not well known. Recently, the role of corticotropin-releasing hormone (CRH) and neurosteroids in the pathophysiology of HA has been considered. The aim of the present study was to explore further the role of the hypothalamic-pituitary-adrenal axis in HA. We included 8 patients (aged 23.16+/-1.72 years) suffering from hypothalamic stress-related amenorrhea with normal body weight and 8 age-matched healthy controls in the follicular phase of the menstrual cycle. We measured basal serum levels of FSH, LH, and estradiol and evaluated ACTH, allopregnanolone and cortisol responses to CRH test in both HA patients and healthy women. Serum basal levels of FSH, LH, and estradiol as well as basal levels of allopregnanolone were significantly lower in HA patients than in controls (P<0.001) while basal ACTH and cortisol levels were significantly higher in amenorrheic patients with respect to controls (P<0.001). The response (area under the curve) of ACTH, allopregnanolone and cortisol to CRH was significantly lower in amenorrheic women compared with controls (P<0.001, P<0.05, P<0.05 respectively). In conclusion, women with HA, despite the high ACTH and cortisol levels and, therefore, hypothalamus-pituitary-adrenal axis hyperactivity, are characterized by low allopregnanolone basal levels, deriving from an impairment of both adrenal and ovarian synthesis. The blunted ACTH, allopregnanolone and cortisol responses to CRH indicate that, in hypothalamic amenorrhea, there is a reduced sensitivity and expression of CRH receptor. These results open new perspectives on the role of neurosteroids in the pathogenesis of hypothalamic amenorrhea.

Characterization of a Crabs Claw Gene in basal eudicot species Epimedium sagittatum (Berberidaceae).

PubMed

Sun, Wei; Huang, Wenjun; Li, Zhineng; Lv, Haiyan; Huang, Hongwen; Wang, Ying

2013-01-08

The Crabs Claw (CRC) YABBY gene is required for regulating carpel development in angiosperms and has played an important role in nectary evolution during core eudicot speciation. The function or expression of CRC-like genes has been explored in two basal eudicots, Eschscholzia californica and Aquilegia formosa. To further investigate the function of CRC orthologous genes related to evolution of carpel and nectary development in basal eudicots, a CRC ortholog, EsCRC, was isolated and characterized from Epimedium sagittatum (Sieb. and Zucc.) Maxim. A phylogenetic analysis of EsCRC and previously identified CRC-like genes placed EsCRC within the basal eudicot lineage. Gene expression results suggest that EsCRC is involved in the development of sepals and carpels, but not nectaries. Phenotypic complementation of the Arabidopsis mutant crc-1 was achieved by constitutive expression of EsCRC. In addition, over-expression of EsCRC in Arabidopsis and tobacco gave rise to abaxially curled leaves. Transgenic results together with the gene expression analysis suggest that EsCRC may maintain a conserved function in carpel development and also play a novel role related to sepal formation. Absence of EsCRC and ElCRC expression in nectaries further indicates that nectary development in non-core eudicots is unrelated to expression of CRC-like genes.

Characterization of a Crabs Claw Gene in Basal Eudicot Species Epimedium sagittatum (Berberidaceae)

PubMed Central

Sun, Wei; Huang, Wenjun; Li, Zhineng; Lv, Haiyan; Huang, Hongwen; Wang, Ying

2013-01-01

The Crabs Claw (CRC) YABBY gene is required for regulating carpel development in angiosperms and has played an important role in nectary evolution during core eudicot speciation. The function or expression of CRC-like genes has been explored in two basal eudicots, Eschscholzia californica and Aquilegia formosa. To further investigate the function of CRC orthologous genes related to evolution of carpel and nectary development in basal eudicots, a CRC ortholog, EsCRC, was isolated and characterized from Epimedium sagittatum (Sieb. and Zucc.) Maxim. A phylogenetic analysis of EsCRC and previously identified CRC-like genes placed EsCRC within the basal eudicot lineage. Gene expression results suggest that EsCRC is involved in the development of sepals and carpels, but not nectaries. Phenotypic complementation of the Arabidopsis mutant crc-1 was achieved by constitutive expression of EsCRC. In addition, over-expression of EsCRC in Arabidopsis and tobacco gave rise to abaxially curled leaves. Transgenic results together with the gene expression analysis suggest that EsCRC may maintain a conserved function in carpel development and also play a novel role related to sepal formation. Absence of EsCRC and ElCRC expression in nectaries further indicates that nectary development in non-core eudicots is unrelated to expression of CRC-like genes. PMID:23299438

Sonic hedgehog-expressing basal cells are general post-mitotic precursors of functional taste receptor cells

PubMed Central

Miura, Hirohito; Scott, Jennifer K.; Harada, Shuitsu; Barlow, Linda A.

2014-01-01

Background Taste buds contain ~60 elongate cells and several basal cells. Elongate cells comprise three functional taste cell types: I - glial cells, II - bitter/sweet/umami receptor cells, and III - sour detectors. Although taste cells are continuously renewed, lineage relationships among cell types are ill-defined. Basal cells have been proposed as taste bud stem cells, a subset of which express Sonic hedgehog (Shh). However, Shh+ basal cells turnover rapidly suggesting that Shh+ cells are precursors of some or all taste cell types. Results To fate map Shh-expressing cells, mice carrying ShhCreERT2 and a high (CAG-CAT-EGFP) or low (R26RLacZ) efficiency reporter allele were given tamoxifen to activate Cre in Shh+ cells. Using R26RLacZ, lineage-labeled cells occur singly within buds, supporting a post-mitotic state for Shh+ cells. Using either reporter, we show that Shh+ cells differentiate into all three taste cell types, in proportions reflecting cell type ratios in taste buds (I > II > III). Conclusions Shh+ cells are not stem cells, but are post-mitotic, immediate precursors of taste cells. Shh+ cells differentiate into each of the three taste cell types, and the choice of a specific taste cell fate is regulated to maintain the proper ratio within buds. PMID:24590958

Study of adrenal function in patients with tuberculosis.

PubMed

Sarin, Bipan Chander; Sibia, Keerat; Kukreja, Sahiba

2018-07-01

Although subclinical adrenal insufficiency has been documented in tuberculosis but it has been neglected in mainstream management of TB due to inconclusive data on its prevalence in TB. The fact that adrenal insufficiency may result not only in poor general condition of the patient but also sudden death due to adrenal crisis, makes it all the more important to address this issue seriously. In this non-randomized interventional study comprising of 100 cases of TB, our aim was to assess the adreno-cortical functions in patients with pulmonary TB (50 cases) and extra-pulmonary TB (50 cases) in an attempt to determine if there is any compromise of adrenal function. In this study, 100 cases of active TB were investigated for adrenal insufficiency by measuring morning fasting basal serum cortisol levels, followed by low dose ACTH stimulation test using 1μg synacthen (synthetic ACTH analog). The post-stimulation serum cortisol levels were estimated. Basal serum cortisol levels<220nmol/L or post-stimulation test serum cortisol level increment<200nmol/L or post-stimulation serum cortisol levels<500nmol/L were suggestive of adrenal insufficiency. Basal serum cortisol level was low in 16% cases and after low dose ACTH stimulation test, cortisol response was subnormal in 76% cases. Incidence of adrenal insufficiency in pulmonary TB (74%) and extra-pulmonary TB (78%) were comparable. The number of females having adrenal insufficiency in both the groups was higher than the males (67.3% males and 83.3% females) but the difference was statistically significant only in extra-pulmonary TB group (p=0.011). On analysing the data, the sensitivity of basal serum cortisol level estimation in diagnosing adrenal insufficiency was observed to be 21.05% and its specificity was 100%. Positive predictive value was 100% and negative predictive value was 28.57%. Diagnostic accuracy of basal serum cortisol level estimation was observed to be 40%. The incidence of subclinical adrenal insufficiency in TB cases attending chest department at a tertiary care hospital was significantly high but comparable in both pulmonary and extra-pulmonary type of TB. Females in general and particularly those with extra-pulmonary TB were observed to be at increased risk of adrenal insufficiency. The low dose ACTH stimulation test was able to identify cases with adrenal insufficiency which had normal basal serum cortisol levels. Screening all TB cases for adrenal insufficiency by measuring both morning basal serum cortisol levels and low dose ACTH stimulation test can help identify cases at risk of fatal adrenal crisis and institute timely management, thus improving disease prognosis. Copyright © 2017 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

A Comparison of Difficulty Levels of Vocabulary in First Grade Basal Readers for Preschool Dual Language Learners and Monolingual English Learners

ERIC Educational Resources Information Center

Leung, Cynthia B.; Silverman, Rebecca; Nandakumar, Ratna; Qian, Xiaoyu; Hines, Sara

2011-01-01

The present study investigated preschoolers' knowledge of vocabulary that appears in first grade basal readers by applying Rasch modeling to data from a researcher-developed receptive picture vocabulary assessment administered to 238 children. Levels of word difficulty for dual language learners (DLLs) and monolingual English learners (MELs) were…

Multiple isoforms for the catalytic subunit of PKA in the basal fungal lineage Mucor circinelloides.

PubMed

Fernández Núñez, Lucas; Ocampo, Josefina; Gottlieb, Alexandra M; Rossi, Silvia; Moreno, Silvia

2016-12-01

Protein kinase A (PKA) activity is involved in dimorphism of the basal fungal lineage Mucor. From the recently sequenced genome of Mucor circinelloides we could predict ten catalytic subunits of PKA. From sequence alignment and structural prediction we conclude that the catalytic core of the isoforms is conserved, and the difference between them resides in their amino termini. This high number of isoforms is maintained in the subdivision Mucoromycotina. Each paralogue, when compared to the ones form other fungi is more homologous to one of its orthologs than to its paralogs. All of these fungal isoforms cannot be included in the class I or II in which fungal protein kinases have been classified. mRNA levels for each isoform were measured during aerobic and anaerobic growth. The expression of each isoform is differential and associated to a particular growth stage. We reanalyzed the sequence of PKAC (GI 20218944), the only cloned sequence available until now for a catalytic subunit of M. circinelloides. PKAC cannot be classified as a PKA because of its difference in the conserved C-tail; it shares with PKB a conserved C2 domain in the N-terminus. No catalytic activity could be measured for this protein nor predicted bioinformatically. It can thus be classified as a pseudokinase. Its importance can not be underestimated since it is expressed at the mRNA level in different stages of growth, and its deletion is lethal. Copyright © 2016 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Hepatic FcRn regulates albumin homeostasis and susceptibility to liver injury

PubMed Central

Pyzik, Michal; Rath, Timo; Kuo, Timothy T.; Win, Sanda; Baker, Kristi; Hubbard, Jonathan J.; Grenha, Rosa; Gandhi, Amit; Krämer, Thomas D.; Mezo, Adam R.; McDonnell, Kevin; Nienaber, Vicki; Andersen, Jan Terje; Mizoguchi, Atsushi; Blumberg, Laurence; Purohit, Shalaka; Jones, Susan D.; Christianson, Greg; Lencer, Wayne I.; Sandlie, Inger; Kaplowitz, Neil; Roopenian, Derry C.; Blumberg, Richard S.

2017-01-01

The neonatal crystallizable fragment receptor (FcRn) is responsible for maintaining the long half-life and high levels of the two most abundant circulating proteins, albumin and IgG. In the latter case, the protective mechanism derives from FcRn binding to IgG in the weakly acidic environment contained within endosomes of hematopoietic and parenchymal cells, whereupon IgG is diverted from degradation in lysosomes and is recycled. The cellular location and mechanism by which FcRn protects albumin are partially understood. Here we demonstrate that mice with global or liver-specific FcRn deletion exhibit hypoalbuminemia, albumin loss into the bile, and increased albumin levels in the hepatocyte. In vitro models with polarized cells illustrate that FcRn mediates basal recycling and bidirectional transcytosis of albumin and uniquely determines the physiologic release of newly synthesized albumin into the basal milieu. These properties allow hepatic FcRn to mediate albumin delivery and maintenance in the circulation, but they also enhance sensitivity to the albumin-bound hepatotoxin, acetaminophen (APAP). As such, global or liver-specific deletion of FcRn results in resistance to APAP-induced liver injury through increased albumin loss into the bile and increased intracellular albumin scavenging of reactive oxygen species. Further, protection from injury is achieved by pharmacologic blockade of FcRn–albumin interactions with monoclonal antibodies or peptide mimetics, which cause hypoalbuminemia, biliary loss of albumin, and increased intracellular accumulation of albumin in the hepatocyte. Together, these studies demonstrate that the main function of hepatic FcRn is to direct albumin into the circulation, thereby also increasing hepatocyte sensitivity to toxicity. PMID:28330995

FAK Is Required for Schwann Cell Spreading on Immature Basal Lamina to Coordinate the Radial Sorting of Peripheral Axons with Myelination

PubMed Central

Grove, Matthew

2014-01-01

Without Focal Adhesion Kinase (FAK), developing murine Schwann cells (SCs) proliferate poorly, sort axons inefficiently, and cannot myelinate peripheral nerves. Here we show that FAK is required for the development of SCs when their basal lamina (BL) is fragmentary, but not when it is mature in vivo. Mutant SCs fail to spread on fragmentary BL during development in vivo, and this is phenocopied by SCs lacking functional FAK on low laminin (LN) in vitro. Furthermore, SCs without functional FAK initiate differentiation prematurely, both in vivo and in vitro. In contrast to their behavior on high levels of LN, SCs lacking functional FAK grown on low LN display reduced spreading, proliferation, and indicators of contractility (i.e., stress fibers, arcs, and focal adhesions) and are primed to differentiate. Growth of SCs lacking functional FAK on increasing LN concentrations in vitro revealed that differentiation is not regulated by G1 arrest but rather by cell spreading and the level of contractile actomyosin. The importance of FAK as a critical regulator of the specific response of developing SCs to fragmentary BL was supported by the ability of adult FAK mutant SCs to remyelinate demyelinated adult nerves on mature BL in vivo. We conclude that FAK promotes the spreading and actomyosin contractility of immature SCs on fragmentary BL, thus maintaining their proliferation, and preventing differentiation until they reach high density, thereby promoting radial sorting. Hence, FAK has a critical role in the response of SCs to limiting BL by promoting proliferation and preventing premature SC differentiation. PMID:25274820

Personalized intensification of insulin therapy in type 2 diabetes - does a basal-bolus regimen suit all patients?

PubMed

Giugliano, D; Sieradzki, J; Stefanski, A; Gentilella, R

2016-08-01

Many patients with type 2 diabetes mellitus (T2DM) require insulin therapy. If basal insulin fails to achieve glycemic control, insulin intensification is one possible treatment intensification strategy. We summarized clinical data from randomized clinical trials designed to compare the efficacy and safety of basal-bolus and premixed insulin intensification regimens. We defined a between-group difference of ≥0.3% in end-of-study glycated hemoglobin (HbA1c) as clinically meaningful. A PubMed database search supplemented by author-identified papers yielded 15 trials which met selection criteria: randomized design, patients with T2DM receiving basal-bolus (bolus injection ≤3 times/day) vs. premixed (≤3 injections/day) insulin regimens, primary/major endpoint(s) HbA1c- and/or hypoglycemia-related, and trial duration ≥12 weeks. Glycemic control improved with both basal-bolus and premixed insulin regimens with - in most cases - acceptable levels of weight gain and hypoglycemia. A clinically meaningful difference between regimens in glycemic control was recorded in only four comparisons, all of which favored basal-bolus therapy. The incidence of hypoglycemia was significantly different between regimens in only three comparisons, one of which favored premixed insulin and two basal-bolus therapy. Of the four trials that reported a significant difference between regimens in bodyweight change, two favored basal-bolus therapy and two favored premixed insulin. Thus, on a population level, neither basal-bolus therapy nor premixed insulin showed a consistent advantage in terms of glycemic control, hypoglycemic risk, or bodyweight gain. It is therefore recommended that clinicians should adopt an individualized approach to insulin intensification - taking into account the benefits and risks of each treatment approach and the attitude and preferences of each patient - in the knowledge that both basal-bolus and premixed regimens may be successful.

Origin of Ameloblastoma From Basal Cells of the Oral Epithelium- Establishing the Relation Using Neuroectodermal Markers

PubMed Central

Suneela, S; Narayan, T V; Shreedhar, Balasundari; Mohanty, Leeky; Shenoy, Sadhana; Swaminathan, Uma

2014-01-01

Background and Objectives: Basal cell layer of the oral epithelium has been rightfully regarded as a potential source of odontogenic tumours and cysts, but, without substantial evidence. Also, whether the basal cell layer retains within it, some properties of ectomesenchyme, which was imbibed during the early embryogenesis and hence its neuroectodermal relation, is not known. Here, an attempt is made to establish the hidden neuroectodermal potential of the oral epithelium, especially the basal layer, by observing the expression of known neuroectodermal markers, NSE (Neuron Specific Enolase), Synaptophysin and CD99. The expression of the same markers has also been studied in Ameloblastoma, connecting it with oral epithelium, in turn establishing basal cell layer as a potential source of Ameloblastoma. Materials and Methods: Sections of formalin fixed, paraffin embedded tissue samples of 20 cases of Ameloblastoma and 10 cases of Normal Retromolar mucosa, were stained immunohistochemically with NSE, Synaptophysin, CD99 and also with CK-19 and evaluated for positive expression. Results: Positive reaction was obtained in all the cases of Ameloblastoma and NRM (Normal Retromolar mucosa) with NSE, all the cases of Ameloblastoma and eight cases of NRM with Synaptophysin and in six cases of Ameloblastoma and NRM with CD99. The staining was diffuse and more marked in case of NSE than Synaptophysin and CD99. CK19 staining done to assure that the tissue antigenicity was maintained was positive in all the samples. Interpretation and Conclusion: A strong relationship between the neuroectoderm, Ameloblastoma and the basal layer of the oral epithelium is established by the study. It favours the hypothesis that the basal cell layer of oral mucosa may be the sought out culprit in most cases of the Ameloblastomas, especially those occurring in the non-tooth bearing area. This would call for the need to incorporate additional therapy in the form of mucosal striping along with the conventional treatment. PMID:25478446

Children's externalizing and internalizing symptoms over time: the role of individual differences in patterns of RSA responding.

PubMed

Hinnant, James Benjamin; El-Sheikh, Mona

2009-11-01

We examined associations between basal respiratory sinus arrhythmia (RSA) in conjunction with RSA regulation with the hypothesis that their interaction would explain unique variability in children's prospective adjustment 2 years later. Participants were 176 children (98 girls; 78 boys) in middle childhood. RSA regulation was assessed through social and problem-solving challenges. Parents reported on children's internalizing and externalizing symptoms. Interactions between RSA baseline and regulation to the social stressor predicted children's later internalizing symptoms. Interactions between RSA baseline and responding to the problem-solving stressor predicted children's externalizing symptoms. The highest levels of internalizing symptoms were predicted for children with both lower basal RSA and higher RSA suppression. The highest levels of externalizing symptoms were predicted for children who demonstrated lower basal RSA in conjunction with RSA augmentation. Findings highlight the importance of the contemporaneous consideration of basal RSA and RSA regulation in the prediction of developmental psychopathology symptomology.

Detection of basal acetylcholine release in the microdialysis of rat frontal cortex by high-performance liquid chromatography using a horseradish peroxidase-osmium redox polymer electrode with pre-enzyme reactor.

PubMed

Kato, T; Liu, J K; Yamamoto, K; Osborne, P G; Niwa, O

1996-06-28

To determine the basal acetylcholine level in the dialysate of rat frontal cortex, a horseradish peroxidase-osmium redox polymer-modified glassy carbon electrode (HRP-GCE) was employed instead of the conventional platinum electrode used in high-performance liquid chromatography-electrochemical detection (HPLC-ED). In initial experiments, an oxidizable unknown compound interfered with the detection of basal acetylcholine release on HPLC-HRP-GCE. An immobilized peroxidase-choline oxidase precolumn (pre-reactor) was included in the HPLC system, to eliminate the interference from the unknown compound. This combination could detect less than 10 fmol of standard acetylcholine and basal acetylcholine levels in the dialysate from a conventional concentric design microdialysis probe, without the use of cholinesterase inhibitor, and may facilitate physiological investigation of cholinergic neuronal activity in the central nervous system.

Effect of basal ganglia injury on central dopamine activity in Gulf War syndrome: correlation of proton magnetic resonance spectroscopy and plasma homovanillic acid levels.

PubMed

Haley, R W; Fleckenstein, J L; Marshall, W W; McDonald, G G; Kramer, G L; Petty, F

2000-09-01

Many complaints of Gulf War veterans are compatible with a neurologic illness involving the basal ganglia. In 12 veterans with Haley Gulf War syndrome 2 and in 15 healthy control veterans of similar age, sex, and educational level, we assessed functioning neuronal mass in both basal ganglia by measuring the ratio of N-acetyl-aspartate to creatine with proton magnetic resonance spectroscopy. Central dopamine activity was assessed by measuring the ratio of plasma homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenlyglycol (MHPG). The logarithm of the age-standardized HVA/MHPG ratio was inversely associated with functioning neuronal mass in the left basal ganglia (R(2) = 0.56; F(1,27) = 33.82; P<.001) but not with that in the right (R(2) = 0. 04; F(1,26) = 1.09; P =.30). Controlling for age, renal clearances of creatinine and weak organic anions, handedness, and smoking did not substantially alter the associations. The reduction in functioning neuronal mass in the left basal ganglia of these veterans with Gulf War syndrome seems to have altered central dopamine production in a lateralized pattern. This finding supports the theory that Gulf War syndrome is a neurologic illness, in part related to injury to dopaminergic neurons in the basal ganglia.

On the Origin of Tremor in Parkinson’s Disease

PubMed Central

Dovzhenok, Andrey; Rubchinsky, Leonid L.

2012-01-01

The exact origin of tremor in Parkinson’s disease remains unknown. We explain why the existing data converge on the basal ganglia-thalamo-cortical loop as a tremor generator and consider a conductance-based model of subthalamo-pallidal circuits embedded into a simplified representation of the basal ganglia-thalamo-cortical circuit to investigate the dynamics of this loop. We show how variation of the strength of dopamine-modulated connections in the basal ganglia-thalamo-cortical loop (representing the decreasing dopamine level in Parkinson’s disease) leads to the occurrence of tremor-like burst firing. These tremor-like oscillations are suppressed when the connections are modulated back to represent a higher dopamine level (as it would be the case in dopaminergic therapy), as well as when the basal ganglia-thalamo-cortical loop is broken (as would be the case for ablative anti-parkinsonian surgeries). Thus, the proposed model provides an explanation for the basal ganglia-thalamo-cortical loop mechanism of tremor generation. The strengthening of the loop leads to tremor oscillations, while the weakening or disconnection of the loop suppresses them. The loop origin of parkinsonian tremor also suggests that new tremor-suppression therapies may have anatomical targets in different cortical and subcortical areas as long as they are within the basal ganglia-thalamo-cortical loop. PMID:22848541

External pancreatic secretion after bombesin infusion in man.

PubMed

Basso, N; Giri, S; Improta, G; Lezoche, E; Melchiorri, P; Percoco, M; Speranza, V

1975-12-01

The effect of bombesin on external pancreatic secretion was studied in seven healthy volunteers and intwo patients with a two-thirds gastrectomy and a pancreatic fistula. After bombesin infusion (15 ng/kg/min), gastrin levels were significantly raised in all volunteers, but remained at basal levels in the gastrectomized patients. Bombesin was effective in stimulating pancreatic secretion in all patients. The volume of secretion increased tow-fold when compared with basal volume. Amylase and trypsin concentrations and outputs in the duodenal juice were greatly agumented (amylase concentration: basal, 70 dye U/ml; post-bombesin, 620 dye U/ml. Amylase output: basal, 1000 dye U/15 min; post-bombesin, 15,800 dye U/15 min). Secretin, when administered in conjunction with bombesin, partially inhibited its secretory effect. Bicarbonate secretion was slightly stimulated by bombesin, but at a very low level. A similar pattern of results was obtained in the two gastrectomized patients. In man, bombesin exerts an effect on pancreatic secretion that mimics the effect of CCK-PZ, thus confirming the results obtained in the experimental animal. Gastrin does not play a fundamental role in this phenomenon.

External pancreatic secretion after bombesin infusion in man.

PubMed Central

Basso, N; Giri, S; Improta, G; Lezoche, E; Melchiorri, P; Percoco, M; Speranza, V

1975-01-01

The effect of bombesin on external pancreatic secretion was studied in seven healthy volunteers and intwo patients with a two-thirds gastrectomy and a pancreatic fistula. After bombesin infusion (15 ng/kg/min), gastrin levels were significantly raised in all volunteers, but remained at basal levels in the gastrectomized patients. Bombesin was effective in stimulating pancreatic secretion in all patients. The volume of secretion increased tow-fold when compared with basal volume. Amylase and trypsin concentrations and outputs in the duodenal juice were greatly agumented (amylase concentration: basal, 70 dye U/ml; post-bombesin, 620 dye U/ml. Amylase output: basal, 1000 dye U/15 min; post-bombesin, 15,800 dye U/15 min). Secretin, when administered in conjunction with bombesin, partially inhibited its secretory effect. Bicarbonate secretion was slightly stimulated by bombesin, but at a very low level. A similar pattern of results was obtained in the two gastrectomized patients. In man, bombesin exerts an effect on pancreatic secretion that mimics the effect of CCK-PZ, thus confirming the results obtained in the experimental animal. Gastrin does not play a fundamental role in this phenomenon. PMID:1218823

Parkinson's disease as a system-level disorder.

PubMed

Caligiore, Daniele; Helmich, Rick C; Hallett, Mark; Moustafa, Ahmed A; Timmermann, Lars; Toni, Ivan; Baldassarre, Gianluca

2016-01-01

Traditionally, the basal ganglia have been considered the main brain region implicated in Parkinson's disease. This single area perspective gives a restricted clinical picture and limits therapeutic approaches because it ignores the influence of altered interactions between the basal ganglia and other cerebral components on Parkinsonian symptoms. In particular, the basal ganglia work closely in concert with cortex and cerebellum to support motor and cognitive functions. This article proposes a theoretical framework for understanding Parkinson's disease as caused by the dysfunction of the entire basal ganglia-cortex-cerebellum system rather than by the basal ganglia in isolation. In particular, building on recent evidence, we propose that the three key symptoms of tremor, freezing, and impairments in action sequencing may be explained by considering partially overlapping neural circuits including basal ganglia, cortical and cerebellar areas. Studying the involvement of this system in Parkinson's disease is a crucial step for devising innovative therapeutic approaches targeting it rather than only the basal ganglia. Possible future therapies based on this different view of the disease are discussed.

Hydraulic conductance and the maintenance of water balance in flowers.

PubMed

Roddy, Adam B; Brodersen, Craig R; Dawson, Todd E

2016-10-01

Flowers face desiccating conditions, yet little is known about their ability to transport water. We quantified variability in floral hydraulic conductance (Kflower ) for 20 species from 10 families and related it to traits hypothesized to be associated with liquid and vapour phase water transport. Basal angiosperm flowers had trait values associated with higher water and carbon costs than monocot and eudicot flowers. Kflower was coordinated with water supply (vein length per area, VLA) and loss (minimum epidermal conductance, gmin ) traits among the magnoliids, but was insensitive to variation in these traits among the monocots and eudicots. Phylogenetic independent contrast (PIC) correlations revealed that few traits had undergone coordinated evolution. However, VLA and the desiccation time (Tdes ), the quotient of water content and gmin , had significant trait and PIC correlations. The near absence of stomata from monocot and eudicot flowers may have been critical in minimizing water loss rates among these clades. Early divergent, basal angiosperm flowers maintain higher Kflower because of traits associated with high rates water loss and water supply, while monocot and eudicot flowers employ a more conservative strategy of limiting water loss and may rely on stored water to maintain turgor and delay desiccation. © 2016 John Wiley & Sons Ltd.

Effect of dietary vitamin C on the growth performance and innate immunity of juvenile cobia (Rachycentron canadum).

PubMed

Zhou, Qicun; Wang, Ligai; Wang, Hualang; Xie, Fengjun; Wang, Tuo

2012-06-01

This study was conducted to evaluate the effects of dietary vitamin C on growth performance, hematologic parameters and innate immune responses in juvenile cobia, Rachycentron canadum. Seven practical diets were formulated to contain 0.0 (as the basal diet), 13.6, 27.2, 54.4, 96.6, 193.4 and 386.5 mg ascorbic acid equivalent kg(-1) diet. Each diet was fed to triplicate groups of juvenile cobia with initial body weight of 5.5 g in 500-L cylindrical fiberglass tank. The results of 8 weeks feeding trial showed that typical vitamin C-deficient signs such as spinal deformation and body nigrescence were observed in the fish fed the basal diet. Fish fed the basal diet had significantly lower weight gain, specific growth rate (SGR), protein efficiency ratio (PER) and feed efficiency (FE) than those fed the diets supplemented with vitamin C, but no significant differences were observed among diets supplemented with vitamin C. However, survival rate was significantly affected by the dietary vitamin C levels, fish fed the basal diet had lower survival rate than those fed the diets supplemented with vitamin C. The ascorbic acid concentration in liver was correlated positively with the dietary vitamin C levels, however, the thiobarbituric acid reactive substances (TBARS) concentrations in liver was not significantly affected by the dietary vitamin C levels, although, fish fed the basal diet had the highest TBARS values among all treatments. The activities of serum lysozyme, superoxide dismutase (SOD), alkaline phophatase (AKP) and total immunoglobulin (Ig) were significantly influenced by the dietary vitamin C levels, fish fed the basal diet had lower lysozyme, SOD, AKP and total Ig than those fed diets supplemented with vitamin C. The serum glucose and triglyceride concentrations were significantly affected by the dietary vitamin C levels. Fish fed the basal diet had lower red blood cell and hemoglobin values than those fed the vitamin C supplemented diets. The challenge experiment with Vibrio harveyi showed that lower cumulative survival was in fish fed the unsupplemented diet, the cumulative survival were significantly increased with increase of the dietary ascorbic acid levels from 13.6 to 96.6 mg kg(-1), while the cumulative survival reached plateau when dietary ascorbic acid levels increased from 96.6 to 386.5 mg kg(-1). These results indicated that dietary vitamin C did significantly influence on growth performance and immune response of juvenile cobia. Copyright © 2012 Elsevier Ltd. All rights reserved.

Ventral tegmental ionotropic glutamate receptor stimulation of nucleus accumbens tonic dopamine efflux blunts hindbrain-evoked phasic neurotransmission: implications for dopamine dysregulation disorders.

PubMed

Tye, S J; Miller, A D; Blaha, C D

2013-11-12

Activation of glutamate receptors within the ventral tegmental area (VTA) stimulates extrasynaptic (basal) dopamine release in terminal regions, including the nucleus accumbens (NAc). Hindbrain inputs from the laterodorsal tegmental nucleus (LDT) are critical for elicitation of phasic VTA dopamine cell activity and consequent transient dopamine release. This study investigated the role of VTA ionotropic glutamate receptor (iGluR) stimulation on both basal and LDT electrical stimulation-evoked dopamine efflux in the NAc using in vivo chronoamperometry and fixed potential amperometry in combination with stearate-graphite paste and carbon fiber electrodes, respectively. Intra-VTA infusion of the iGluR agonists (±)-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA; 1 μg/μl) or N-methyl-d-aspartic acid (NMDA; 2 μg/μl) enhanced basal NAc dopamine efflux. This iGluR-mediated potentiation of basal dopamine efflux was paralleled by an attenuation of LDT-evoked transient NAc dopamine efflux, suggesting that excitation of basal activity effectively inhibited the capacity of hindbrain afferents to elicit transient dopamine efflux. In line with this, post-NMDA infusion of the dopamine D2 autoreceptor (D2R) agonist quinpirole (1 μg/μl; intra-VTA) partially recovered NMDA-mediated attenuation of LDT-evoked NAc dopamine, while concurrently attenuating NMDA-mediated potentiation of basal dopamine efflux. Post-NMDA infusion of quinpirole (1 μg/μl) alone attenuated basal and LDT-evoked dopamine efflux. Taken together, these data reveal that hyperstimulation of basal dopamine transmission can stunt hindbrain burst-like stimulation-evoked dopamine efflux. Inhibitory autoreceptor mechanisms within the VTA help to partially recover the magnitude of phasic dopamine efflux, highlighting the importance of both iGluRs and D2 autoreceptors in maintaining the functional balance of tonic and phasic dopamine neurotransmission. Dysregulation of this balance may have important implications for disorders of dopamine dysregulation such as attention deficit hyperactivity disorder. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Vitamin C deficiency increases basal exploratory activity but decreases scopolamine-induced activity in APP/PSEN1 transgenic mice

PubMed Central

Harrison, F. E.; May, J. M.; McDonald, M. P.

2010-01-01

Vitamin C is a powerful antioxidant and its levels are decreased in Alzheimer's patients. Even sub-clinical vitamin C deficiency could impact disease development. To investigate this principle we crossed APP/PSEN1 transgenic mice with Gulo knockout mice unable to synthesize their own vitamin C. Experimental mice were maintained from 6 weeks of age on standard (0.33 g/L) or reduced (0.099 g/L) levels of vitamin C and then assessed for changes in behavior and neuropathology. APP/PSEN1 mice showed impaired spatial learning in the Barnes maze and water maze that was not further impacted by vitamin C level. However, long-term decreased vitamin C levels led to hyperactivity in transgenic mice, with altered locomotor habituation and increased omission errors in the Barnes maze. Decreased vitamin C also led to increased oxidative stress. Transgenic mice were more susceptible to the activity-enhancing effects of scopolamine and low vitamin C attenuated these effects in both genotypes. These data indicate an interaction between the cholinergic system and vitamin C that could be important given the cholinergic degeneration associated with Alzheimer's disease. PMID:19941887

Three-Dimensional mRNA Measurements Reveal Minimal Regional Heterogeneity in Esophageal Squamous Cell Carcinoma

PubMed Central

Yan, Wusheng; Shih, Joanna; Rodriguez-Canales, Jaime; Tangrea, Michael A.; Player, Audrey; Diao, Lixia; Hu, Nan; Goldstein, Alisa M.; Wang, Jing; Taylor, Philip R.; Lippman, Scott M.; Wistuba, Ignacio I.; Emmert-Buck, Michael R.; Erickson, Heidi S.

2014-01-01

The classic tumor clonal evolution theory postulates that cancers change over time to produce unique molecular subclones within a parent neoplasm, presumably including regional differences in gene expression. More recently, however, this notion has been challenged by studies showing that tumors maintain a relatively stable transcript profile. To examine these competing hypotheses, we microdissected discrete subregions containing approximately 3000 to 8000 cells (500 to 1500 μm in diameter) from ex vivo esophageal squamous cell carcinoma (ESCC) specimens and analyzed transcriptomes throughout three-dimensional tumor space. Overall mRNA profiles were highly similar in all 59 intratumor comparisons, in distinct contrast to the markedly different global expression patterns observed in other dissected cell populations. For example, normal esophageal basal cells contained 1918 and 624 differentially expressed genes at a greater than twofold level (95% confidence level of <5% false positives), compared with normal differentiated esophageal cells and ESCC, respectively. In contrast, intratumor regions had only zero to four gene changes at a greater than twofold level, with most tumor comparisons showing none. The present data indicate that, when analyzed using a standard array-based method at this level of histological resolution, ESCC contains little regional mRNA heterogeneity. PMID:23219752

Comparative study of the chondrogenic potential of human bone marrow stromal cells, neonatal chondrocytes and adult chondrocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saha, Sushmita; Kirkham, Jennifer; NIHR Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, Chapel Allerton Hospital, Leeds LS74SA

2010-10-22

Research highlights: {yields} This study has characterised three different cell types under conditions similar to those used for autologous chondrocyte implantation (ACI) for applications in cartilage repair/regeneration. {yields} Compared for the first time the chondrogenic potential of neonatal chondrocytes with human bone marrow stromal cells (HBMSCs) and adult chondrocytes. {yields} Demonstrated that adult chondrocytes hold greatest potential for use in ACI based on their higher proliferation rates, lower alkaline phosphatise activity and enhanced expression of chondrogenic genes. {yields} Demonstrated the need for chondroinduction as a necessary pre-requisite to efficient chondrogenesis in vitro and, by extrapolation, for cell based therapy (e.g.more » ACI or cartilage tissue engineering). -- Abstract: Cartilage tissue engineering is still a major clinical challenge with optimisation of a suitable source of cells for cartilage repair/regeneration not yet fully addressed. The aims of this study were to compare and contrast the differences in chondrogenic behaviour between human bone marrow stromal cells (HBMSCs), human neonatal and adult chondrocytes to further our understanding of chondroinduction relative to cell maturity and to identify factors that promote chondrogenesis and maintain functional homoeostasis. Cells were cultured in monolayer in either chondrogenic or basal medium, recapitulating procedures used in existing clinical procedures for cell-based therapies. Cell doubling time, morphology and alkaline phosphatase specific activity (ALPSA) were determined at different time points. Expression of chondrogenic markers (SOX9, ACAN and COL2A1) was compared via real time polymerase chain reaction. Amongst the three cell types studied, HBMSCs had the highest ALPSA in basal culture and lowest ALPSA in chondrogenic media. Neonatal chondrocytes were the most proliferative and adult chondrocytes had the lowest ALPSA in basal media. Gene expression analysis revealed a difference in the temporal expression of chondrogenic markers which were up regulated in chondrogenic medium compared to levels in basal medium. Of the three cell types studied, adult chondrocytes offer a more promising cell source for cartilage tissue engineering. This comparative study revealed differences between the microenvironment of all three cell types and provides useful information to inform cell-based therapies for cartilage regeneration.« less

Partial hepatic resistance to IL-6-induced inflammation develops in type 2 diabetic mice, while the anti-inflammatory effect of AMPK is maintained.

PubMed

Cansby, Emmelie; Nerstedt, Annika; Amrutkar, Manoj; Durán, Esther Nuñez; Smith, Ulf; Mahlapuu, Margit

2014-08-05

Interleukin-6 (IL-6) induces hepatic inflammation and insulin resistance, and therapeutic strategies to counteract the IL-6 action in liver are of high interest. In this study, we demonstrate that acute treatment with AMP-activated protein kinase (AMPK) agonists AICAR and metformin efficiently repressed IL-6-induced hepatic proinflammatory gene expression and activation of STAT3 in a mouse model of diet-induced type 2 diabetes, bringing it back to basal nonstimulated level. Surprisingly, the inflammatory response in liver induced by IL-6 administration in vivo was markedly blunted in the mice fed a high-fat diet, compared to lean chow-fed controls, while this difference was not replicated in vitro in primary hepatocytes derived from these two groups of mice. In summary, our work reveals that partial hepatic IL-6 resistance develops in the mouse model of type 2 diabetes, while the anti-inflammatory action of AMPK is maintained. Systemic factors, rather than differences in intracellular IL-6 receptor signaling, are likely mediating the relative impairment in IL-6 effect. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Effects of dietary quality on basal metabolic rate and internal morphology of European starlings (Sturnus vulgaris)

USGS Publications Warehouse

Geluso, Keith; Hayes, J.P.

1999-01-01

European starlings (Sturnus vulgaris) were fed either a low- or high-quality diet to test the effects of dietary quality on basal metabolic rate (BMR) and internal morphology. Basal metabolic rate did not differ significantly between the two dietary groups, but internal morphology differed greatly. Starlings fed the low-quality diet had heavier gastrointestinal tracts, gizzards, and livers. Starlings fed the high-quality diet had heavier breast muscles. Starlings on the low-quality diet maintained mass, while starlings on the high-quality diet gained mass. Dry matter digestibility and energy digestibility were lower for starlings fed the low-quality diet, and their food and water intake were greater than starlings on the high-quality diet. The lack of dietary effect on BMR may be the result of increased energy expenditure of digestive organs paralleling a reduction of energy expenditure of organs and tissues not related to digestion (i.e., skeletal muscle). This trade-off in energy allocation among organs suggests a mechanism by which organisms may alter BMR in response to a change in seasonal variation in food availability.

Hydration behavior at the ice-binding surface of the Tenebrio molitor antifreeze protein.

PubMed

Midya, Uday Sankar; Bandyopadhyay, Sanjoy

2014-05-08

Molecular dynamics (MD) simulations have been carried out at two different temperatures (300 and 220 K) to study the conformational rigidity of the hyperactive Tenebrio molitor antifreeze protein (TmAFP) in aqueous medium and the structural arrangements of water molecules hydrating its surface. It is found that irrespective of the temperature the ice-binding surface (IBS) of the protein is relatively more rigid than its nonice-binding surface (NIBS). The presence of a set of regularly arranged internally bound water molecules is found to play an important role in maintaining the flat rigid nature of the IBS. Importantly, the calculations reveal that the strategically located hydroxyl oxygens of the threonine (Thr) residues in the IBS influence the arrangements of five sets of ordered waters around it on two parallel planes that closely resemble the basal plane of ice. As a result, these waters can register well with the ice basal plane, thereby allowing the IBS to preferentially bind at the ice interface and inhibit its growth. This provides a possible molecular reason behind the ice-binding activity of TmAFP at the basal plane of ice.

Dysfunctions of the basal ganglia-cerebellar-thalamo-cortical system produce motor tics in Tourette syndrome

PubMed Central

Arbib, Michael A.; Baldassarre, Gianluca

2017-01-01

Motor tics are a cardinal feature of Tourette syndrome and are traditionally associated with an excess of striatal dopamine in the basal ganglia. Recent evidence increasingly supports a more articulated view where cerebellum and cortex, working closely in concert with basal ganglia, are also involved in tic production. Building on such evidence, this article proposes a computational model of the basal ganglia-cerebellar-thalamo-cortical system to study how motor tics are generated in Tourette syndrome. In particular, the model: (i) reproduces the main results of recent experiments about the involvement of the basal ganglia-cerebellar-thalamo-cortical system in tic generation; (ii) suggests an explanation of the system-level mechanisms underlying motor tic production: in this respect, the model predicts that the interplay between dopaminergic signal and cortical activity contributes to triggering the tic event and that the recently discovered basal ganglia-cerebellar anatomical pathway may support the involvement of the cerebellum in tic production; (iii) furnishes predictions on the amount of tics generated when striatal dopamine increases and when the cortex is externally stimulated. These predictions could be important in identifying new brain target areas for future therapies. Finally, the model represents the first computational attempt to study the role of the recently discovered basal ganglia-cerebellar anatomical links. Studying this non-cortex-mediated basal ganglia-cerebellar interaction could radically change our perspective about how these areas interact with each other and with the cortex. Overall, the model also shows the utility of casting Tourette syndrome within a system-level perspective rather than viewing it as related to the dysfunction of a single brain area. PMID:28358814

Dysfunctions of the basal ganglia-cerebellar-thalamo-cortical system produce motor tics in Tourette syndrome.

PubMed

Caligiore, Daniele; Mannella, Francesco; Arbib, Michael A; Baldassarre, Gianluca

2017-03-01

Motor tics are a cardinal feature of Tourette syndrome and are traditionally associated with an excess of striatal dopamine in the basal ganglia. Recent evidence increasingly supports a more articulated view where cerebellum and cortex, working closely in concert with basal ganglia, are also involved in tic production. Building on such evidence, this article proposes a computational model of the basal ganglia-cerebellar-thalamo-cortical system to study how motor tics are generated in Tourette syndrome. In particular, the model: (i) reproduces the main results of recent experiments about the involvement of the basal ganglia-cerebellar-thalamo-cortical system in tic generation; (ii) suggests an explanation of the system-level mechanisms underlying motor tic production: in this respect, the model predicts that the interplay between dopaminergic signal and cortical activity contributes to triggering the tic event and that the recently discovered basal ganglia-cerebellar anatomical pathway may support the involvement of the cerebellum in tic production; (iii) furnishes predictions on the amount of tics generated when striatal dopamine increases and when the cortex is externally stimulated. These predictions could be important in identifying new brain target areas for future therapies. Finally, the model represents the first computational attempt to study the role of the recently discovered basal ganglia-cerebellar anatomical links. Studying this non-cortex-mediated basal ganglia-cerebellar interaction could radically change our perspective about how these areas interact with each other and with the cortex. Overall, the model also shows the utility of casting Tourette syndrome within a system-level perspective rather than viewing it as related to the dysfunction of a single brain area.

Fine root biomass in relation to site and stand characteristics in Norway spruce and Scots pine stands.

PubMed

Helmisaari, Heljä-Sisko; Derome, John; Nöjd, Pekka; Kukkola, Mikko

2007-10-01

Variations in fine root biomass of trees and understory in 16 stands throughout Finland were examined and relationships to site and stand characteristics determined. Norway spruce fine root biomass varied between 184 and 370 g m(-2), and that of Scots pine ranged between 149 and 386 g m(-2). In northern Finland, understory roots and rhizomes (< 2 mm diameter) accounted for up to 50% of the stand total fine root biomass. Therefore, the fine root biomass of trees plus understory was larger in northern Finland in stands of both tree species, resulting in a negative relationship between fine root biomass and the temperature sum and a positive relationship between fine root biomass and the carbon:nitrogen ratio of the soil organic layer. The foliage:fine root ratio varied between 2.1 and 6.4 for Norway spruce and between 0.8 and 2.2 for Scots pine. The ratio decreased for both Norway spruce and Scots pine from south to north, as well as from fertile to more infertile site types. The foliage:fine root ratio of Norway spruce was related to basal area and stem surface area. The strong positive correlations of these three parameters with fine root nitrogen concentration implies that more fine roots are needed to maintain a certain amount of foliage when nutrient availability is low. No significant relationships were found between stand parameters and fine root biomass at the stand level, but the relationships considerably improved when both fine root biomass and stand parameters were calculated for the mean tree in the stand. When the northern and southern sites were analyzed separately, fine root biomass per tree of both species was significantly correlated with basal area and stem surface area per tree. Basal area, stem surface area and stand density can be estimated accurately and easily. Thus, our results may have value in predicting fine root biomass at the tree and stand level in boreal Norway spruce and Scots pine forests.

K(+)- and temperature-evoked taurine efflux from hypothalamic astrocytes.

PubMed

Tigges, G A; Philibert, R A; Dutton, G R

1990-10-30

Hypothalamic astrocytes in culture released taurine, a suspected inhibitory amino acid neurotransmitter/neuromodulator/osmoregulator, in response to isoosmotically increasing extracellular K+ in a dose-dependent fashion. In the absence of added Ca2+, basal release levels rose to approach those obtained after exposure to 60 mM K+ in the presence of 2.5 mM Ca2+, and were only partially lowered by the addition of 10 mM Mg2+. Stimulation with K+ (60 mM) did not further increase taurine efflux above the high basal levels seen in the absence of Ca2+. Under standard conditions complete replacement of Na+ with choline Cl had little effect on basal taurine release, but reduced K(+)-evoked (60 mM) efflux by 60%. The temperature dependence of the basal levels of taurine released from hypothalamic astrocytes was similar to that seen for cultured cerebellar astrocytes and neurons over the range 5-50 degrees C. Taurine release increased from 5 to 15 degrees C, remained constant between 15 and 33 degrees C, decreased between 33 and 37 degrees C and increased thereafter. The infection point of increased basal taurine release seen around 37 degrees C (most prominent in astrocytes), may be of physiological significance. Results presented also show that the ion (Na+, Ca2+ and K+) sensitivities of taurine efflux for cultured hypothalamic astrocytes are similar to those previously reported for cultured astrocytes from the cerebellum.

Basal and dynamic relationships between implicit power motivation and estradiol in women.

PubMed

Stanton, Steven J; Schultheiss, Oliver C

2007-12-01

This study investigated basal and reciprocal relationships between implicit power motivation (n Power), a preference for having impact and dominance over others, and both salivary estradiol and testosterone in women. 49 participants completed the Picture Story Exercise, a measure of n Power. During a laboratory contest, participants competed in pairs on a cognitive task and contest outcome (win vs. loss) was experimentally varied. Estradiol and testosterone levels were determined in saliva samples collected at baseline and several times post-contest, including 1 day post-contest. n Power was positively associated with basal estradiol concentrations. The positive correlation between n Power and basal estradiol was stronger in single women, women not taking oral contraceptives, or in women with low-CV estradiol samples than in the overall sample of women. Women's estradiol responses to a dominance contest were influenced by the interaction of n Power and contest outcome: estradiol increased in power-motivated winners but decreased in power-motivated losers. For power-motivated winners, elevated levels of estradiol were still present the day after the contest. Lastly, n Power and estradiol did not correlate with self-reported dominance and correlated negatively with self-reported aggression. Self-reported dominance and aggression did not predict estradiol changes as a function of contest outcome. Overall, n Power did not predict basal testosterone levels or testosterone changes as a function of dominance contest outcome.

Testosterone-induced increase of insulin-like growth factor I levels depends upon normal levels of growth hormone.

PubMed

Saggese, G; Cesaretti, G; Franchi, G; Startari, L

1996-08-01

Pubertal development is associated with a rise in plasma insulin-like growth factor I (IGF-I) levels that is related both to the increase in sex steroids and/or to the sex steroid-induced augmentation in endogenous growth hormone (GH) secretion. In order to investigate the relationship between IGF-I, GH and testosterone, we examined 42 male subjects with various clinical conditions (classical GH deficiency (CGHD, N = 5), non-classical GH deficiency (NCGHD, N = 7), short idiopathic stature (N = 6), nutritional obesity (N = 8), GH-treated CGHD (N = 4), GH-treated NCGHD (N = 5) and normal stature (N = 7)) in which , for evaluation of hypogonadism (i.e. the absence of one or both testes from the scrotal sac), human chorionic gonadotropin (hCG) tests were performed. We measured IGF-I, total and free testosterone and dehydroepiandrosterone sulfate (DHEAS) by radioimmunoassays before and 48 and 96 h after the start of the test. The values of IGF-I were lower (0.001 < p < 0.005) in CGHD and NCGHD than in the other groups. In comparison to basal levels, IGF-I values increased (0.005 < p < 0.05) both 48 and 96 h after the start of the hCG test in short idiopathic and normal stature children and in GH-treated subjects with NCGHD, but only 96 h in subjects with untreated NCGHD and GH-treated CGHD. No difference was demonstrated in basal values of total testosterone among any of the groups, while basal free testosterone levels were higher (0.001 < p < 0.05) in GH-treated subjects with NCGHD than in all the other groups except nutritional obesity; furthermore, free testosterone was higher (p < 0.05) in nutritional obesity than in CGHD. The values of total and free testosterone obtained both 48 and 96 h after the start of the hCG test were higher (0.001 < p < 0.05) than basal values in all groups. The DHEAS values did not show any significant change during the hCG test. Basal values were higher (0.01 < p < 0.05) in nutritional obesity than in the other groups. Considering all groups, chronological age, bone age and bone age/chronological age ratio were correlated with basal free testosterone, IGF-I and DHEAS levels (0.001 < p < 0.05), while basal free testosterone and IGF-I values were correlated with DHEAS levels (p < 0.005 and < 0.01, respectively). In conclusion, our study during the hCG test in boys with various clinical conditions demonstrated an increase in IGF-I concentrations only in those boys with sufficient GH secretion or GH replacement therapy. These findings indicate that both sex steroids and GH are necessary to allow for the pubertal increase in IGF-I levels.

MEAT SCIENCE AND MUSCLE BIOLOGY SYMPOSIUM

PubMed Central

Bi, P.; Kuang, S.

2012-01-01

Stem cell niche plays a critical role in regulating the behavior and function of adult stem cells that underlie tissue growth, maintenance, and regeneration. In the skeletal muscle, stem cells, called satellite cells, contribute to postnatal muscle growth and hypertrophy, and thus, meat production in agricultural animals. Satellite cells are located adjacent to mature muscle fibers underneath a sheath of basal lamina. Microenvironmental signals from extracellular matrix mediated by the basal lamina and from the host myofiber both impinge on satellite cells to regulate their activity. Furthermore, several types of muscle interstitial cells, including intramuscular preadipocytes and connective tissue fibroblasts, have recently been shown to interact with satellite cells and actively regulate the growth and regeneration of postnatal skeletal muscles. From this regard, interstitial adipogenic cells are not only important for marbling and meat quality, but also represent an additional cellular component of the satellite cell niche. At the molecular level, these interstitial cells may interact with satellite cells through cell surface ligands, such as delta-like 1 homolog (Dlk1) protein whose overexpression is thought to be responsible for muscle hypertrophy in callipyge sheep. In fact, extracellular Dlk1 protein has been shown to promote the myogenic differentiation of satellite cells. Understanding the cellular and molecular mechanisms within the stem cell niche that regulate satellite cell differentiation and maintain muscle homeostasis may lead to promising approaches to optimizing muscle growth and composition, thus improving meat production and quality. PMID:22100594

Interindividual differences in stress sensitivity: basal and stress-induced cortisol levels differentially predict neural vigilance processing under stress

PubMed Central

Klumpers, Floris; Everaerd, Daphne; Kooijman, Sabine C.; van Wingen, Guido A.; Fernández, Guillén

2016-01-01

Stress exposure is known to precipitate psychological disorders. However, large differences exist in how individuals respond to stressful situations. A major marker for stress sensitivity is hypothalamus–pituitary–adrenal (HPA)-axis function. Here, we studied how interindividual variance in both basal cortisol levels and stress-induced cortisol responses predicts differences in neural vigilance processing during stress exposure. Implementing a randomized, counterbalanced, crossover design, 120 healthy male participants were exposed to a stress-induction and control procedure, followed by an emotional perception task (viewing fearful and happy faces) during fMRI scanning. Stress sensitivity was assessed using physiological (salivary cortisol levels) and psychological measures (trait questionnaires). High stress-induced cortisol responses were associated with increased stress sensitivity as assessed by psychological questionnaires, a stronger stress-induced increase in medial temporal activity and greater differential amygdala responses to fearful as opposed to happy faces under control conditions. In contrast, high basal cortisol levels were related to relative stress resilience as reflected by higher extraversion scores, a lower stress-induced increase in amygdala activity and enhanced differential processing of fearful compared with happy faces under stress. These findings seem to reflect a critical role for HPA-axis signaling in stress coping; higher basal levels indicate stress resilience, whereas higher cortisol responsivity to stress might facilitate recovery in those individuals prone to react sensitively to stress. PMID:26668010

Basal levels and GnRH-induced responses of peripheral testosterone and estrogen in Holstein bulls with poor semen quality.

PubMed

Devkota, Bhuminand; Takahashi, Ken-Ichi; Matsuzaki, Shigenori; Matsui, Motozumi; Miyamoto, Akio; Yamagishi, Norio; Osawa, Takeshi; Hashizume, Tsutomu; Izaike, Yoshiaki; Miyake, Yoh-Ichi

2011-06-01

The present study investigated the basal levels and GnRH-induced responses of peripheral testosterone and estrogen in Holstein bulls with poor semen quality. On the basis of semen parameters, bulls (n=5) having poor semen quality were selected as experimental bulls, and good semen quality bulls (n=4) were used as control bulls. Both groups were treated intramuscularly once with GnRH (250 µg of fertirelin acetate). Blood samples were collected at -1 day (d), -30 min and 0 h (treatment) followed by every 30 min for 5 h and 1, 3 and 5 d post-GnRH treatment (PGT), and LH, testosterone and estradiol-17β (E(2)) concentrations were measured. The pretreatment concentrations were used as basal levels. The percentage increments based on the 0-h levels were calculated per bull for each sampling time until 5 h PGT, and differences were compared between the experimental and control groups. The PGT concentrations of testosterone and basal and PGT concentrations of E(2) were significantly lower in the experimental group. The testosterone increment in the experimental group was delayed and significantly lower from 1 to 5 h PGT than those in the control group. It can be suggested that bulls with poor semen quality have delayed and lower GnRH-induced testosterone response and may also have lower estrogen levels.

Histamine and thrombin modulate endothelial focal adhesion through centripetal and centrifugal forces.

PubMed Central

Moy, A B; Van Engelenhoven, J; Bodmer, J; Kamath, J; Keese, C; Giaever, I; Shasby, S; Shasby, D M

1996-01-01

We examined the contribution of actin-myosin contraction to the modulation of human umbilical vein endothelial cell focal adhesion caused by histamine and thrombin. Focal adhesion was measured as the electrical resistance across a cultured monolayer grown on a microelectrode. Actin-myosin contraction was measured as isometric tension of cultured monolayers grown on a collagen gel. Histamine immediately decreased electrical resistance but returned to basal levels within 3-5 min. Histamine did not increase isometric tension. Thrombin also immediately decreased electrical resistance, but, however, resistance did not return to basal levels for 40-60 min. Thrombin also increased isometric tension, ML-7, an inhibitor of myosin light chain kinase, prevented increases in myosin light chain phosphorylation and increases in tension development in cells exposed to thrombin. ML-7 did not prevent a decline in electrical resistance in cells exposed to thrombin. Instead, ML-7 restored the electrical resistance to basal levels in a shorter period of time (20 min) than cells exposed to thrombin alone. Also, histamine subsequently increased electrical resistance to above basal levels, and thrombin initiated an increase in resistance during the time of peak tension development. Hence, histamine and thrombin modulate endothelial cell focal adhesion through centripetal and centrifugal forces. PMID:8613524

Children's Literature in the Basals.

ERIC Educational Resources Information Center

O'Brien, Maureen A.

Three basal reading series, levels kindergarten through grade three, were studied to categorize the types of literature each contained. The following series were analyzed: "The Headway Program" (Open Court Publishing Company), "Series r Macmillan Reading," and "Basics in Reading" (Scott, Foresman and Company). It was…

Effect of acute hyperglycemia on basal and bombesin-stimulated pancreaticobiliary secretion in humans.

PubMed

Lam, W F; Masclee, A A; Muller, E S; Souverijn, J H; Lamers, C B

1998-08-01

This study was undertaken to investigate the effect of acute hyperglycemia on basal and bombesin-stimulated pancreaticobiliary secretion. Seven healthy subjects participated in two experiments performed in random order during normoglycemia and hyperglycemic clamping at 15 mM. Duodenal outputs of bilirubin, trypsin, amylase, and bicarbonate were measured by aspiration with a recovery marker under basal conditions for 60 min and during continuous infusion of bombesin (1 ng/kg x min) for 60 min. Plasma cholecystokinin (CCK) and pancreatic polypeptide (PP) levels were determined at regular intervals. Compared to normoglycemia, during hyperglycemia basal outputs of bilirubin (17 +/- 3 vs. 0.9 +/- 0.4 micromol/60 min), trypsin (24 +/- 4 vs. 4 +/- 1 U/60 min), amylase (12 +/- 1 vs. 3 +/- 1 kU/60 min), and bicarbonate (2.9 +/- 0.5 vs. 1.2 +/- 0.2 mmol/60 min) were significantly p < 0.05) reduced. Bombesin significantly (p < 0.05) increased pancreaticobiliary output during both normo- and hyperglycemia. During hyperglycemia bombesin-stimulated 60-min outputs of bilirubin, trypsin, amylase, and bicarbonate were not significantly different compared to those during normoglycemia. Basal and bombesin-stimulated plasma PP concentrations were significantly (p < 0.05) reduced during hyperglycemia, but plasma CCK levels were not significantly different. It is concluded that acute hyperglycemia reduces basal but does not affect bombesin-induced pancreaticobiliary secretion.

The difficulty with correlations: Energy expenditure and brain mass in bats.

PubMed

McNab, Brian K; Köhler, Meike

2017-10-01

Brain mass has been suggested to determine a mammal's energy expenditure. This potential dependence is examined in 48 species of bats. A correlation between characters may be direct or derived from shared correlations with intervening factors without a direct interaction. Basal rate of metabolism in these bats increases with brain mass: large brains are more expensive than small brains, and both brain mass and basal rate increase with body mass. Basal rate and brain mass also correlate with food habits in bats. Mass-independent basal rate weakly correlates with mass-independent brain mass, the correlation only accounting for 12% of the variation in basal rate, which disappears when the combined effects of body mass and food habits are deleted. The correlation between basal rate and brain mass seen in this and other studies usually accounts for <10% of the variation in basal rate and often <4%, even when statistically significant, a minimalist explanation for the level the basal rate. This correlation probably reflects the intermediacy of secondary factors, as occurred with food habits in bats. Most biological correlations are complicated and must be examined in detail before assurance can be given as to their bases. Copyright © 2017 Elsevier Inc. All rights reserved.

Fire and vegetation dynamics in the Cross Timbers forests of south-central North America

Treesearch

Steve W. Hallgren; Ryan D. DeSantis; Jesse A. Burton

2012-01-01

The vegetation of the Cross Timbers forests was maintained for thousands of years by fire; the historic fire return interval was likely 1 to 10 years. Fire suppression over the past century led to a doubling of stand basal area, increased diversity of tree species, reduced dominance of oak, and increased mesic species intolerant of fire. Dendrochronological studies...

The longest active thinned and pruned loblolly pine permanent plots: the last measurement

Treesearch

Denise R. General; Curtis L. VanderSchaaf; B. Zeide

2013-01-01

The longest active study of the effects of thinning and pruning on growth of loblolly pine (Pinus taeda L.) was established by Dr. James D. Burton in 1970 in a typical 12-year-old loblolly pine (plantation was 11 years old) stand planted by then the Georgia-Pacific Corporation in the southeastern corner of Arkansas. Basal area has been maintained at...

The Plantation Conversion Demonstration at the Crossett Experimental Forest--Implications For Converting Stands From Even-Aged to Uneven-Aged Structure

Treesearch

James M. Guldin; Robert M. Farrar

2002-01-01

In the absence of replicated studies, we used a case study demonstration to illustrate converting a 26-year-old even-aged loblolly pine (Pinus taeda L.) plantation to uneven-aged structure. Unreplicated treatments included maintaining even-aged structure through low thinning (thinning from below) to a residual basal area of 80 square feet per acre,...

Tumour cell heterogeneity maintained by cooperating subclones in Wnt-driven mammary cancers.

PubMed

Cleary, Allison S; Leonard, Travis L; Gestl, Shelley A; Gunther, Edward J

2014-04-03

Cancer genome sequencing studies indicate that a single breast cancer typically harbours multiple genetically distinct subclones. As carcinogenesis involves a breakdown in the cell-cell cooperation that normally maintains epithelial tissue architecture, individual subclones within a malignant microenvironment are commonly depicted as self-interested competitors. Alternatively, breast cancer subclones might interact cooperatively to gain a selective growth advantage in some cases. Although interclonal cooperation has been shown to drive tumorigenesis in fruitfly models, definitive evidence for functional cooperation between epithelial tumour cell subclones in mammals is lacking. Here we use mouse models of breast cancer to show that interclonal cooperation can be essential for tumour maintenance. Aberrant expression of the secreted signalling molecule Wnt1 generates mixed-lineage mammary tumours composed of basal and luminal tumour cell subtypes, which purportedly derive from a bipotent malignant progenitor cell residing atop a tumour cell hierarchy. Using somatic Hras mutations as clonal markers, we show that some Wnt tumours indeed conform to a hierarchical configuration, but that others unexpectedly harbour genetically distinct basal Hras mutant and luminal Hras wild-type subclones. Both subclones are required for efficient tumour propagation, which strictly depends on luminally produced Wnt1. When biclonal tumours were challenged with Wnt withdrawal to simulate targeted therapy, analysis of tumour regression and relapse revealed that basal subclones recruit heterologous Wnt-producing cells to restore tumour growth. Alternatively, in the absence of a substitute Wnt source, the original subclones often evolve to rescue Wnt pathway activation and drive relapse, either by restoring cooperation or by switching to a defector strategy. Uncovering similar modes of interclonal cooperation in human cancers may inform efforts aimed at eradicating tumour cell communities.

Differences in muscle fiber size and associated energetic costs in phylogenetically paired tropical and temperate birds.

PubMed

Jimenez, Ana Gabriela; Williams, Joseph B

2014-01-01

Tropical and temperate birds provide a unique system to examine mechanistic consequences of life-history trade-offs at opposing ends of the pace-of-life spectrum; tropical birds tend to have a slow pace of life whereas temperate birds the opposite. Birds in the tropics have a lower whole-animal basal metabolic rate and peak metabolic rate, lower rates of reproduction, and longer survival than birds in temperate regions. Although skeletal muscle has a relatively low tissue-specific metabolism at rest, it makes up the largest fraction of body mass and therefore contributes more to basal metabolism than any other tissue. A principal property of muscle cells that influences their rate of metabolism is fiber size. The optimal fiber size hypothesis attempts to link whole-animal basal metabolic rate to the cost of maintaining muscle mass by stating that larger fibers may be metabolically cheaper to maintain since the surface area∶volume ratio (SA∶V) is reduced compared with smaller fibers and thus the amount of area to transport ions is also reduced. Because tropical birds have a reduced whole-organism metabolism, we hypothesized that they would have larger muscle fibers than temperate birds, given that larger muscle fibers have reduced energy demand from membrane Na(+)-K(+) pumps. Alternatively, smaller muscle fibers could result in a lower capacity for shivering and exercise. To test this idea, we examined muscle fiber size and Na(+)-K(+)-ATPase activity in 16 phylogenetically paired species of tropical and temperate birds. We found that 3 of the 16 paired comparisons indicated that tropical birds had significantly larger fibers, contrary to our hypothesis. Our data show that SA∶V is proportional to Na(+)-K(+)-ATPase activity in muscles of birds.

Development of insulin resistance and endothelin-1 levels in the Zucker fatty rat.

PubMed

Berthiaume, Nathalie; Mika, Amanda K; Zinker, Bradley A

2003-07-01

In order to determine the effects of increasing insulin resistance on endothelin-1 (ET-1) levels, Zucker lean and fatty rats were studied at basal and during a complete nutrient meal tolerance test (MTT) at 7, 12, and 15 weeks of age. The fatty rats were mildly hyperglycemic, severely hyperinsulinemic and glucose-intolerant at all ages versus lean animals and this progressed with age within groups, as previously published. Basal ET-1 levels, at 7 weeks, were significantly increased in fatty versus lean rats (3.2+/-0.5 v 2.0+/-0.3 pg/mL, respectively; P<.05); however, we did not observe any significant basal difference at 12 or 15 weeks. At 7 weeks, ET-1 levels between fatty and lean rats were not different during the MTT (15 minutes: 2.9+/-0.4 v 2.7+/-0.7; 120 minutes: 6.5+/-0.8 v 6.6+/-0.5 pg/mL, fatty v lean, respectively). At 12 weeks, though there was no difference in basal levels, fatty rats had higher ET-1 levels during the MTT compared to lean animals (15 minutes: 6.9+/-1.4 v 1.8+/-0.4; 120 minutes: 9.4+/-1.7 v 3.2+/-0.5 pg/mL, respectively; P<.01). At 15 weeks, ET-1 levels during the MTT receded to levels similar to those observed at 7 weeks, which were significantly higher in fatty versus lean rats 15 minutes following the challenge (3.4+/-0.4 v 2.4+/-0.2 pg/mL, respectively; P<.05). In conclusion, ET-1 levels in the Zucker fatty rat: (1) were increased in the early stages of the progression of insulin resistance at 7 weeks, but were unchanged under basal conditions with age thereafter, and (2) were increased under nutrient challenge conditions with advanced insulin resistance up to 12 weeks, and were still significantly but to a lesser degree increased at 15 weeks of age. The explanation for these results and their relationship to the observed insulin resistance is unclear and will require further investigation.

EBSD analysis of subgrain boundaries and dislocation slip systems in Antarctic and Greenland ice

NASA Astrophysics Data System (ADS)

Weikusat, Ilka; Kuiper, Ernst-Jan N.; Pennock, Gill M.; Kipfstuhl, Sepp; Drury, Martyn R.

2017-09-01

Ice has a very high plastic anisotropy with easy dislocation glide on basal planes, while glide on non-basal planes is much harder. Basal glide involves dislocations with the Burgers vector b = 〈a〉, while glide on non-basal planes can involve dislocations with b = 〈a〉, b = [c], and b = 〈c + a〉. During the natural ductile flow of polar ice sheets, most of the deformation is expected to occur by basal slip accommodated by other processes, including non-basal slip and grain boundary processes. However, the importance of different accommodating processes is controversial. The recent application of micro-diffraction analysis methods to ice, such as X-ray Laue diffraction and electron backscattered diffraction (EBSD), has demonstrated that subgrain boundaries indicative of non-basal slip are present in naturally deformed ice, although so far the available data sets are limited. In this study we present an analysis of a large number of subgrain boundaries in ice core samples from one depth level from two deep ice cores from Antarctica (EPICA-DML deep ice core at 656 m of depth) and Greenland (NEEM deep ice core at 719 m of depth). EBSD provides information for the characterization of subgrain boundary types and on the dislocations that are likely to be present along the boundary. EBSD analyses, in combination with light microscopy measurements, are presented and interpreted in terms of the dislocation slip systems. The most common subgrain boundaries are indicative of basal 〈a〉 slip with an almost equal occurrence of subgrain boundaries indicative of prism [c] or 〈c + a〉 slip on prism and/or pyramidal planes. A few subgrain boundaries are indicative of prism 〈a〉 slip or slip of 〈a〉 screw dislocations on the basal plane. In addition to these classical polygonization processes that involve the recovery of dislocations into boundaries, alternative mechanisms are discussed for the formation of subgrain boundaries that are not related to the crystallography of the host grain.The finding that subgrain boundaries indicative of non-basal slip are as frequent as those indicating basal slip is surprising. Our evidence of frequent non-basal slip in naturally deformed polar ice core samples has important implications for discussions on ice about plasticity descriptions, rate-controlling processes which accommodate basal glide, and anisotropic ice flow descriptions of large ice masses with the wider perspective of sea level evolution.

Preliminary characterization of IL32 in basal-like/triple negative compared to other types of breast cell lines and tissues

PubMed Central

2014-01-01

Background Triple negative breast cancer (TNBC) and often basal-like cancers are defined as negative for estrogen receptor, progesterone receptor and Her2 gene expression. Over the past few years an incredible amount of data has been generated defining the molecular characteristics of both cancers. The aim of these studies is to better understand the cancers and identify genes and molecular pathways that might be useful as targeted therapies. In an attempt to contribute to the understanding of basal-like/TNBC, we examined the Gene Expression Omnibus (GEO) public datasets in search of genes that might define basal-like/TNBC. The Il32 gene was identified as a candidate. Findings Analysis of several GEO datasets showed differential expression of IL32 in patient samples previously designated as basal and/or TNBC compared to normal and luminal breast samples. As validation of the GEO results, RNA and protein expression levels were examined using MCF7 and MDA MB231 cell lines and tissue microarrays (TMAs). IL32 gene expression levels were higher in MDA MB231 compared to MCF7. Analysis of TMAs showed 42% of TNBC tissues and 25% of the non-TNBC were positive for IL32, while non-malignant patient samples and all but one hyperplastic tissue sample demonstrated lower levels of IL32 protein expression. Conclusion Data obtained from several publically available GEO datasets showed overexpression of IL32 gene in basal-like/TNBC samples compared to normal and luminal samples. In support of these data, analysis of TMA clinical samples demonstrated a particular pattern of IL32 differential expression. Considered together, these data suggest IL32 is a candidate suitable for further study. PMID:25100201

Dopamine and noradrenaline efflux in the prefrontal cortex in the light and dark period: effects of novelty and handling and comparison to the nucleus accumbens.

PubMed

Feenstra, M G; Botterblom, M H; Mastenbroek, S

2000-01-01

We used on-line microdialysis measurements of dopamine and noradrenaline extracellular concentrations in the medial prefrontal cortex of awake, freely moving rats during the dark and the light period of the day to study whether (i) basal efflux would be higher in the active, dark period than in the inactive, light period; (ii) the activation induced by environmental stimuli would be dependent on these conditions. When determined one day after cannula placement, noradrenaline and dopamine levels were higher during the dark. Maximal relative increases induced by novelty and handling were 150% and 175-200%, respectively, and were very similar in the light and the dark, but the net increases were higher in the dark. Separate groups were tested one week after cannula placement to ensure recovery of possibly disturbed circadian rhythms. While basal levels in the dark were now approximately twice those in the light, the maximal relative and net increases after both novelty and handling were very similar. Basal levels of dopamine in the nucleus accumbens (one day after cannula placement) were not different in the light or dark, but were increased by novelty and handling to about 130% only in the light period, not in the dark. Thus, in the prefrontal cortex, dopamine strongly resembles noradrenaline, in that basal efflux was state dependent, whereas activation by stimuli was not. In the nucleus accumbens, basal dopamine efflux was not state dependent, but activation by stimuli was. These results suggest that there are differential effects of circadian phase on basal activity and responsiveness of the mesolimbic vs the mesocortical dopamine system.

Carbohydrate-to-insulin ratio is estimated from 300-400 divided by total daily insulin dose in type 1 diabetes patients who use the insulin pump.

PubMed

Kuroda, Akio; Yasuda, Tetsuyuki; Takahara, Mitsuyoshi; Sakamoto, Fumie; Kasami, Ryuichi; Miyashita, Kazuyuki; Yoshida, Sumiko; Kondo, Eri; Aihara, Ken-ichi; Endo, Itsuro; Matsuoka, Taka-aki; Kaneto, Hideaki; Matsumoto, Toshio; Shimomura, Iichiro; Matsuhisa, Munehide

2012-11-01

To optimize insulin dose using insulin pump, basal and bolus insulin doses are widely calculated from total daily insulin dose (TDD). It is recommended that total daily basal insulin dose (TBD) is 50% of TDD and that the carbohydrate-to-insulin ratio (CIR) equals 500 divided by TDD. We recently reported that basal insulin requirement is approximately 30% of TDD. We therefore investigated CIR after adjustment of the proper basal insulin rate. Forty-five Japanese patients with type 1 diabetes were investigated during several weeks of hospitalization. The patients were served standard diabetes meals (25-30 kcal/kg of ideal body weight). Each meal omission was done to confirm basal insulin rate. Target blood glucose level was set at 100 and 150 mg/dL before and 2 h after each meal, respectively. After the basal insulin rate was fixed and target blood glucose levels were achieved, TBD, CIR, TDD, and their products were determined. Mean (±SD) blood glucose levels before and 2 h after meals were 121±47 and 150±61 mg/dL, respectively. TDD was 31.5±9.0 U, and TBD was 27.0±6.5% of TDD. CIR×TDD of breakfast was significantly lower than those of lunch and supper (288±73 vs. 408±92 and 387±83, respectively; P<0.01). CIR has diurnal variance and is estimated from the formula CIR=300/TDD at breakfast or CIR=400/TDD at lunch and supper in type 1 diabetes patients. These results indicate that the insulin dose has been underestimated by using previously established calculations.

RhoA/ROCK pathway is the major molecular determinant of basal tone in intact human internal anal sphincter.

PubMed

Rattan, Satish; Singh, Jagmohan

2012-04-01

The knowledge of molecular control mechanisms underlying the basal tone in the intact human internal anal sphincter (IAS) is critical for the pathophysiology and rational therapy for a number of debilitating rectoanal motility disorders. We determined the role of RhoA/ROCK and PKC pathways by comparing the effects of ROCK- and PKC-selective inhibitors Y 27632 and Gö 6850 (10(-8) to 10(-4) M), respectively, on the basal tone in the IAS vs. the rectal smooth muscle (RSM). Western blot studies were performed to determine the levels of RhoA/ROCK II, PKC-α, MYPT1, CPI-17, and MLC(20) in the unphosphorylated and phosphorylated forms, in the IAS vs. RSM. Confocal microscopic studies validated the membrane distribution of ROCK II. Finally, to confirm a direct relationship, we examined the enzymatic activities and changes in the basal IAS tone and p-MYPT1, p-CPI-17, and p-MLC(20), before and after Y 27632 and Gö 6850. Data show higher levels of RhoA/ROCK II and related downstream signal transduction proteins in the IAS vs. RSM. In addition, data show a significant correlation between the active RhoA/ROCK levels, ROCK enzymatic activity, downstream proteins, and basal IAS tone, before and after ROCK inhibitor. From these data we conclude 1) RhoA/ROCK and downstream signaling are constitutively active in the IAS, and this pathway (in contrast with PKC) is the critical determinant of the basal tone in intact human IAS; and 2) RhoA and ROCK are potential therapeutic targets for a number of rectoanal motility disorders for which currently there is no satisfactory treatment.

RhoA/ROCK pathway is the major molecular determinant of basal tone in intact human internal anal sphincter

PubMed Central

Singh, Jagmohan

2012-01-01

The knowledge of molecular control mechanisms underlying the basal tone in the intact human internal anal sphincter (IAS) is critical for the pathophysiology and rational therapy for a number of debilitating rectoanal motility disorders. We determined the role of RhoA/ROCK and PKC pathways by comparing the effects of ROCK- and PKC-selective inhibitors Y 27632 and Gö 6850 (10−8 to 10−4 M), respectively, on the basal tone in the IAS vs. the rectal smooth muscle (RSM). Western blot studies were performed to determine the levels of RhoA/ROCK II, PKC-α, MYPT1, CPI-17, and MLC20 in the unphosphorylated and phosphorylated forms, in the IAS vs. RSM. Confocal microscopic studies validated the membrane distribution of ROCK II. Finally, to confirm a direct relationship, we examined the enzymatic activities and changes in the basal IAS tone and p-MYPT1, p-CPI-17, and p-MLC20, before and after Y 27632 and Gö 6850. Data show higher levels of RhoA/ROCK II and related downstream signal transduction proteins in the IAS vs. RSM. In addition, data show a significant correlation between the active RhoA/ROCK levels, ROCK enzymatic activity, downstream proteins, and basal IAS tone, before and after ROCK inhibitor. From these data we conclude 1) RhoA/ROCK and downstream signaling are constitutively active in the IAS, and this pathway (in contrast with PKC) is the critical determinant of the basal tone in intact human IAS; and 2) RhoA and ROCK are potential therapeutic targets for a number of rectoanal motility disorders for which currently there is no satisfactory treatment. PMID:22241857

Increased Hepatic Glucose Production in Fetal Sheep With Intrauterine Growth Restriction Is Not Suppressed by Insulin

PubMed Central

Thorn, Stephanie R.; Brown, Laura D.; Rozance, Paul J.; Hay, William W.; Friedman, Jacob E.

2013-01-01

Intrauterine growth restriction (IUGR) increases the risk for metabolic disease and diabetes, although the developmental origins of this remain unclear. We measured glucose metabolism during basal and insulin clamp periods in a fetal sheep model of placental insufficiency and IUGR. Compared with control fetuses (CON), fetuses with IUGR had increased basal glucose production rates and hepatic PEPCK and glucose-6-phosphatase expression, which were not suppressed by insulin. In contrast, insulin significantly increased peripheral glucose utilization rates in CON and IUGR fetuses. Insulin robustly activated AKT, GSK3β, and forkhead box class O (FOXO)1 in CON and IUGR fetal livers. IUGR livers, however, had increased basal FOXO1 phosphorylation, nuclear FOXO1 expression, and Jun NH2-terminal kinase activation during hyperinsulinemia. Expression of peroxisome proliferator–activated receptor γ coactivator 1α and hepatocyte nuclear factor-4α were increased in IUGR livers during basal and insulin periods. Cortisol and norepinephrine concentrations were positively correlated with glucose production rates. Isolated IUGR hepatocytes maintained increased glucose production in culture. In summary, fetal sheep with IUGR have increased hepatic glucose production, which is not suppressed by insulin despite insulin sensitivity for peripheral glucose utilization. These data are consistent with a novel mechanism involving persistent transcriptional activation in the liver that seems to be unique in the fetus with IUGR. PMID:22933111

Fasting glucose and postprandial glycemia: which is the best target for improving outcomes? The Apollo and 4-T Trials.

PubMed

Monnier, Louis; Colette, Claude

2008-11-01

Two studies, the Apollo and 4-T Trials, were conducted in order to determine which insulin regimen (basal or prandial) is the most efficient for the treatment of insulin-requiring type 2 diabetic patients. Both trials compared treatments using prandial insulins (aspart or lispro) three times daily with more classical insulin strategies using basal insulin given once daily (glargine or detemir) or twice daily if required (detemir in the 4-T Study). Both studies showed that a therapeutic regimen involving prandial insulin resulted in equal (Apollo Study) or greater (4-T Study) reductions in patients' HbA(1c) levels than basal insulin regimens. However, the prandial insulin strategies were accompanied by higher risks of hypoglycemia and greater weight gain. As a consequence, the investigators of the two studies concluded that basal insulin once daily provides a simple and effective option with less adverse effects than prandial insulin three times a day. Such conclusions are certainly important for guiding strategies in the vast majority of type 2 diabetic patients who require an add-on insulin therapy. However, the authors' opinion is that the choice between either basal or prandial insulin alone and combined insulin regimens with basal and prandial insulin should be tailored according to the patient's clinical status by paying more attention to the respective contributions of basal and prandial hyperglycemia to their overall hyperglycemia. This recommendation seems to be particularly important when insulin treatment is initiated in patients exhibiting HbA(1c) levels between 7.0 and 8.0%.

Nicergoline increases serum substance P levels in patients with an ischaemic stroke.

PubMed

Nishiyama, Yasuhiro; Abe, Arata; Ueda, Masayuki; Katsura, Ken-ichiro; Katayama, Yasuo

2010-01-01

Aspiration pneumonia is one of the most important complications following ischaemic stroke, and a leading cause of mortality in stroke patients. This is particularly prevalent in patients with involvement of the basal ganglia, which may be due to impaired neurotransmission through lack of production of substance P. Consecutive patients in the chronic stage, 1-3 months after cerebral ischaemic infarction, were assessed for basal ganglia involvement by magnetic resonance imaging. The patients were randomised to 4 weeks of treatment with (n = 25) or without (n = 25) nicergoline (15 mg t.i.d.). Serum concentration of substance P was measured by radioimmunoassay. At entry to the study, mean concentration of substance P was significantly (p < 0.001) lower in patients with bilateral basal ganglia lesions than in patients with no or unilateral basal ganglia involvement. Nicergoline administration caused a significant (p = 0.021) increase from baseline in mean substance P concentration. No significant change was seen in the nicergoline-untreated patients (p = 0.626). Among the patients who received nicergoline, 11 patients had bilateral basal ganglia involvement and there was no significant mean change in substance P in these patients, whereas there was a significant increase (p = 0.032) in the 14 nicergoline-treated patients with no or unilateral basal ganglia involvement. The present study suggests a possible effect of nicergoline to increase substance P level in ischaemic stroke patients with partial damage to basal ganglia, who have a decreased swallowing response and consequent risk of aspiration pneumonia. Further trials of nicergoline treatment in patients at risk for aspiration pneumonia are warranted. (c) 2009 S. Karger AG, Basel.

Potential long-term effects of MDMA on the basal ganglia-thalamocortical circuit: a proton MR spectroscopy and diffusion-tensor imaging study.

PubMed

Liu, Hua-Shan; Chou, Ming-Chung; Chung, Hsiao-Wen; Cho, Nai-Yu; Chiang, Shih-Wei; Wang, Chao-Ying; Kao, Hung-Wen; Huang, Guo-Shu; Chen, Cheng-Yu

2011-08-01

To investigate the effects of 3,4-methylenedioxymethamphetamine (MDMA, commonly known as "ecstasy") on the alterations of brain metabolites and anatomic tissue integrity related to the function of the basal ganglia-thalamocortical circuit by using proton magnetic resonance (MR) spectroscopy and diffusion-tensor MR imaging. This study was approved by a local institutional review board, and written informed consent was obtained from all subjects. Thirty-one long-term (>1 year) MDMA users and 33 healthy subjects were enrolled. Proton MR spectroscopy from the middle frontal cortex and bilateral basal ganglia and whole-brain diffusion-tensor MR imaging were performed with a 3.0-T system. Absolute concentrations of metabolites were computed, and diffusion-tensor data were registered to the International Consortium for Brain Mapping template to facilitate voxel-based group comparison. The mean myo-inositol level in the basal ganglia of MDMA users (left: 4.55 mmol/L ± 2.01 [standard deviation], right: 4.48 mmol/L ± 1.33) was significantly higher than that in control subjects (left: 3.25 mmol/L ± 1.30, right: 3.31 mmol/L ± 1.19) (P < .001). Cumulative lifetime MDMA dose showed a positive correlation with the levels of choline-containing compounds (Cho) in the right basal ganglia (r = 0.47, P = .02). MDMA users also showed a significant increase in fractional anisotropy (FA) in the bilateral thalami and significant changes in water diffusion in several regions related to the basal ganglia-thalamocortical circuit as compared with control subjects (P < .05; cluster size, >50 voxels). Increased myo-inositol and Cho concentrations in the basal ganglia of MDMA users are suggestive of glial response to degenerating serotonergic functions. The abnormal metabolic changes in the basal ganglia may consequently affect the inhibitory effect of the basal ganglia to the thalamus, as suggested by the increased FA in the thalamus and abnormal changes in water diffusion in the corresponding basal ganglia-thalamocortical circuit. © RSNA, 2011.

Parkinson’s disease as a system-level disorder

PubMed Central

Caligiore, Daniele; Helmich, Rick C; Hallett, Mark; Moustafa, Ahmed A; Timmermann, Lars; Toni, Ivan; Baldassarre, Gianluca

2016-01-01

Traditionally, the basal ganglia have been considered the main brain region implicated in Parkinson’s disease. This single area perspective gives a restricted clinical picture and limits therapeutic approaches because it ignores the influence of altered interactions between the basal ganglia and other cerebral components on Parkinsonian symptoms. In particular, the basal ganglia work closely in concert with cortex and cerebellum to support motor and cognitive functions. This article proposes a theoretical framework for understanding Parkinson’s disease as caused by the dysfunction of the entire basal ganglia–cortex–cerebellum system rather than by the basal ganglia in isolation. In particular, building on recent evidence, we propose that the three key symptoms of tremor, freezing, and impairments in action sequencing may be explained by considering partially overlapping neural circuits including basal ganglia, cortical and cerebellar areas. Studying the involvement of this system in Parkinson’s disease is a crucial step for devising innovative therapeutic approaches targeting it rather than only the basal ganglia. Possible future therapies based on this different view of the disease are discussed. PMID:28725705

Delayed peak response of cortisol to insulin tolerance test in patients with Prader-Willi syndrome.

PubMed

Oto, Yuji; Matsubara, Keiko; Ayabe, Tadayuki; Shiraishi, Masahisa; Murakami, Nobuyuki; Ihara, Hiroshi; Matsubara, Tomoyo; Nagai, Toshiro

2018-06-01

Deaths among children with Prader-Willi syndrome (PWS) are often related to only mild or moderate upper respiratory tract infections, and many causes of death remain unexplained. Several reports have hypothesized that patients with PWS may experience latent central adrenal insufficiency. However, whether PWS subjects suffer from alteration of the hypothalamus-pituitary-adrenal (HPA) axis remains unclear. This study aimed to explore the HPA axis on PWS. We evaluated the HPA axis in 36 PWS patients (24 males, 12 females; age range, 7 months to 12 years; median age 2.0 years; interquartile range [IQR], 1.5-3.4 years) using an insulin tolerance test (ITT) in the morning between 08:00 and 11:00. For comparison, ITT results in 37 age-matched healthy children evaluated for short stature were used as controls. In PWS patients, basal levels of adrenocorticotropic hormone (ACTH) were 13.5 pg/ml (IQR, 8.3-27.5 pg/ml) and basal levels of cortisol were 18.0 μg/dl (IQR, 14.2-23.7 μg/dl). For all patients, cortisol levels at 60 min after stimulation were within the reference range (>18.1 μg/dl), with a median peak of 41.5 μg/dl (IQR, 32.3-48.6 μg/dl). Among control children, basal level of ACTH and basal and peak levels of cortisol were 10.9 (IQR, 8.5-22.0 pg/ml), 15.6 (IQR, 11.9-21.6 μg/dl), and 27.8 μg/dl (IQR, 23.7-30.5 μg/dl), respectively. Basal and peak levels of cortisol were all within normal ranges, but peak response of cortisol to ITT was delayed in the majority of PWS patients (64%). Although the mechanism remains unclear, this delay may signify the existence of central obstacle in adjustment of the HPA axis. © 2018 Wiley Periodicals, Inc.

Investigating the microstructural and neurochemical environment within the basal ganglia of current methamphetamine abusers.

PubMed

Lin, Joanne C; Jan, Reem K; Kydd, Rob R; Russell, Bruce R

2015-04-01

Methamphetamine is a highly addictive psychostimulant and the medical, social, and economic consequences associated with its use have become a major international problem. Current evidence has shown methamphetamine to be particularly neurotoxic to dopamine neurons and striatal structures within the basal ganglia. A previous study from our laboratory demonstrated larger putamen volumes in actively using methamphetamine-dependent participants. The purpose of this current study was to determine whether striatal structures in the same sample of participants also exhibit pathology on the microstructural and molecular level. Diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) were carried out in current methamphetamine users (n = 18) and healthy controls (n = 22) to investigate diffusion indices and neurometabolite levels in the basal ganglia. Contrary to findings from previous DTI and MRS studies, no significant differences in diffusion indices or metabolite levels were observed in the basal ganglia regions of current methamphetamine users. These findings differ from those reported in abstinent users and the absence of diffusion and neurochemical abnormalities may suggest that striatal enlargement in current methamphetamine use may be due to mechanisms other than edema and glial proliferation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Basal Cell Carcinoma Arising in a Breast Augmentation Scar.

PubMed

Edwards, Lisa R; Cresce, Nicole D; Russell, Mark A

2017-04-01

We report a case of a 46-year-old female who presented with a persistent lesion on the inferior right breast. The lesion was located within the scar from a breast augmentation procedure 12 years ago. The lesion had been treated as several conditions with no improvement. Biopsy revealed a superficial and nodular basal cell carcinoma, and the lesion was successfully removed with Mohs micrographic surgery. Basal cell carcinoma arising in a surgical scar is exceedingly rare with only 13 reported cases to date. This is the first reported case of basal cell carcinoma arising in a breast augmentation scar. We emphasize the importance of biopsy for suspicious lesions or those refractory to treatment, particularly those lesions that form within a scar. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Transient hypogonadotropic hypogonadism in an amateur kickboxer after head trauma.

PubMed

Tanriverdi, F; Unluhizarci, K; Selcuklu, A; Casanueva, F F; Kelestimur, F

2007-02-01

Traumatic brain injury (TBI) is a frequent health problem and increased prevalence of neurendocrine dysfunction in patients with TBI has been reported. Sports injuries and particularly boxing may result in pituitary dysfunction. However, transient hypogonadotropic hypogonadism after an acute head trauma due to boxing and/or kickboxing has not been defined yet. We describe the case of a 20-yr-old male amateur kickboxer who was admitted to hospital complaining of decreased libido and impotence 2 weeks after an intensive bout. Basal hormone levels were compatible with mild hyperprolactinemia and hypogonadotpopic hypogonadism. GH axis was evaluated by GHRH+GHRP-6 test and peak GH level was within normal reference range. Three months later his complaints improved and abnormalities in basal hormone levels normalized. He was also re-evaluated 9 months after the first evaluation; basal hormone levels were within normal ranges and he had no complaints. In conclusion acute head trauma due to kickboxing may cause transient gonadotropin deficiency. Therefore, screening the pituitary functions of sportsmen dealing with combative sports is crucial.

Hypothalamic stimulation and baroceptor reflex interaction on renal nerve activity.

NASA Technical Reports Server (NTRS)

Wilson, M. F.; Ninomiya, I.; Franz, G. N.; Judy, W. V.

1971-01-01

The basal level of mean renal nerve activity (MRNA-0) measured in anesthetized cats was found to be modified by the additive interaction of hypothalamic and baroceptor reflex influences. Data were collected with the four major baroceptor nerves either intact or cut, and with mean aortic pressure (MAP) either clamped with a reservoir or raised with l-epinephrine. With intact baroceptor nerves, MRNA stayed essentially constant at level MRNA-0 for MAP below an initial pressure P1, and fell approximately linearly to zero as MAP was raised to P2. Cutting the baroceptor nerves kept MRNA at MRNA-0 (assumed to represent basal central neural output) independent of MAP. The addition of hypothalamic stimulation produced nearly constant increments in MRNA for all pressure levels up to P2, with complete inhibition at some level above P2. The increments in MRNA depended on frequency and location of the stimulus. A piecewise linear model describes MRNA as a linear combination of hypothalamic, basal central neural, and baroceptor reflex activity.

Melatonin in octopus (Octopus vulgaris): tissue distribution, daily changes and relation with serotonin and its acid metabolite.

PubMed

Muñoz, José L P; López Patiño, Marcos A; Hermosilla, Consuelo; Conde-Sieira, Marta; Soengas, José L; Rocha, Francisco; Míguez, Jesús M

2011-08-01

Information regarding melatonin production in molluscs is very limited. In this study the presence and daily fluctuations of melatonin levels were investigated in hemolymph, retina and nervous system-related structures in the cephalopod Octopus vulgaris. Adult animals were maintained in captivity under natural photoperiod and killed at different times in a regular daily cycle. Levels of melatonin, serotonin (5-HT) and its acid metabolite (5-hydroxyindole acetic acid, 5-HIAA) in the hemolymph, retina, optic lobe, and cerebral ganglion were assayed by HPLC. Melatonin content fluctuated rhythmically in the retina and hemolymph, peaking at night. In the retina, but not in the other neural tissues, the rhythm was opposite to that of 5-HT, which displayed basal levels at night. Also, 5-HIAA levels in the retina were higher during the night, supporting that rhythmic melatonin production could be linked to diurnal changes in 5-HT degradation. The high levels of melatonin found in the retina point to it as the major source of melatonin in octopus; in addition, a large variation of melatonin content was found in the optic lobe with maximal values at night. All these data suggest that melatonin might play a role in the transduction of the light-dark cycle information for adjustment of rhythmic physiological events in cephalopods.

Heat shock protein-27 protects human bronchial epithelial cells against oxidative stress–mediated apoptosis: possible implication in asthma

PubMed Central

Merendino, Anna M.; Paul, Catherine; Vignola, Antonio M.; Costa, Maria A.; Melis, Mario; Chiappara, Giuseppina; Izzo, V.; Bousquet, J.; Arrigo, André-Patrick

2002-01-01

Inflammation of the human bronchial epithelium, as observed in asthmatics, is characterized by the selective death of the columnar epithelial cells, which desquamate from the basal cells. Tissue repair initiates from basal cells that resist inflammation. Here, we have evaluated the extent of apoptosis as well as the Hsp27 level of expression in epithelial cells from bronchial biopsy samples taken from normal and asthmatic subjects. Hsp27 is a chaperone whose expression protects against oxidative stress. We report that in asthmatic subjects the basal epithelium cells express a high level of Hsp27 but no apoptotic morphology. In contrast, apoptotic columnar cells are devoid of Hsp27 expression. Moreover, we observed a decreased resistance to hydrogen peroxide–induced apoptosis in human bronchial epithelial 16–HBE cells when they were genetically modified to express reduced levels of Hsp27. PMID:12482203

The Oncogenic Role of RhoGAPs in Basal-Like Breast Cancer

DTIC Science & Technology

2015-02-01

cell lines, and mouse models . c) In vivo tumorigenesis and metastasis assays. Milestones: Identify whether ArhGAP11A and RacGAP1 can promote tumor growth...also upregulated in basal (C3(I)-Tag) but not luminal (MMTV-Neu) genetically- engineered mouse models (Fig. 1B). At the protein level, RacGAP1 was...hypothesis that these RhoGAPs are indeed playing an oncogenic role in these cells. Human Tumors Mouse Model Tumors Normal Luminal A Basal-like Normal

Diversity of olfactomedin proteins in the sea urchin.

PubMed

Hillier, Brian J; Moy, Gary W; Vacquier, Victor D

2007-06-01

Olfactomedin (OLF) domain proteins maintain extracellular protein-protein interactions in diverse phyla. Only one OLF family member, amassin-1, has been described from the sea urchin Strongylocentrotus purpuratus, a basal invertebrate deuterostome. Amassin-1 mediates intercellular adhesion of coelomocytes (immunocytes). Here we describe the protein structural features of four additional OLF proteins, the total for the genome being five. Phylogenetically, four of these proteins (the amassins) form a subgroup among previously identified OLF proteins. The fifth OLF protein is within the colmedin subfamily and contains a type II transmembrane domain, collagen repeats, and an OLF domain. Sea urchin OLF proteins represent an intermediate diversification between protostomes and vertebrates. Transcripts of all five OLF family members are in coelomocytes and adult radial nerve tissue. Transcripts for some OLF proteins increase during late larval stages. Transcript levels for amassin-1 increase 1,000,000-fold, coinciding with formation of the adult urchin rudiment within the larval body.

Endocrine Function In Naturally Long-Living Small Mammals

PubMed Central

Buffenstein, Rochelle; Pinto, Mario

2015-01-01

The complex, highly integrative endocrine system regulates all aspects of somatic maintenance and reproduction and has been widely implicated as an important determinant of longevity in short-lived traditional model organisms of aging research. Genetic or experimental manipulation of hormone profiles in mice has been proven to definitively alter longevity. These hormonally induced lifespan extension mechanisms may not necessarily be relevant to humans and other long-lived organisms that naturally show successful slow aging. Long-lived species may have evolved novel anti-aging defenses germane to naturally retarding the aging process. Here we examine the available endocrine data associated with the vitamin D, insulin, grlucocorticoid and thyroid endocrine systems of naturally long-living small mammals. Generally, long-living rodents and bats maintain tightly regulated lower basal levels of these key pleiotropic hormones than shorter-lived rodents. Similarities with genetically manipulated suggest that evolutionarily wellconserved hormonal mechanisms are integrally involved in lifespan determination. PMID:18674586

Creating single-copy genetic circuits

PubMed Central

Lee, Jeong Wook; Gyorgy, Andras; Cameron, D. Ewen; Pyenson, Nora; Choi, Kyeong Rok; Way, Jeffrey C.; Silver, Pamela A.; Del Vecchio, Domitilla; Collins, James J.

2017-01-01

SUMMARY Synthetic biology is increasingly used to develop sophisticated living devices for basic and applied research. Many of these genetic devices are engineered using multi-copy plasmids, but as the field progresses from proof-of-principle demonstrations to practical applications, it is important to develop single-copy synthetic modules that minimize consumption of cellular resources and can be stably maintained as genomic integrants. Here we use empirical design, mathematical modeling and iterative construction and testing to build single-copy, bistable toggle switches with improved performance and reduced metabolic load that can be stably integrated into the host genome. Deterministic and stochastic models led us to focus on basal transcription to optimize circuit performance and helped to explain the resulting circuit robustness across a large range of component expression levels. The design parameters developed here provide important guidance for future efforts to convert functional multi-copy gene circuits into optimized single-copy circuits for practical, real-world use. PMID:27425413

House dust mite-specific immunotherapy alters the basal expression of T regulatory and FcεRI pathway genes.

PubMed

Pevec, Branko; Radulovic Pevec, Mira; Stipic Markovic, Asja; Batista, Irena; Rijavec, Matija; Silar, Mira; Kosnik, Mitja; Korosec, Peter

2012-01-01

Regulatory T (Treg) cells and IgE-mediated signaling pathways could play important roles in the induction of allergen tolerance during house dust mite-specific subcutaneous immunotherapy (HDM-SCIT). Our aim was to compare the basal expression levels of Treg, T helper 1 (Th1) and Th2 transcription factors and components involved in IgE-mediated signaling in healthy subjects with those in HDM-allergic patients both untreated and successfully treated with HDM-SCIT. Thirty-nine HDM-allergic patients who completed a 3- to 5-year course of mite extract SCIT, 20 mite-allergic controls and 25 healthy controls participated in this study. The efficacy of SCIT was monitored using skin-prick tests (SPTs), total immunoglobulin E (tIgE), specific IgE (sIgE), sIgG(4), nasal challenge and visual analog scale (VAS) scores at several time points. The mRNA levels of forkhead box protein 3 (FOXP3), T-BET, GATA-3, FcεRI, spleen tyrosine kinase (Syk), phosphatidylinositol 3 kinase (PI3K) and SH2 domain-containing inositol phosphatase (SHIP) were quantified by real-time RT-PCR using nonstimulated whole blood samples. Decreased wheal sizes and VAS scores, negative challenges and increased sIgG(4) levels indicated that SCIT was effective in the treated patients. Basal expression levels of FOXP3 and GATA-3 decreased and T-BET levels increased in both treated patients and in healthy controls compared to untreated patients. The IgE-mediated pathway kinases Syk and PI3K exhibited reduced expression, whereas SHIP phosphatase levels were elevated in both treated patients and healthy controls relative to untreated patients. The expression levels of FcεRI were not significantly altered. Immunotherapy using HDM extracts results in a modification of the basal expression levels of several IgE-related signaling factors and induces a highly significant upregulation of Th1-response and downregulation of Th2-response transcription factors. Interestingly, this therapy also appears to reduce the basal expression of FOXP3. Copyright © 2012 S. Karger AG, Basel.

Distinct expression patterns of glycoprotein hormone-alpha2 and -beta5 in a basal chordate suggest independent developmental functions.

PubMed

Dos Santos, Sandra; Bardet, Claire; Bertrand, Stephanie; Escriva, Hector; Habert, Damien; Querat, Bruno

2009-08-01

The vertebrate glycoprotein hormones (GpHs), gonadotropins and thyrotropin, are heterodimers composed of a common alpha- and specific beta-subunit. The recombinant heterodimer of two additional, structurally related proteins identified in vertebrate and protostome genomes, the glycoproteins-alpha2 (GPA2) and-beta5 (GPB5), was shown to activate the thyrotropin receptor and was therefore named thyrostimulin. However, differences in tissue distribution and expression levels of these proteins suggested that they might act as nonassociated factors, prompting further investigation on these proteins. In this study we show that GPA2 and GPB5 appeared with the emergence of bilateria and were maintained in most groups. These genes are tightly associated at the genomic level, an association, however, lost in tetrapods. Our structural and genomic environment comparison reinforces the hypothesis of their phylogenetic relationships with GpH-alpha and -beta. In contrast, the glycosylation status of GPA2 and GPB5 is highly variable further questioning heterodimer secretory efficiency and activity. As a first step toward understanding their function, we investigated the spatiotemporal expression of GPA2 and GPB5 genes at different developmental stages in a basal chordate, the amphioxus. Expression of GPB5 was essentially ubiquitous with an anteroposterior gradient in embryos. GPA2 embryonic and larvae expression was restricted to specific areas and, interestingly, partially overlapped that of a GpH receptor-related gene. In conclusion, we speculate that GPA2 and GPB5 have nondispensable and coordinated functions related to a novelty appeared with bilateria. These proteins would be active during embryonic development in a manner that does not require their heterodimerization.

Disruption of thyroid hormone sulfotransferase activity by brominated flame retardant chemicals in the human choriocarcinoma placenta cell line, BeWo.

PubMed

Leonetti, Christopher P; Butt, Craig M; Stapleton, Heather M

2018-04-01

Brominated flame retardants (BFRs) have been shown to disrupt thyroid hormone (TH) homeostasis through multiple mechanisms, including inhibition of enzymes that regulate intracellular levels of THs, such as sulfotransferases (SULTs). The placenta plays a critical role in helping to maintain TH levels during fetal development and expresses SULTs. This is concerning given that disruption of TH regulation within the placenta could potentially harm the developing fetus. In this study, we investigated the effects of two polybrominated diphenyl ethers (PBDEs), two hydroxylated PBDEs, and 2,4,6-tribromophenol (2,4,6-TBP) on TH SULT activity in a choriocarcinoma placenta cell line (BeWo). BeWo cells were exposed to BFR concentrations up to 1 μM for 1-24 h to investigate changes in basal SULT activity and in mRNA expression of several TH regulating genes. 2,4,6-TBP was the most potent inhibitor of basal 3,3'-T2 SULT activity at all exposure durations, decreasing activity by as much as 86% after 24 h of exposure. BDE-99, 3-OH BDE-47, and 6-OH BDE-47 also decreased 3,3'-T2 SULT activity by 23-42% at concentrations of 0.5 μM and 1.0 μM following 24 h exposures. BDE-47 had no effect on SULT activity, and there was no observed effect of any BFR exposure on expression of SULT1A1, or thyroid nuclear receptors alpha or beta. This research demonstrates that total TH SULT activity in placental cells are sensitive to BFR exposure; however, the mechanisms and consequences have yet to be fully elucidated. Copyright © 2017 Elsevier Ltd. All rights reserved.

Serologic control against hepatitis B virus among dental students of the University of Granada, Spain.

PubMed

Arias-Moliz, M-T; Rojas, L; Liébana-Cabanillas, F; Bernal, C; Castillo, F; Rodríguez-Archilla, A; Castillo, A; Liébana, J

2015-09-01

To evaluate the immunological situation against hepatitis B virus (HBV) of a cohort of dentistry students, to analyze the behavior of the levels of hepatitis B surface antigen (anti-HBs) after the administration of one or three vaccine doses, and to determine the influence of age and sex on the immune response. This retrospective cohort study included students attending the School of Dentistry of the institution where the study was performed from 2005 to 2012 who had completed the public health vaccination calendar for HBV at the age of 12-13. Data on age, sex, basal anti-HBs levels, post-vaccination anti-HBs results and final anti-HBs levels were collected. Comparisons of the basal and final levels, as well as associations regarding age and sex, were performed by means of the Student t and Chi-square tests. Of the 359 students, 97 (27.02%) had basal antibody concentrations <10 mIU/ml, whereas in 262 the levels of anti-HBs were ≥10 mIU/ml (72.98%). Of the 288 participating students who completed the School's protocol for immunization, 287 (99.65%) attained a level of protection ≥10 mIU/ml. Globally, there were statistically significant differences between the basal antibody levels and those achieved after administration of the vaccine and booster, but no association with age or sex was observed. About 70% of dental students vaccinated as pre-adolescents had serologic evidence of protection against HBV. Administering a booster is associated with the presence of an excellent immune memory. There is clearly a need to reinforce control of the antibody levels in groups at risk, such as Dentistry students.

Polyunsaturated fatty acids reduce insulin and very low density lipoprotein levels in broiler chickens.

PubMed

Crespo, N; Esteve-Garcia, E

2003-07-01

An experiment was conducted to study the effect of different dietary fatty acid profiles on plasma levels of insulin, very low density lipoproteins (VLDL), cholesterol, and glucose. Diets with four types of fat (tallow, olive, sunflower, and linseed oils) at an inclusion level of 10% and a basal diet without additional fat were administered to female broiler chickens. Serum insulin, cholesterol, and plasma VLDL were affected by the different treatments; however, glucose concentrations were similar among treatments. In the fasted state, broilers fed diets with sunflower or linseed oil presented lower levels of insulin and cholesterol with respect to those fed tallow or olive oil (P < 0.05). VLDL in the fasted state was reduced in broilers fed sunflower and linseed oils (P < 0.05) with respect to those fed tallow, olive oil, or the basal diet. Plasma levels of VLDL were only significantly correlated with abdominal fat in birds fed the basal diet, in the fed and in the fasted state, and in those fed linseed oil in the fed state (P < 0.05). Results of this experiment suggest that higher insulin levels in broilers fed diets rich in saturated fatty acids could be related to higher fat deposition. Fat deposition in birds fed high fat diets was not correlated with circulating VLDL, which suggested direct dietary fat deposition, except for birds fed linseed oil diets. Although birds fed linseed oil diets presented lower levels of VLDL than those fed tallow, olive oil, or the basal diet, the higher correlation with abdominal fat suggests that in these birds, fat deposition is more dependent on hepatic VLDL secretion, despite the high dietary fat level.

Metabolic biomarkers for response to PI3K inhibition in basal-like breast cancer

PubMed Central

2013-01-01

Introduction The phosphatidylinositol 3-kinase (PI3K) pathway is frequently activated in cancer cells through numerous mutations and epigenetic changes. The recent development of inhibitors targeting different components of the PI3K pathway may represent a valuable treatment alternative. However, predicting efficacy of these drugs is challenging, and methods for therapy monitoring are needed. Basal-like breast cancer (BLBC) is an aggressive breast cancer subtype, frequently associated with PI3K pathway activation. The objectives of this study were to quantify the PI3K pathway activity in tissue sections from xenografts representing basal-like and luminal-like breast cancer before and immediately after treatment with PI3K inhibitors, and to identify metabolic biomarkers for treatment response. Methods Tumor-bearing animals (n = 8 per treatment group) received MK-2206 (120 mg/kg/day) or BEZ235 (50 mg/kg/day) for 3 days. Activity in the PI3K/Akt/mammalian target of rapamycin pathway in xenografts and human biopsies was evaluated using a novel method for semiquantitative assessment of Aktser473 phosphorylation. Metabolic changes were assessed by ex vivo high-resolution magic angle spinning magnetic resonance spectroscopy. Results Using a novel dual near-infrared immunofluorescent imaging method, basal-like xenografts had a 4.5-fold higher baseline level of pAktser473 than luminal-like xenografts. Following treatment, basal-like xenografts demonstrated reduced levels of pAktser473 and decreased proliferation. This correlated with metabolic changes, as both MK-2206 and BEZ235 reduced lactate concentration and increased phosphocholine concentration in the basal-like tumors. BEZ235 also caused increased glucose and glycerophosphocholine concentrations. No response to treatment or change in metabolic profile was seen in luminal-like xenografts. Analyzing tumor sections from five patients with BLBC demonstrated that two of these patients had an elevated pAktser473 level. Conclusion The activity of the PI3K pathway can be determined in tissue sections by quantitative imaging using an antibody towards pAktser473. Long-term treatment with MK-2206 or BEZ235 resulted in significant growth inhibition in basal-like, but not luminal-like, xenografts. This indicates that PI3K inhibitors may have selective efficacy in basal-like breast cancer with increased PI3K signaling, and identifies lactate, phosphocholine and glycerophosphocholine as potential metabolic biomarkers for early therapy monitoring. In human biopsies, variable pAktser473 levels were observed, suggesting heterogeneous PI3K signaling activity in BLBC. PMID:23448424

Institution of basal-bolus therapy at diagnosis for children with type 1 diabetes mellitus.

PubMed

Adhikari, Soumya; Adams-Huet, Beverley; Wang, Yu-Chi A; Marks, James F; White, Perrin C

2009-04-01

We studied whether the institution of basal-bolus therapy immediately after diagnosis improved glycemic control in the first year after diagnosis for children with newly diagnosed type 1 diabetes mellitus. We reviewed the charts of 459 children > or =6 years of age who were diagnosed as having type 1 diabetes between July 1, 2002, and June 30, 2006 (212 treated with basal-bolus therapy and 247 treated with a more-conventional neutral protamine Hagedorn regimen). We abstracted data obtained at diagnosis and at quarterly clinic visits and compared groups by using repeated-measures, mixed-linear model analysis. We also reviewed the records of 198 children with preexisting type 1 diabetes mellitus of >1-year duration who changed from the neutral protamine Hagedorn regimen to a basal-bolus regimen during the review period. Glargine-treated subjects with newly diagnosed diabetes had lower hemoglobin A1c levels at 3, 6, 9, and 12 months after diagnosis than did neutral protamine Hagedorn-treated subjects (average hemoglobin A1c levels of 7.05% with glargine and 7.63% with neutral protamine Hagedorn, estimated across months 3, 6, 9, and 12, according to repeated-measures models adjusted for age at diagnosis and baseline hemoglobin A1c levels; treatment difference: 0.58%). Children with long-standing diabetes had no clinically important changes in their hemoglobin A1c levels in the first year after changing regimens. The institution of basal-bolus therapy with insulin glargine at the time of diagnosis of type 1 diabetes was associated with improved glycemic control, in comparison with more-conventional neutral protamine Hagedorn regimens, during the first year after diagnosis.

Cost-effectiveness analysis of IDegLira versus basal-bolus insulin for patients with type 2 diabetes in the Slovak health system

PubMed Central

Psota, Marek; Psenkova, Maria Bucek; Racekova, Natalia; Ramirez de Arellano, Antonio; Vandebrouck, Tom; Hunt, Barnaby

2017-01-01

Aims To investigate the cost-effectiveness of once-daily insulin degludec/liraglutide (IDegLira) versus basal-bolus therapy in patients with type 2 diabetes not meeting glycemic targets on basal insulin from a healthcare payer perspective in Slovakia. Methods Long-term clinical and economic outcomes for patients receiving IDegLira and basal-bolus therapy were estimated using the IMS CORE Diabetes Model based on a published pooled analysis of patient-level data. Results IDegLira was associated with an improvement in quality-adjusted life expectancy of 0.29 quality-adjusted life years (QALYs) compared with basal-bolus therapy. The average lifetime cost per patient in the IDegLira arm was EUR 2,449 higher than in the basal-bolus therapy arm. Increased treatment costs with IDegLira were partially offset by cost savings from avoided diabetes-related complications. IDegLira was highly cost-effective versus basal-bolus therapy with an incremental cost-effectiveness ratio of EUR 8,590 per QALY gained, which is well below the cost-effectiveness threshold set by the law in Slovakia. Conclusion IDegLira is cost-effective in Slovakia, providing a simple option for intensification of basal insulin therapy without increasing the risk of hypoglycemia or weight gain and with fewer daily injections than a basal-bolus regimen. PMID:29276398

Identification of amino acids in the tetratricopeptide repeat and C-terminal domains of protein phosphatase 5 involved in autoinhibition and lipid activation.

PubMed

Kang, H; Sayner, S L; Gross, K L; Russell, L C; Chinkers, M

2001-09-04

Protein phosphatase 5 (PP5) exhibits low basal activity due to the autoinhibitory properties of its N-terminal and C-terminal domains but can be activated approximately 40-fold in vitro by polyunsaturated fatty acids. To identify residues involved in regulating PP5 activity, we performed scanning mutagenesis of its N-terminal tetratricopeptide repeat (TPR) domain and deletion mutagenesis of its C-terminal domain. Mutating residues in a groove of the TPR domain that binds to heat shock protein 90 had no effect on basal phosphatase activity. Mutation of Glu-76, however, whose side chain projects away from this groove, resulted in a 10-fold elevation of basal activity without affecting arachidonic acid-stimulated activity. Thus, the interface of the TPR domain involved in PP5 autoinhibition appears to be different from that involved in heat shock protein 90 binding. We also observed a 10-fold elevation of basal phosphatase activity upon removing the C-terminal 13 amino acids of PP5, with a concomitant 50% decrease in arachidonic acid-stimulated activity. These two effects were accounted for by two distinct amino acid deletions: deleting the four C-terminal residues (496-499) of PP5 had no effect on its activity, but removing Gln-495 elevated basal activity 10-fold. Removal of a further three amino acids had no additional effect, but deleting Asn-491 resulted in a 50% reduction in arachidonic acid-stimulated activity. Thus, Glu-76 in the TPR domain and Gln-495 at the C-terminus were implicated in maintaining the low basal activity of PP5. While the TPR domain alone has been thought to mediate fatty acid activation of PP5, our data suggest that Asn-491, near its C-terminus, may also be involved in this process.

Trastuzumab-Resistant Luminal B Breast Cancer Cells Show Basal-Like Cell Growth Features Through NF-κB-Activation

PubMed Central

Kanzaki, Hirotaka; Mukhopadhya, Nishit K.; Cui, Xiaojiang; Ramanujan, V. Krishnan

2016-01-01

A major clinical problem in the treatment of breast cancer is mortality due to metastasis. Understanding the molecular mechanisms associated with metastasis should aid in designing new therapeutic approaches for breast cancer. Trastuzumab is the main therapeutic option for HER2+ breast cancer patients; however, the molecular basis for trastuzumab resistance (TZR) and subsequent metastasis is not known. Earlier, we found expression of basal-like molecular markers in TZR tissues from patients with invasive breast cancer.(1) The basal-like phenotype is a particularly aggressive form of breast cancer. This observation suggests that TZR might contribute to an aggressive phenotype. To understand if resistance to TZR can lead to basal-like phenotype, we generated a trastuzumab-resistant human breast cancer cell line (BT-474-R) that maintained human epidermal growth factor receptor 2 (HER2) overexpression and HER2 mediated signaling. Analysis showed that nuclear factor-kappa B (NF-κB) was constitutively activated in the BT-474-R cells, a feature similar to the basal-like tumor phenotype. Pharmacologic inhibition of NF-κB improved sensitivity of BT-474-R cells to trastuzumab. Interestingly, activation of HER2 independent NF-κB is not shown in luminal B breast cancer cells. Our study suggests that by activating the NF-κB pathway, luminal B cells may acquire a HER2+ basal-like phenotype in which NF-κB is constitutively activated; this notion is consistent with the recently proposed “progression through grade” or “evolution of resistance” hypothesis. Furthermore, we identified IKK-α/IKK-β and nuclear accumulation of RelA/p65 as the major determinants in the resistant cells. Thus our study additionally suggests that the nuclear accumulation of p65 may be a useful marker for identifying metastasis-initiating tumor cells and targeting RelA/p65 may limit metastasis of breast and other cancers associated with NF-κB activation. PMID:26871511

Accelerated cell-sheet recovery from a surface successively grafted with polyacrylamide and poly(N-isopropylacrylamide).

PubMed

Akiyama, Yoshikatsu; Kikuchi, Akihiko; Yamato, Masayuki; Okano, Teruo

2014-08-01

A double polymeric nanolayer consisting of poly(N-isopropylacrylamide) (PIPAAm) and hydrophilic polyacrylamide (PAAm) was deposited on tissue culture polystyrene (TCPS) surfaces using electron beam irradiation to form a new temperature-responsive cell culture surface in which the basal hydrophilic PAAm component in the double polymeric layer promotes the hydration of the upper PIPAAm layer and induces rapid cell detachment compared to a conventional temperature-responsive cell culture surface, PIPAAm-grafted TCPS (PIPAAm-TCPS). Take-off angle-dependent X-ray photoelectron spectroscopy spectral analysis demonstrated that the grafted PIPAAm and PAAm components were located in the upper and basal regions of the double polymeric layer, respectively, suggesting that the double polymeric layer forms an inter-penetrating-network-like structure with PAAm at the basal portion of the PIPAAm grafted chains. The wettability of the temperature-responsive cell culture surfaces with the double polymeric layer tended to be more hydrophilic, with an increase in the basal PAAm graft density at a constant PIPAAm graft density. However, when the graft densities of the upper PIPAAm and basal PAAm were optimized, the resulting temperature-responsive cell culture surface with the double polymeric layer exhibited rapid cell detachment while maintaining cell adhesive character comparable to that of PIPAAm-TCPS. The cell adhesive character was altered from cell-adhesive to cell-repellent with increasing PAAm or PIPAAm graft density. The cell adhesive character of the temperature-responsive cell culture surfaces was relatively consistent with their contact angles. These results strongly suggest that the basal PAAm surface properties affect the degree of hydration and dehydration of the subsequently grafted PIPAAm. In addition, the roles of the hydrophilic component in accelerating cell detachment are further discussed in terms of the mobility of the grafted PIPAAm chains. Applications of this insight might be useful for designing temperature-responsive cell culture surfaces for achieving efficient cell culture and quick target cell detachment. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Interindividual differences in stress sensitivity: basal and stress-induced cortisol levels differentially predict neural vigilance processing under stress.

PubMed

Henckens, Marloes J A G; Klumpers, Floris; Everaerd, Daphne; Kooijman, Sabine C; van Wingen, Guido A; Fernández, Guillén

2016-04-01

Stress exposure is known to precipitate psychological disorders. However, large differences exist in how individuals respond to stressful situations. A major marker for stress sensitivity is hypothalamus-pituitary-adrenal (HPA)-axis function. Here, we studied how interindividual variance in both basal cortisol levels and stress-induced cortisol responses predicts differences in neural vigilance processing during stress exposure. Implementing a randomized, counterbalanced, crossover design, 120 healthy male participants were exposed to a stress-induction and control procedure, followed by an emotional perception task (viewing fearful and happy faces) during fMRI scanning. Stress sensitivity was assessed using physiological (salivary cortisol levels) and psychological measures (trait questionnaires). High stress-induced cortisol responses were associated with increased stress sensitivity as assessed by psychological questionnaires, a stronger stress-induced increase in medial temporal activity and greater differential amygdala responses to fearful as opposed to happy faces under control conditions. In contrast, high basal cortisol levels were related to relative stress resilience as reflected by higher extraversion scores, a lower stress-induced increase in amygdala activity and enhanced differential processing of fearful compared with happy faces under stress. These findings seem to reflect a critical role for HPA-axis signaling in stress coping; higher basal levels indicate stress resilience, whereas higher cortisol responsivity to stress might facilitate recovery in those individuals prone to react sensitively to stress. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Knockout silkworms reveal a dispensable role for juvenile hormones in holometabolous life cycle

PubMed Central

Daimon, Takaaki; Uchibori, Miwa; Nakao, Hajime; Sezutsu, Hideki; Shinoda, Tetsuro

2015-01-01

Insect juvenile hormones (JHs) prevent precocious metamorphosis and allow larvae to undergo multiple rounds of status quo molts. However, the roles of JHs during the embryonic and very early larval stages have not been fully understood. We generated and characterized knockout silkworms (Bombyx mori) with null mutations in JH biosynthesis or JH receptor genes using genome-editing tools. We found that embryonic growth and morphogenesis are largely independent of JHs in Bombyx and that, even in the absence of JHs or JH signaling, pupal characters are not formed in first- or second-instar larvae, and precocious metamorphosis is induced after the second instar at the earliest. We also show by mosaic analysis that a pupal specifier gene broad, which is dramatically up-regulated in the late stage of the last larval instar, is essential for pupal commitment in the epidermis. Importantly, the mRNA expression level of broad, which is thought to be repressed by JHs, remained at very low basal levels during the early larval instars of JH-deficient or JH signaling-deficient knockouts. Therefore, our study suggests that the long-accepted paradigm that JHs maintain the juvenile status throughout larval life should be revised because the larval status can be maintained by a JH-independent mechanism in very early larval instars. We propose that the lack of competence for metamorphosis during the early larval stages may result from the absence of an unidentified broad-inducing factor, i.e., a competence factor. PMID:26195792

Knockout silkworms reveal a dispensable role for juvenile hormones in holometabolous life cycle.

PubMed

Daimon, Takaaki; Uchibori, Miwa; Nakao, Hajime; Sezutsu, Hideki; Shinoda, Tetsuro

2015-08-04

Insect juvenile hormones (JHs) prevent precocious metamorphosis and allow larvae to undergo multiple rounds of status quo molts. However, the roles of JHs during the embryonic and very early larval stages have not been fully understood. We generated and characterized knockout silkworms (Bombyx mori) with null mutations in JH biosynthesis or JH receptor genes using genome-editing tools. We found that embryonic growth and morphogenesis are largely independent of JHs in Bombyx and that, even in the absence of JHs or JH signaling, pupal characters are not formed in first- or second-instar larvae, and precocious metamorphosis is induced after the second instar at the earliest. We also show by mosaic analysis that a pupal specifier gene broad, which is dramatically up-regulated in the late stage of the last larval instar, is essential for pupal commitment in the epidermis. Importantly, the mRNA expression level of broad, which is thought to be repressed by JHs, remained at very low basal levels during the early larval instars of JH-deficient or JH signaling-deficient knockouts. Therefore, our study suggests that the long-accepted paradigm that JHs maintain the juvenile status throughout larval life should be revised because the larval status can be maintained by a JH-independent mechanism in very early larval instars. We propose that the lack of competence for metamorphosis during the early larval stages may result from the absence of an unidentified broad-inducing factor, i.e., a competence factor.

Acute impact of home parenteral nutrition in patients with late-stage cancer on family caregivers: preliminary data.

PubMed

Santarpia, Lidia; Bozzetti, Federico

2018-02-01

Since there is no information regarding quality of life of caregivers assisting patients with advanced malignancy on home parenteral nutrition, herewith we report a preliminary series of 19 patients who received total parenteral nutrition at home under the strict supervision of their relatives. The relatives of 19 incurable patients with cancer-related cachexia, discharged from the hospital with a home parenteral nutrition program, were prospectively studied. They filled out a validated questionnaire, the Family Strain Questionnaire Short Form, prior to patient discharge and after 2 weeks of home care. The questionnaire included 30 items, which explored different domains regarding the superimposed burden on caregivers in relation to the assistance given to their relatives. Our findings show that the basal level of strain was relatively high (about three quarters of positive answers) but did not increase after 2 weeks of home care. Similarly, there was no difference in the nutritional status and quality of life of the patients. Eight patients and their relatives could be also analyzed after 2 months and the results maintained unchanged. This preliminary investigation shows that home parenteral nutrition does not exacerbate the level of strain on caregivers involved in surveillance of such a supportive intervention. It is possible that the perception of an active contribution to the benefit of patients, who maintained unchanged their nutritional status and quality of life, could gratify caregivers despite the objective burden in the constant supervision of administering Parenteral Nutrition.

Productive Lifecycle of Human Papillomaviruses that Depends Upon Squamous Epithelial Differentiation

PubMed Central

Kajitani, Naoko; Satsuka, Ayano; Kawate, Akifumi; Sakai, Hiroyuki

2012-01-01

Human papillomaviruses (HPVs) target the stratified epidermis, and can causes diseases ranging from benign condylomas to malignant tumors. Infections of HPVs in the genital tract are among the most common sexually transmitted diseases, and a major risk factor for cervical cancer. The virus targets epithelial cells in the basal layer of the epithelium, while progeny virions egress from terminally differentiated cells in the cornified layer, the surface layer of the epithelium. In infected basal cells, the virus maintains its genomic DNA at low-copy numbers, at which the viral productive lifecycle cannot proceed. Progression of the productive lifecycle requires differentiation of the host cell, indicating that there is tight crosstalk between viral replication and host differentiation programs. In this review, we discuss the regulation of the HPV lifecycle controlled by the differentiation program of the host cells. PMID:22536200

Impact of Basal Conditions on Grounding-Line Retreat

NASA Astrophysics Data System (ADS)

Koellner, S. J.; Parizek, B. R.; Alley, R. B.; Muto, A.; Holschuh, N.; Nowicki, S.

2017-12-01

An often-made assumption included in ice-sheet models used for sea-level projections is that basal rheology is constant throughout the domain of the simulation. The justification in support of this assumption is that physical data for determining basal rheology is limited and a constant basal flow law can adequately approximate current as well as past behavior of an ice-sheet. Prior studies indicate that beneath Thwaites Glacier (TG) there is a ridge-and-valley bedrock structure which likely promotes deformation of soft tills within the troughs and sliding, more akin to creep, over the harder peaks; giving rise to a spatially variable basal flow law. Furthermore, it has been shown that the stability of an outlet glacier varies with the assumed basal rheology, so accurate projections almost certainly need to account for basal conditions. To test the impact of basal conditions on grounding-line evolution forced by ice-shelf perturbations, we modified the PSU 2-D flowline model to enable the inclusion of spatially variable basal rheology along an idealized bedrock profile akin to TG. Synthetic outlet glacier "data" were first generated under steady-state conditions assuming a constant basal flow law and a constant basal friction coefficient field on either a linear or bumpy sloping bed. In following standard procedures, a suite of models were then initialized by assuming different basal rheologies and then determining the basal friction coefficients that produce surface velocities matching those from the synthetic "data". After running each of these to steady state, the standard and full suite of models were forced by drastically reducing ice-shelf buttressing through side-shear and prescribed basal-melting perturbations. In agreement with previous findings, results suggest a more plastic basal flow law enhances stability in response to ice-shelf perturbations by flushing ice from farther upstream to sustain the grounding-zone mass balance required to prolong the current grounding-line position. Mixed rheology beds tend to mimic the retreat of the higher-exponent bed, a behavior enhanced over bumps as the stabilizing ridges tap into ice from local valleys. Thus, accounting for variable basal conditions in ice-sheet model projections is critical for improving both the timing and magnitude of retreat.

Intensity coding in electric hearing: effects of electrode configurations and stimulation waveforms.

PubMed

Chua, Tiffany Elise H; Bachman, Mark; Zeng, Fan-Gang

2011-01-01

Current cochlear implants typically stimulate the auditory nerve with biphasic pulses and monopolar electrode configurations. Tripolar stimulation can increase spatial selectivity and potentially improve place pitch related perception but requires higher current levels to elicit the same loudness as monopolar stimulation. The present study combined delayed pseudomonophonasic pulses, which produce lower thresholds, with tripolar stimulation in an attempt to solve the power-performance tradeoff problem. The present study systematically measured thresholds, dynamic range, loudness growth, and intensity discrimination using either biphasic or delayed pseudomonophonasic pulses under both monopolar and tripolar stimulation. Participants were five Clarion cochlear implant users. For each subject, data from apical, middle, and basal electrode positions were collected when possible. Compared with biphasic pulses, delayed pseudomonophonasic pulses increased the dynamic range by lowering thresholds while maintaining comparable maximum allowable levels under both electrode configurations. However, delayed pseudomonophonasic pulses did not change the shape of loudness growth function and actually increased intensity discrimination limens, especially at lower current levels. The present results indicate that delayed pseudomonophonasic pulses coupled with tripolar stimulation cannot provide significant power savings nor can it increase the functional dynamic range. Whether this combined stimulation could improve functional spectral resolution remains to be seen.

Cholecalciferol administration blunts the systemic renin-angiotensin system in essential hypertensives with hypovitaminosis D.

PubMed

Carrara, Davide; Bernini, Matteo; Bacca, Alessandra; Rugani, Ilaria; Duranti, Emiliano; Virdis, Agostino; Ghiadoni, Lorenzo; Taddei, Stefano; Bernini, Giampaolo

2014-03-01

Vitamin D plasma levels are negatively associated with blood pressure and cardiovascular mortality, and vitamin D supplementation reduces cardiovascular events. Renin-angiotensin system (RAS) suppression may be one of the mechanisms involved. However, there are no interventional prospective studies demonstrating a reduction in circulating RAS components after vitamin D treatment. Fifteen consecutive drug-free patients with essential hypertension and hypovitaminosis D underwent therapy with an oral dose of 25000 I.U. of cholecalciferol once a week for two months, while maintaining a constant-salt diet. In basal conditions and at the end of the study, RAS activity (plasma angiotensinogen, renin, PRA, angiotensin II, aldosterone and urinary angiotensinogen) was investigated, in addition to blood pressure and plasma vitamin D levels (25(OH)D). After cholecalciferol administration, all patients exhibited normalized plasma 25(OH)D values. At the end of the study, a reduction (p < 0.05) in plasma renin and aldosterone, and a decrement, although not significant, of PRA and angiotensin II, was observed. No difference was found in plasma and urinary angiotensinogen or blood pressure values. Our data indicate that in essential hypertensives with hypovitaminosis D, pharmacological correction of vitamin D levels can blunt systemic RAS activity.

Assessment of MRI-Based Marker of Dopaminergic Integrity as a Biological Indicator of Gulf War Illness

DTIC Science & Technology

2016-10-01

including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and...SUBJECT TERMS Gulf war illness; magnetic resonance imaging; dopamine; diffusion tensor imaging 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...nigra, basal ganglia and cortex as markers of integrity of the nigro-striatal dopaminergic pathway using high resolution diffusion tensor imaging (DTI

Not all basal area is created equal: the influence of species and stand development on canopy cover of four common southern pines

Treesearch

David G. Ray

2013-01-01

Restoring natural fire regimes and diverse ground cover to planted or old-field origin southern pine stands typically requires a substantial reduction in overstory density. While maintaining full canopy cover (CC) is consistent with maximizing fiber production, this approach does not allow sufficient light to reach the forest floor to accomplish a broader set of...

Thinning impacts on the resilience of wildlife habitat quality under climate change in coniferous forests of western Oregon

Treesearch

Andrew R. Neill; Klaus J. Puettmann; Adrian Ares

2013-01-01

To understand the impacts of overstory density reductions on resilience of forest ecosystems (i.e., the capacity of an ecosystem to maintain desired ecosystem functions in a fl uctuating environment), we examined overstory basal area and understory vegetation cover and richness collected 6 years after thinning in seven 40- to 60-year-old forests dominated by Douglas-fi...

The effects of partial cutting on stand structure and growth of western hemlock—Sitka spruce stands in southeast Alaska.

Treesearch

Robert L. Deal; John C. Tappeiner

2002-01-01

The effects of partial cutting on species composition, new and residual-tree cohorts, tree size distribution, and tree growth was evaluate on 73 plots in 18 stands throughout southeast Alaska. These partially cut stands were harvested 12-96 years ago, when 16-96% if the former stand basal area was removed.Partial cutting maintained stand structures similar to...

Survey of Basal Stem Rot Disease on Oil Palms (Elaeis guineensis Jacq.) in Kebun Bukit Kijang,North Sumatera, Indonesia

NASA Astrophysics Data System (ADS)

Lisnawita; Hanum, H.; Tantawi, A. R.

2016-08-01

Basal stem rot disease caused by Ganoderma sp. is a significant disease on oil palm plantations in Indonesia, especially in North Sumatera. Currently, the pathogen does not only attack the plants that have produced (old plants) but also attacks the plants that have not produced in the first generation yet. A survey of the distribution of the basal stem rot disease in the plantation of the community has been completed in order to illustrate the distribution and the incidence of the basal stem rot disease in 5 locations of the oil palm plantation of the community in Desa Bukit Kijang, Region of Asahan, North Sumatera, Indonesia. From the research, it is revealed that the basal stem rot disease has spread to all of the observed locations with the level of disease incidence between 0.71% in Kebun Bukit Kijang 3 to 50% in the 17 years old oil palm in Kebun Bukit Kijang 4 and Bukit Kijang 5. The observable symptoms of the basal stem rot disease are chlorotic leaves, the appearance of fruiting body, collapsed plants, and the existence of holes on the basal stem. The incidence of basal stem rot disease is higher on land due to a high sand content (>50%).

Relationship between Increase in Astrocytic GLT-1 Glutamate Transport and Late-LTP

ERIC Educational Resources Information Center

Pita-Almenar, Juan D.; Zou, Shengwei; Colbert, Costa M.; Eskin, Arnold

2012-01-01

Na[superscript +]-dependent high-affinity glutamate transporters have important roles in the maintenance of basal levels of glutamate and clearance of glutamate during synaptic transmission. Interestingly, several studies have shown that basal glutamate transport displays plasticity. Glutamate uptake increases in hippocampal slices during early…

Plasticity of the dense hydrous magnesium silicate phase A at subduction zones conditions

DOE PAGES

Gouriet, K.; Hilairet, N.; Amiguet, E.; ...

2015-09-12

The plasticity of the dense hydrous magnesium silicate (DHMS) phase A, a key hydrous mineral within cold subduction zones, was investigated by two complementary approaches: high-pressure deformation experiments and computational methods. The deformation experiments were carried out at 11 GPa, 400 and 580 °C, with in situ measurements of stress, strain and lattice preferred orientations (LPO). Based on viscoplastic self-consistent modeling (VPSC) of the observed LPO, the deformation mechanisms at 580 °C are consistent with glide on the (0 0 0 1) basal and prismatic planes. At 400 °C the deformation mechanisms involve glide on prismatic, (0 0 0 1)more » basal and pyramidal planes. Both give flow stresses of 2.5–3 GPa at strain rates of 2–4 × 10-5 s-1. We use the Peierls–Nabarro–Galerkin (PNG) approach, relying on first-principles calculations of generalized stacking fault (γ-surface), and model the core structure of potential dislocations in basal and prismatic planes. The computations show multiple dissociations of the and dislocations (⟨a⟩ and ⟨b⟩ dislocations) in the basal plane, which is compatible with the ubiquity of basal slip in the experiments. The γ-surface calculations also suggest and dislocations (⟨a+c⟩ or ⟨c-b⟩ directions) in prismatic and pyramidal planes, which is also consistent with the experimental data. Phase A has a higher flow strength than olivine. When forming at depths from the dehydration of weak and highly anisotropic hydrated ultramafic rocks, phase A may not maintain the mechanical softening antigorite can provide. The seismic properties calculated for moderately deformed aggregates suggest that S-wave seismic anisotropy of phase A-bearing rocks is lower than hydrous subduction zone lithologies such as serpentinites and blueschists.« less

The inclusion of functional foods enriched in fibre, calcium, iodine, fat-soluble vitamins and n-3 fatty acids in a conventional diet improves the nutrient profile according to the Spanish reference intake.

PubMed

Berasategi, Izaskun; Cuervo, Marta; de Las Heras, Arantza Ruiz; Santiago, Susana; Martínez, J Alfredo; Astiasarán, Iciar; Ansorena, Diana

2011-03-01

The growing interest in maintaining good health status through optimal nutrition has boosted the launch of a number of functional foods on the market. The objective of the present study was to theoretically evaluate the nutritional relevance of incorporating selected enriched foods in the diet. A 28 d dietary plan, designed to be balanced under the recommended macronutrients criteria, was used as a basal diet. Some conventional foods were exchanged with foods enriched in fibre, calcium, iodine, vitamins A, D, E or n-3 fatty acids. Nutritional composition of basal and modified diets was derived and compared to the Spanish recommended intakes (RI). The basal diet covered the recommendations for fibre and calcium with mean intake of 28 g and 1241 mg, respectively. The current intake of salt, if iodized, or bread elaborated with this salt, allowed reaching the daily intake of iodine every day, with a mean supply of 216 μg/d and 278 μg/d, respectively. The deficient supply of vitamin E in the basal diet (mean = 8 mg/d) was covered by including enriched margarine and dairy products (mean = 15 mg/d). The low n-3 fatty acids intake in the basal diet (1·1 g/d) increased up to 1·9 g/d after the use of enriched margarine, butter and biscuits and soya drink instead of milk. In order to improve the accomplishment of the RI iodine, vitamin E and n-3 fatty acids, interesting strategies dealing with the incorporation of enriched foods in the diet were successfully initiated.

Comparison of an Electronic Glycemic Management System Versus Provider-Managed Subcutaneous Basal Bolus Insulin Therapy in the Hospital Setting.

PubMed

Aloi, Joseph; Bode, Bruce W; Ullal, Jagdeesh; Chidester, Paul; McFarland, Raymie S; Bedingfield, Amy E; Mabrey, Melanie; Booth, Robby; Mumpower, April; Wallia, Amisha

2017-01-01

American Diabetes Association (ADA) guidelines recommend a basal bolus correction insulin regimen as the preferred method of treatment for non-critically ill hospitalized patients. However, achieving ADA glucose targets safely, without hypoglycemia, is challenging. In this study we evaluated the safety and efficacy of basal bolus subcutaneous (SubQ) insulin therapy managed by providers compared to a nurse-directed Electronic Glycemic Management System (eGMS). This retrospective crossover study evaluated 993 non-ICU patients treated with subcutaneous basal bolus insulin therapy managed by a provider compared to an eGMS. Analysis compared therapy outcomes before Glucommander (BGM), during Glucommander (DGM), and after Glucommander (AGM) for all patients. The blood glucose (BG) target was set at 140-180 mg/dL for all groups. The safety of each was evaluated by the following: (1) BG averages, (2) hypoglycemic events <40 and <70 mg/dL, and (3) percentage of BG in target. Percentage of BG in target was BGM 47%, DGM 62%, and AGM 36%. Patients' BGM BG average was 195 mg/dL, DGM BG average was 169 mg/dL, and AGM BG average was 174 mg/dL. Percentage of hypoglycemic events <70 mg/dL was 2.6% BGM, 1.9% DGM, and 2.8% AGM treatment. Patients using eGMS in the DGM group achieved improved glycemic control with lower incidence of hypoglycemia (<40 mg/dL and <70 mg/dl) compared to both BGM and AGM management with standard treatment. These results suggest that an eGMS can safely maintain glucose control with less hypoglycemia than basal bolus treatment managed by a provider.

Coordination of Septate Junctions Assembly and Completion of Cytokinesis in Proliferative Epithelial Tissues.

PubMed

Daniel, Emeline; Daudé, Marion; Kolotuev, Irina; Charish, Kristi; Auld, Vanessa; Le Borgne, Roland

2018-05-07

How permeability barrier function is maintained when epithelial cells divide is largely unknown. Here, we have investigated how the bicellular septate junctions (BSJs) and tricellular septate junctions (TSJs) are remodeled throughout completion of cytokinesis in Drosophila epithelia. We report that, following cytokinetic ring constriction, the midbody assembles, matures within SJs, and is displaced basally in two phases. In a first slow phase, the neighboring cells remain connected to the dividing cells by means of SJ-containing membrane protrusions pointing to the maturing midbody. Fluorescence recovery after photobleaching (FRAP) experiments revealed that SJs within the membrane protrusions correspond to the old SJs that were present prior to cytokinesis. In contrast, new SJs are assembled below the adherens junctions and spread basally to build a new belt of SJs in a manner analogous to a conveyor belt. Loss of function of a core BSJ component, the Na+/K+-ATPase pump Nervana 2 subunit, revealed that the apical-to-basal spread of BSJs drives the basal displacement of the midbody. In contrast, loss of the TSJ protein Bark beetle indicated that remodeling of TSJs is rate limiting and slowed down midbody migration. In the second phase, once the belt of SJs is assembled, the basal displacement of the midbody is accelerated and ultimately leads to abscission. This last step is temporally uncoupled from the remodeling of SJs. We propose that cytokinesis in epithelia involves the coordinated polarized assembly and remodeling of SJs both in the dividing cell and its neighbors to ensure the maintenance of permeability barrier integrity in proliferative epithelia. Copyright © 2018 Elsevier Ltd. All rights reserved.

Gap junctions and other mechanisms of cell-cell communication regulate basal insulin secretion in the pancreatic islet.

PubMed

Benninger, R K P; Head, W Steven; Zhang, Min; Satin, Leslie S; Piston, David W

2011-11-15

Cell-cell communication in the islet of Langerhans is important for the regulation of insulin secretion. Gap-junctions coordinate oscillations in intracellular free-calcium ([Ca(2+)](i)) and insulin secretion in the islet following elevated glucose. Gap-junctions can also ensure that oscillatory [Ca(2+)](i) ceases when glucose is at a basal levels. We determine the roles of gap-junctions and other cell-cell communication pathways in the suppression of insulin secretion under basal conditions. Metabolic, electrical and insulin secretion levels were measured from islets lacking gap-junction coupling following deletion of connexion36 (Cx36(-/-)), and these results were compared to those obtained using fully isolated β-cells. K(ATP) loss-of-function islets provide a further experimental model to specifically study gap-junction mediated suppression of electrical activity. In isolated β-cells or Cx36(-/-) islets, elevations in [Ca(2+)](i) persisted in a subset of cells even at basal glucose. Isolated β-cells showed elevated insulin secretion at basal glucose; however, insulin secretion from Cx36(-/-) islets was minimally altered. [Ca(2+)](i) was further elevated under basal conditions, but insulin release still suppressed in K(ATP) loss-of-function islets. Forced elevation of cAMP led to PKA-mediated increases in insulin secretion from islets lacking gap-junctions, but not from islets expressing Cx36 gap junctions. We conclude there is a redundancy in how cell-cell communication in the islet suppresses insulin release. Gap junctions suppress cellular heterogeneity and spontaneous [Ca(2+)](i) signals, while other juxtacrine mechanisms, regulated by PKA and glucose, suppress more distal steps in exocytosis. Each mechanism is sufficiently robust to compensate for a loss of the other and still suppress basal insulin secretion.

Effects of Dietary Lycopene Supplementation on Plasma Lipid Profile, Lipid Peroxidation and Antioxidant Defense System in Feedlot Bamei Lamb.

PubMed

Jiang, Hongqin; Wang, Zhenzhen; Ma, Yong; Qu, Yanghua; Lu, Xiaonan; Luo, Hailing

2015-07-01

Lycopene, a red non-provitamin A carotenoid, mainly presenting in tomato and tomato byproducts, has the highest antioxidant activity among carotenoids because of its high number of conjugated double bonds. The objective of this study was to investigate the effect of lycopene supplementation in the diet on plasma lipid profile, lipid peroxidation and antioxidant defense system in feedlot lamb. Twenty-eight Bamei male lambs (90 days old) were divided into four groups and fed a basal diet (LP0, 40:60 roughage: concentrate) or the basal diet supplemented with 50, 100, and 200 mg/kg lycopene. After 120 days of feeding, all lambs were slaughtered and sampled. Dietary lycopene supplementation significantly reduced the levels of plasma total cholesterol (p<0.05, linearly), total triglycerides (TG, p<0.05) and low-density lipoprotein cholesterol (LDL-C, p<0.05), as well as atherogenic index (p<0.001), whereas no change was observed in high-density lipoprotein cholesterol (p>0.05). The levels of TG (p<0.001) and LDL-C (p<0.001) were decreased with the feeding time extension, and both showed a linear trend (p<0.01). Malondialdehyde level in plasma and liver decreased linearly with the increase of lycopene inclusion levels (p<0.01). Dietary lycopene intake linearly increased the plasma antioxidant vitamin E level (p<0.001), total antioxidant capacity (T-AOC, p<0.05), and activities of catalase (CAT, p<0.01), glutathione peroxidase (GSH-Px, p<0.05) and superoxide dismutase (SOD, p<0.05). The plasma T-AOC and activities of GSH-Px and SOD decreased with the extension of the feeding time. In liver, dietary lycopene inclusion showed similar antioxidant effects with respect to activities of CAT (p<0.05, linearly) and SOD (p<0.001, linearly). Therefore, it was concluded that lycopene supplementation improved the antioxidant status of the lamb and optimized the plasma lipid profile, the dosage of 200 mg lycopene/kg feed might be desirable for growing lambs to prevent environment stress and maintain normal physiological metabolism.

Production of jet fuel precursor monoterpenoids from engineered Escherichia coli.

PubMed

Mendez-Perez, Daniel; Alonso-Gutierrez, Jorge; Hu, Qijun; Molinas, Margaux; Baidoo, Edward E K; Wang, George; Chan, Leanne J G; Adams, Paul D; Petzold, Christopher J; Keasling, Jay D; Lee, Taek S

2017-08-01

Monoterpenes (C 10 isoprenoids) are the main components of essential oils and are possible precursors for many commodity chemicals and high energy density fuels. Monoterpenes are synthesized from geranyl diphosphate (GPP), which is also the precursor for the biosynthesis of farnesyl diphosphate (FPP). FPP biosynthesis diverts the carbon flux from monoterpene production to C 15 products and quinone biosynthesis. In this study, we tested a chromosomal mutation of Escherichia coli's native FPP synthase (IspA) to improve GPP availability for the production of monoterpenes using a heterologous mevalonate pathway. Monoterpene production at high levels required not only optimization of GPP production but also a basal level of FPP to maintain growth. The optimized strains produced two jet fuel precursor monoterpenoids 1,8-cineole and linalool at the titer of 653 mg/L and 505 mg/L, respectively, in batch cultures with 1% glucose. The engineered strains developed in this work provide useful resources for the production of high-value monoterpenes. Biotechnol. Bioeng. 2017;114: 1703-1712. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

ALD1 Regulates Basal Immune Components and Early Inducible Defense Responses in Arabidopsis.

PubMed

Cecchini, Nicolás M; Jung, Ho Won; Engle, Nancy L; Tschaplinski, Timothy J; Greenberg, Jean T

2015-04-01

Robust immunity requires basal defense machinery to mediate timely responses and feedback cycles to amplify defenses against potentially spreading infections. AGD2-LIKE DEFENSE RESPONSE PROTEIN 1 (ALD1) is needed for the accumulation of the plant defense signal salicylic acid (SA) during the first hours after infection with the pathogen Pseudomonas syringae and is also upregulated by infection and SA. ALD1 is an aminotransferase with multiple substrates and products in vitro. Pipecolic acid (Pip) is an ALD1-dependent bioactive product induced by P. syringae. Here, we addressed roles of ALD1 in mediating defense amplification as well as the levels and responses of basal defense machinery. ALD1 needs immune components PAD4 and ICS1 (an SA synthesis enzyme) to confer disease resistance, possibly through a transcriptional amplification loop between them. Furthermore, ALD1 affects basal defense by controlling microbial-associated molecular pattern (MAMP) receptor levels and responsiveness. Vascular exudates from uninfected ALD1-overexpressing plants confer local immunity to the wild type and ald1 mutants yet are not enriched for Pip. We infer that, in addition to affecting Pip accumulation, ALD1 produces non-Pip metabolites that play roles in immunity. Thus, distinct metabolite signals controlled by the same enzyme affect basal and early defenses versus later defense responses, respectively.

Effects of irradiated Ergosan on the growth performance and mucus biological components of rainbow trout Oncorhynchus mykiss

NASA Astrophysics Data System (ADS)

Sheikhzadeh, Najmeh; Chehrara, Fatemeh; Heidarieh, Marzieh; Nofouzi, Katayoon; Baradaran, Behzad

2016-01-01

Effects of irradiated and non-irradiated Ergosan extract (alginic acid) on rainbow trout growth performance and skin mucosal immunity were compared. Ergosan was irradiated at 30 kGy in a cobalt-60 irradiator. A total of 252 fish (128.03±9.4 g) were randomly divided into four equal groups, given the basal diet either unsupplemented with Ergosan (control group) or supplemented with crude Ergosan (5 g/kg), ethanol-extracted Ergosan (0.33 g/kg) or irradiated Ergosan (0.33 g/kg) according to this protocol: basal diet for 15 days, treatment diet for 15 days, basal diet for 10 days and treatment diet for 15 days. Highest growth performance was observed in fish fed irradiated Ergosan ( P <0.05). Dietary administration of different Ergosan types did not cause any changes in mucus protein level, but improved alkaline phosphatase level and hemagglutination titer compared with the control (basal diet without Ergosan) on day 55 of feeding trial ( P <0.05). Furthermore, the highest value of lysozyme activity was observed in gamma-irradiated Ergosan on day 55. In conclusion, gamma-irradiated Ergosan at 0.33 g/kg was found to improve growth performance and mucus biological components significantly in comparison with the control group (basal diet without Ergosan).

SLC20A2 DEFICIENCY IN MICE LEADS TO ELEVATED PHOSPHATE LEVELS IN CEREBROSPINAL FLUID AND GLYMPHATIC PATHWAY-ASSOCIATED ARTERIOLAR CALCIFICATION, AND RECAPITULATES HUMAN IDIOPATHIC BASAL GANGLIA CALCIFICATION

PubMed Central

Wallingford, MC; Chia, J; Leaf, EM; Borgeia, S; Chavkin, NW; Sawangmake, C; Marro, K; Cox, TC; Speer, MY; Giachelli, CM

2016-01-01

Idiopathic basal ganglia calcification is a brain calcification disorder that has been genetically linked to autosomal dominant mutations in the sodium-dependent phosphate co-transporter, SLC20A2. The mechanisms whereby deficiency of Slc20a2 leads to basal ganglion calcification are unknown. In the mouse brain, we found that Slc20a2 was expressed in tissues that produce and/or regulate cerebrospinal fluid, including choroid plexus, ependyma and arteriolar smooth muscle cells. Haploinsufficient Slc20a2 +/− mice developed age-dependent basal ganglia calcification that formed in glymphatic pathway-associated arterioles. Slc20a2 deficiency uncovered phosphate homeostasis dysregulation characterized by abnormally high cerebrospinal fluid phosphate levels and hydrocephalus, in addition to basal ganglia calcification. Slc20a2 siRNA knockdown in smooth muscle cells revealed increased susceptibility to high phosphate-induced calcification. These data suggested that loss of Slc20a2 led to dysregulated phosphate homeostasis and enhanced susceptibility of arteriolar smooth muscle cells to elevated phosphate-induced calcification. Together, dysregulated cerebrospinal fluid phosphate and enhanced smooth muscle cell susceptibility may predispose to glymphatic pathway-associated arteriolar calcification. PMID:26822507

The effect of extra virgin olive oil and soybean on DNA, cytogenicity and some antioxidant enzymes in rats.

PubMed

El-Kholy, Thanaa A; Abu Hilal, Mohammad; Al-Abbadi, Hatim Ali; Serafi, Abdulhalim Salim; Al-Ghamdi, Ahmad K; Sobhy, Hanan M; Richardson, John R C

2014-06-23

We investigated the effect of extra virgin (EV) olive oil and genetically modified (GM) soybean on DNA, cytogenicity and some antioxidant enzymes in rodents. Forty adult male albino rats were used in this study and divided into four groups. The control group of rodents was fed basal ration only. The second group was given basal ration mixed with EV olive oil (30%). The third group was fed basal ration mixed with GM (15%), and the fourth group survived on a combination of EV olive oil, GM and the basal ration for 65 consecutive days. On day 65, blood samples were collected from each rat for antioxidant enzyme analysis. In the group fed on basal ration mixed with GM soyabean (15%), there was a significant increase in serum level of lipid peroxidation, while glutathione transferase decreased significantly. Interestingly, GM soyabean increased not only the percentage of micronucleated polychromatic erythrocytes (MPCE), but also the ratio of polychromatic erythrocytes to normochromatic erythrocytes (PEC/NEC); however, the amount of DNA and NCE were significantly decreased. Importantly, the combination of EV olive oil and GM soyabean significantly altered the tested parameters towards normal levels. This may suggest an important role for EV olive oil on rodents' organs and warrants further investigation in humans.

Basal shuttle of NF-κB/IκBα in resting T lymphocytes regulates HIV-1 LTR dependent expression

PubMed Central

Coiras, Mayte; López-Huertas, María Rosa; Rullas, Joaquín; Mittelbrunn, Maria; Alcamí, José

2007-01-01

Background In HIV-infected T lymphocytes, NF-κB/Rel transcription factors are major elements involved in the activation of LTR-dependent transcription from latency. Most NF-κB heterodimer p65/p50 is sequestered as an inactive form in the cytoplasm of resting T lymphocytes via its interaction with IκB inhibitors. In these cells, both absolute HIV latency and low level ongoing HIV replication have been described. These situations could be related to differences in the balance between NF-κB and IκBα ratio. Actually, control of IκBα by cellular factors such as Murr-1 plays a critical role in maintaining HIV latency in unstimulated T lymphocytes. Formerly, our group demonstrated the presence of nuclear IκBα in T cells after PMA activation. Now we attempt to determine the dynamics of NF-κB/IκBα nucleocytosolic transport in absence of activation as a mechanism to explain both the maintenance of latency and the existence of low level ongoing HIV replication in resting CD4+ T lymphocytes. Results and conclusion We show that the inhibition of the nuclear export by leptomycin B in resting CD4+ T cells resulted in nuclear accumulation of both IκBα and p65/RelA, as well as formation of NF-κB/IκBα complexes. This proves the existence of a rapid shuttling of IκBα between nucleus and cytosol even in absence of cellular activation. The nuclear accumulation of IκBα in resting CD4+ T lymphocytes results in inhibition of HIV-LTR dependent transcription as well as restrains HIV replication in CD4+ T lymphocytes. On the other hand, basal NF-κB activity detected in resting CD4+ T lymphocytes was related to low level HIV replication in these cells. PMID:17686171

Dual specificity phosphatase 5 and 6 are oppositely regulated in human skeletal muscle by acute exercise.

PubMed

Pourteymour, Shirin; Hjorth, Marit; Lee, Sindre; Holen, Torgeir; Langleite, Torgrim M; Jensen, Jørgen; Birkeland, Kåre I; Drevon, Christian A; Eckardt, Kristin

2017-10-01

Physical activity promotes specific adaptations in most tissues including skeletal muscle. Acute exercise activates numerous signaling cascades including pathways involving mitogen-activated protein kinases (MAPKs) such as extracellular signal-regulated kinase (ERK)1/2, which returns to pre-exercise level after exercise. The expression of MAPK phosphatases (MKPs) in human skeletal muscle and their regulation by exercise have not been investigated before. In this study, we used mRNA sequencing to monitor regulation of MKPs in human skeletal muscle after acute cycling. In addition, primary human myotubes were used to gain more insights into the regulation of MKPs. The two ERK1/2-specific MKPs, dual specificity phosphatase 5 (DUSP5) and DUSP6, were the most regulated MKPs in skeletal muscle after acute exercise. DUSP5 expression was ninefold higher immediately after exercise and returned to pre-exercise level within 2 h, whereas DUSP6 expression was reduced by 43% just after exercise and remained below pre-exercise level after 2 h recovery. Cultured myotubes express both MKPs, and incubation with dexamethasone (Dex) mimicked the in vivo expression pattern of DUSP5 and DUSP6 caused by exercise. Using a MAPK kinase inhibitor, we showed that stimulation of ERK1/2 activity by Dex was required for induction of DUSP5 However, maintaining basal ERK1/2 activity was required for basal DUSP6 expression suggesting that the effect of Dex on DUSP6 might involve an ERK1/2-independent mechanism. We conclude that the altered expression of DUSP5 and DUSP6 in skeletal muscle after acute endurance exercise might affect ERK1/2 signaling of importance for adaptations in skeletal muscle during exercise. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

The effect of an adverse psychological environment on salivary cortisol levels in the elderly differs by 5-HTTLPR genotype.

PubMed

Ancelin, Marie-Laure; Scali, Jacqueline; Norton, Joanna; Ritchie, Karen; Dupuy, Anne-Marie; Chaudieu, Isabelle; Ryan, Joanne

2017-12-01

An adverse psychological environment (e.g. stressful events or depression) has been shown to influence basal cortisol levels and cortisol response to stress. This differs depending on the adverse stimuli, but also varies across individuals and may be influenced by genetic predisposition. An insertion/deletion polymorphism in the serotonin transporter gene ( 5-HTTLPR ) is a strong candidate in this regard. To investigate how stressful life events and depression are associated with diurnal cortisol levels in community-dwelling elderly and determine whether this varies according to genetic variability in the 5-HTTLPR . This population-based study included 334 subjects aged 65 and older (mean (SD) = 76.5 (6.3)). Diurnal cortisol was measured on two separate days, under quiet (basal) and stressful conditions. The number of recent major stressful events experienced during the past year was assessed from a 12-item validated questionnaire as an index of cumulative recent stressful events. Lifetime trauma was evaluated using the validated Watson's PTSD inventory, which evaluates the most severe traumatic or frightening experience according to DSM criteria. Depression was defined as having a Mini-International Neuropsychiatric Interview (MINI) diagnosis of current major depressive disorder or high levels of depressive symptoms (Center for Epidemiologic Studies-Depression Scale ≥16). 5-HTTLPR genotyping was performed on blood samples. Exposure to stressful life events was associated with lower basal evening cortisol levels overall, and in the participants with the 5-HTTLPR L allele but not the SS genotype. The greatest effects (over 50% decrease, p < 0.001) were observed for the LL participants having experienced multiple recent stressful events or severe lifetime traumas. Participants with the L allele also had higher evening cortisol stress response. Conversely, depression tended to be associated with a 42% higher basal morning cortisol in the SS participants specifically, but did not modify the association between stressful events and cortisol levels. An adverse psychological environment is associated with basal cortisol levels and cortisol stress response, but this differs according to 5-HTTLPR genotype.

Essential basal cytonemes take up Hedgehog in the Drosophila wing imaginal disc.

PubMed

Chen, Weitao; Huang, Hai; Hatori, Ryo; Kornberg, Thomas B

2017-09-01

Morphogen concentration gradients that extend across developmental fields form by dispersion from source cells. In the Drosophila wing disc, Hedgehog (Hh) produced by posterior compartment cells distributes in a concentration gradient to adjacent cells of the anterior compartment. We monitored Hh:GFP after pulsed expression, and analyzed the movement and colocalization of Hh, Patched (Ptc) and Smoothened (Smo) proteins tagged with GFP or mCherry and expressed at physiological levels from bacterial artificial chromosome transgenes. Hh:GFP moved to basal subcellular locations prior to release from posterior compartment cells that express it, and was taken up by basal cytonemes that extend to the source cells. Hh and Ptc were present in puncta that moved along the basal cytonemes and formed characteristic apical-basal distributions in the anterior compartment cells. The basal cytonemes required diaphanous , SCAR , N euroglian and S ynaptobrevin , and both the Hh gradient and Hh signaling declined under conditions in which the cytonemes were compromised. These findings show that in the wing disc, Hh distributions and signaling are dependent upon basal release and uptake, and on cytoneme-mediated movement. No evidence for apical dispersion was obtained. © 2017. Published by The Company of Biologists Ltd.

The use of the Artelon CMC Spacer for osteoarthritis of the basal joint of the thumb.

PubMed

Richard, Marc J; Lunich, Julie A; Correll, Gretchen R

2014-01-01

Favorable clinical outcomes have been reported with the Artelon CMC Spacer, however, several studies have documented complications with the device. The purpose of this study is to review a single surgeon's experience with the Artelon CMC Spacer for the treatment of basal joint arthritis of the thumb. Five thumbs in 6 patients with symptomatic osteoarthritis of the thumb carpometacarpal (CMC) joint were treated with the Artelon CMC Spacer. The mean age of the patients was 60.8 years old. Patients were followed for a mean of 39.3 months (6-63) post-operatively. Complications occurred in 4 of the 6 thumbs and half of the thumbs required at least one secondary operative procedure. A documented foreign-body reaction was present in 2 of the 6 thumbs. The Artelon CMC Spacer is an interposition material that acts as a biologic spacer for arthritic joints while maintaining mechanical strength. Due to an unacceptably high complication rate, we no longer use the Artelon CMC Spacer for the management of basal joint arthritis of the thumb. 4. Copyright © 2014 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

Real-world clinical responses in patients with type 2 diabetes mellitus adding exenatide BID (EBID) or mealtime insulin to basal insulin: a retrospective study using electronic medical record data.

PubMed

Lang, Kathleen; Nguyen, Hiep; Huang, Huan; Bauer, Elise; Levin, Philip

2018-06-01

Exenatide twice daily (EBID) and mealtime insulin are effective add-on therapies to basal insulin for type 2 diabetes patients in clinical trials. This study used electronic medical record (EMR) data to evaluate analogous real-world clinical responses. Adult patients initiating EBID or mealtime insulin as add-on to basal insulin during January 2008-March 2013 were identified in a US EMR database. EBID patients were propensity score matched 1:1 to mealtime insulin patients. Cohorts were followed for 12 months before (baseline) and 6 months after the index. A1C, hypoglycemic events, change in weight, and other clinical measures were evaluated by A1C attainment level (<6.5, < 7, < 7.5, <8, <9%) and baseline A1C. In total, 1249 EBID patients were matched to 1249 mealtime insulin patients. During follow-up, the percentage reaching A1C levels was similar for EBID vs mealtime insulin cohorts for all attainment levels (<7%: 27.8% vs 24.2%; < 9%: 79.7% vs 79.2%; p = NS). The percentage reaching A1C < 7% was similar for both cohorts with different baseline A1C. EBID patients had less hypoglycemia at all attainment levels (3.1% vs 11.1% [<6.5%]; 2.5% vs 4.7% [<9%]; all p < .03) and more weight loss (-9.0 vs -3.2 lb [<6.5%]; -3.4 vs +0.8 lb [<9%]; all p < .01). EBID added to basal insulin was as effective in a real-world setting as mealtime insulin added to basal insulin in reducing A1C, with less weight gain and less hypoglycemia for a wide range of A1C attainment levels and baseline values.

Transforming growth factor-β signaling: emerging stem cell target in metastatic breast cancer?

PubMed Central

Tan, Antoinette R.; Alexe, Gabriela; Reiss, Michael

2009-01-01

In most human breast cancers, lowering of TGFβ receptor- or Smad gene expression combined with increased levels of TGFβs in the tumor microenvironment is sufficient to abrogate TGFβs tumor suppressive effects and to induce a mesenchymal, motile and invasive phenotype. In genetic mouse models, TGFβ signaling suppresses de novo mammary cancer formation but promotes metastasis of tumors that have broken through TGFβ tumor suppression. In mouse models of “triple-negative” or basal-like breast cancer, treatment with TGFβ neutralizing anti-bodies or receptor kinase inhibitors strongly inhibits development of lung- and bone metastases. These TGFβ antagonists do not significantly affect tumor cell proliferation or apoptosis. Rather, they de-repress anti-tumor immunity, inhibit angiogenesis and reverse the mesenchymal, motile, invasive phenotype characteristic of basal-like and HER2-positive breast cancer cells. Patterns of TGFβ target genes upregulation in human breast cancers suggest that TGFβ may drive tumor progression in estrogen-independent cancer, while it mediates a suppressive host cell response in estrogen-dependent luminal cancers. In addition, TGFβ appears to play a key role in maintaining the mammary epithelial (cancer) stem cell pool, in part by inducing a mesenchymal phenotype, while differentiated, estrogen receptor-positive, luminal cells are unresponsive to TGFβ because the TGFBR2 receptor gene is transcriptionally silent. These same cells respond to estrogen by downregulating TGFβ, while antiestrogens act by upregulating TGFβ. This model predicts that inhibiting TGFβ signaling should drive the differentiation of mammary stem cells into ductal cells. Consequently, TGFβ antagonists may convert basal-like or HER2-positive cancers to a more epithelioid, non-proliferating (and, perhaps, non-metastatic) phenotype. Conversely, these agents might antagonize the therapeutic effects of anti-estrogens in estrogen-dependent luminal cancers. These predictions need to be addressed prospectively in clinical trials and should inform the selection of patient populations most likely to benefit from this novel anti-metastatic therapeutic approach. PMID:18841463

Behaviorally activated mRNA expression profiles produce signatures of learning and enhanced inhibition in aged rats with preserved memory.

PubMed

Haberman, Rebecca P; Colantuoni, Carlo; Koh, Ming Teng; Gallagher, Michela

2013-01-01

Aging is often associated with cognitive decline, but many elderly individuals maintain a high level of function throughout life. Here we studied outbred rats, which also exhibit individual differences across a spectrum of outcomes that includes both preserved and impaired spatial memory. Previous work in this model identified the CA3 subfield of the hippocampus as a region critically affected by age and integral to differing cognitive outcomes. Earlier microarray profiling revealed distinct gene expression profiles in the CA3 region, under basal conditions, for aged rats with intact memory and those with impairment. Because prominent age-related deficits within the CA3 occur during neural encoding of new information, here we used microarray analysis to gain a broad perspective of the aged CA3 transcriptome under activated conditions. Behaviorally-induced CA3 expression profiles differentiated aged rats with intact memory from those with impaired memory. In the activated profile, we observed substantial numbers of genes (greater than 1000) exhibiting increased expression in aged unimpaired rats relative to aged impaired, including many involved in synaptic plasticity and memory mechanisms. This unimpaired aged profile also overlapped significantly with a learning induced gene profile previously acquired in young adults. Alongside the increased transcripts common to both young learning and aged rats with preserved memory, many transcripts behaviorally-activated in the current study had previously been identified as repressed in the aged unimpaired phenotype in basal expression. A further distinct feature of the activated profile of aged rats with intact memory is the increased expression of an ensemble of genes involved in inhibitory synapse function, which could control the phenotype of neural hyperexcitability found in the CA3 region of aged impaired rats. These data support the conclusion that aged subjects with preserved memory recruit adaptive mechanisms to retain tight control over excitability under both basal and activated conditions.

Quantitative imaging of radial oxygen loss from Valisneria spiralis roots with a fluorescent planar optode.

PubMed

Han, Chao; Ren, Jinghua; Tang, Hao; Xu, Di; Xie, Xianchuan

2016-11-01

Oxygen (O2) availability within the sediment-root interface is critical to the survival of macrophytes in O2-deficient sediment; however, our knowledge of the fine-scale impact of macrophyte roots upon the spatiotemporal dynamics of O2 is relatively limited. In this study, a non-invasive imaging technology was utilized to map O2 micro-distribution around Vallisneria spiralis. Long-term imaging results gathered during a 36day-period revealed an abundance of O2 spatiotemporal patterns ranging from 0 to 250μmolL(-1). The root-induced O2 leakage and consequent oxygenated area were stronger in the vicinity of the basal root compared to that found in the root tip. The O2 images revealed V. spiralis exhibited radial O2 loss (ROL) along the entire root, and the O2 distribution along the root length showed a high degree of small-scale spatial heterogeneity decreasing from 80% at the basal root surface to 10% at the root tip. The oxygenated zone area around the roots increased as O2 levels increased with root growth and irradiance intensities ranging from 0 to 216μmol photons m(-2)s(-1). A weak ROL measuring <20% air saturation around the basal root surface was maintained in darkness, which was presumably attributed to the O2 supply from overlying water via plant aerenchyma. The estimated total O2 release to the rhizosphere of V. spiralis was determined to range from 8.80±7.32 to 30.34±17.71nmolm(-2)s(-1), which is much higher than many other macrophyte species. This O2 release may be an important contribution to the high-capacity of V. spiralis for quickly colonizing anaerobic sediment. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluating the influence of National Research Council levels of copper, iron, manganese, and zinc using organic (Bioplex) minerals on resulting tissue mineral concentrations, metallothionein, and liver antioxidant enzymes in grower-finisher swine diets.

PubMed

Gowanlock, D W; Mahan, D C; Jolliff, J S; Hill, G M

2015-03-01

Graded levels of a trace mineral premix containing an organic (Bioplex) source of Cu, Fe, Mn, and Zn was evaluated with additional treatments containing organic Zn or Fe. Grower-finisher pigs were fed from 25 to 115 kg BW. The number of pigs in the experiment, the breeding/genetics of the pigs, the management, and the average age of the pigs were previously reported. The experiment was conducted as a randomized complete block design in 7 replicates. Treatments were 1) basal diet without supplemental Cu, Fe, Mn, and Zn; 2) basal diet + 2.5 mg/kg Cu, 50 mg/kg Fe, 1.5 mg/kg Mn, and 40 mg/kg Zn (50% NRC); 3) basal diet + 5 mg/kg Cu, 100 mg/kg Fe, 3 mg/kg Mn, and 80 mg/kg Zn (100% NRC); 4) basal diet + 25 mg Zn/kg; 5) basal diet + 50 mg Zn/kg; and 6) basal diet + 50 mg Fe/kg. Selenium and I were added to all diets at 0.3 and 0.14 mg/kg, respectively. Diets were composed of corn-soybean meal, dicalcium phosphate, and limestone with phytase added to enhance mineral availability. Three pigs per pen were bled at 55, 80, and 115 kg BW and plasma was analyzed for microminerals. When the average replicate BW was 115 kg, 3 pigs per pen of an equal gender ratio were killed. The liver, kidney, and heart were removed and analyzed for microminerals. Liver, duodenum, and jejunal metallothionein and the antioxidant enzymes in the liver containing these microminerals were determined. The results demonstrated that plasma minerals were unaffected at the 3 BW intervals. Liver and duodenum metallothionein protein were greater ( < 0.05) as dietary micromineral levels increased but jejunum metallothionein did not change as microminerals increased. The activity of Cu/Zn superoxide dismutase (SOD) was not affected as the levels of the micromineral increased, whereas the activity of Mn SOD increased slightly ( < 0.05) to the 50% NRC treatment level. Liver Zn (relative and total) increased ( < 0.05) as dietary micromineral levels increased and also when Zn was added singly to the diet. Liver, kidney, and heart Cu and Mn concentrations were similar at the various micromineral levels. The activities of liver enzymes containing graded levels of Zn were not affected by dietary microminerals at 115 kg BW. These results indicate that the supplemental levels of Cu, Fe, and Mn were not necessary for grower-finisher pigs and that these innate microminerals in a corn-soybean meal diet were adequate, whereas a need for supplemental Zn was demonstrated.

L-Cysteine inhibits root elongation through auxin/PLETHORA and SCR/SHR pathway in Arabidopsis thaliana.

PubMed

Wang, Zhen; Mao, Jie-Li; Zhao, Ying-Jun; Li, Chuan-You; Xiang, Cheng-Bin

2015-02-01

L-Cysteine plays a prominent role in sulfur metabolism of plants. However, its role in root development is largely unknown. Here, we report that L-cysteine reduces primary root growth in a dosage-dependent manner. Elevating cellular L-cysteine level by exposing Arabidopsis thaliana seedlings to high L-cysteine, buthionine sulphoximine, or O-acetylserine leads to altered auxin maximum in root tips, the expression of quiescent center cell marker as well as the decrease of the auxin carriers PIN1, PIN2, PIN3, and PIN7 of primary roots. We also show that high L-cysteine significantly reduces the protein level of two sets of stem cell specific transcription factors PLETHORA1/2 and SCR/SHR. However, L-cysteine does not downregulate the transcript level of PINs, PLTs, or SCR/SHR, suggesting that an uncharacterized post-transcriptional mechanism may regulate the accumulation of PIN, PLT, and SCR/SHR proteins and auxin transport in the root tips. These results suggest that endogenous L-cysteine level acts to maintain root stem cell niche by regulating basal- and auxin-induced expression of PLT1/2 and SCR/SHR. L-Cysteine may serve as a link between sulfate assimilation and auxin in regulating root growth. © 2014 Institute of Botany, Chinese Academy of Sciences.

Monitoring blood glucose levels in female mink during the reproductive cycle: 1. Prevention of hyperglycemia during the nursing period

PubMed Central

Hynes, Amber M.J.; Rouvinen-Watt, Kirsti

2007-01-01

Nursing sickness, the largest cause of death in female adult mink, is a metabolic disorder characterized by hyperglycemia. The impacts of body condition, dietary supplements, and reproductive status on the blood glucose concentration in female mink during the reproductive cycle were investigated. Mink dams on 3 farms were assigned to receive either herring oil (HerO) or chromium picolinate (CrPic) or to be in a control group, receiving only the basal diet, for 6 wk at the onset of lactation. Hyperglycemia was observed throughout the reproductive cycle. Significant differences in blood glucose levels were observed between farms, emphasizing the importance of herd genetics and of animal management and feeding practices in glycemic regulation. Female mink exhibiting hyperglycemia early in the reproductive cycle tended to remain hyperglycemic and to have poorer health and fewer kits. Glucose levels > 7 mmol/L can be considered critical in this regard. Supplementing the diet with CrPic reduced the blood glucose concentration. Results from this study suggest that a diet containing high-quality n-3 polyunsaturated fatty acids, high levels of carbohydrate, and CrPic supplementation may help the nursing mink dam maintain a normal blood glucose concentration during lactation. PMID:17955897

p53 and PCNA Expression in Keratocystic Odontogenic Tumors Compared with Selected Odontogenic Cysts

PubMed Central

Seyedmajidi, Maryam; Nafarzadeh, Shima; Siadati, Sepideh; Shafaee, Shahryar; Bijani, Ali; Keshmiri, Nazanin

2013-01-01

p53 and PCNA expression in keratocystic odontogenic tumors compared with selected odontogenic cysts Summary: The aim of this study was to evaluate p53 and PCNA expression in different odontogenic lesions regarding their different clinical behaviors. Slices prepared from 94 paraffin-embedded tissue blocks (25 radicular cysts (RC), 23 dentigerous cysts (DC), 23 keratocystic odontogenic tumors (KCOT) and 23 calcifying cystic odontogenic tumors (CCOT)) were stained with p53 and PCNA antibodies using immunohistochemistry procedure. The highest level of p53 expression was in the basal layer of RC, and the highest level of PCNA expression was in the suprabasal layer of KCOT. The differences of p53 expression in basal and suprabasal layers as well as PCNA expression in the suprabasal layer were significant but there was no significant difference in PCNA expression in the basal layer of these lesions. The expression of p53 in the basal layer of RC was higher than in other cysts. This may be due to intensive inflammatory infiltration. Also, the high level of PCNA expression in the suprabasal layer of KCOT may justify its neoplastic nature and tendency to recurrence. KCOT and calcifying cystic odontogenic tumors did not show similar expression of studied biomarkers. PMID:24551811

Light Effects on Behavioural Performance Depend on the Individual State of Vigilance

PubMed Central

Barba, Antonio; Padilla, Francisca

2016-01-01

Research has shown that exposure to bright white light or blue-enriched light enhances alertness, but this effect is not consistently observed in tasks demanding high-level cognition (e.g., Sustained Attention to Response Task—SART, which measures inhibitory control). Individual differences in sensitivity to light effects might be mediated by variations in the basal level of arousal. We tested this hypothesis by measuring the participants’ behavioural state of vigilance before light exposure, through the Psychomotor Vigilance Task. Then we compared the effects of a blue-enriched vs. dim light at nighttime on the performance of the auditory SART, by controlling for individual differences in basal arousal. The results replicated the alerting effects of blue-enriched light, as indexed by lower values of both proximal temperature and distal-proximal gradient. The main finding was that lighting effects on SART performance were highly variable across individuals and depended on their prior state of vigilance. Specifically, participants with higher levels of basal vigilance before light exposure benefited most from blue-enriched lighting, responding faster in the SART. These results highlight the importance of considering basal vigilance to define the boundary conditions of light effects on cognitive performance. Our study adds to current research delineating the complex and reciprocal interactions between lighting effects, arousal, cognitive task demands and behavioural performance. PMID:27820822

Light Effects on Behavioural Performance Depend on the Individual State of Vigilance.

PubMed

Correa, Ángel; Barba, Antonio; Padilla, Francisca

2016-01-01

Research has shown that exposure to bright white light or blue-enriched light enhances alertness, but this effect is not consistently observed in tasks demanding high-level cognition (e.g., Sustained Attention to Response Task-SART, which measures inhibitory control). Individual differences in sensitivity to light effects might be mediated by variations in the basal level of arousal. We tested this hypothesis by measuring the participants' behavioural state of vigilance before light exposure, through the Psychomotor Vigilance Task. Then we compared the effects of a blue-enriched vs. dim light at nighttime on the performance of the auditory SART, by controlling for individual differences in basal arousal. The results replicated the alerting effects of blue-enriched light, as indexed by lower values of both proximal temperature and distal-proximal gradient. The main finding was that lighting effects on SART performance were highly variable across individuals and depended on their prior state of vigilance. Specifically, participants with higher levels of basal vigilance before light exposure benefited most from blue-enriched lighting, responding faster in the SART. These results highlight the importance of considering basal vigilance to define the boundary conditions of light effects on cognitive performance. Our study adds to current research delineating the complex and reciprocal interactions between lighting effects, arousal, cognitive task demands and behavioural performance.

Measurement of Lactate Content and Amide Proton Transfer Values in the Basal Ganglia of a Neonatal Piglet Hypoxic-Ischemic Brain Injury Model Using MRI.

PubMed

Zheng, Y; Wang, X-M

2017-04-01

As amide proton transfer imaging is sensitive to protein content and intracellular pH, it has been widely used in the nervous system, including brain tumors and stroke. This work aimed to measure the lactate content and amide proton transfer values in the basal ganglia of a neonatal piglet hypoxic-ischemic brain injury model by using MR spectroscopy and amide proton transfer imaging. From 58 healthy neonatal piglets (3-5 days after birth; weight, 1-1.5 kg) selected initially, 9 piglets remained in the control group and 43 piglets, in the hypoxic-ischemic brain injury group. Single-section amide proton transfer imaging was performed at the coronal level of the basal ganglia. Amide proton transfer values of the bilateral basal ganglia were measured in all piglets. The ROI of MR spectroscopy imaging was the right basal ganglia, and the postprocessing was completed with LCModel software. After hypoxic-ischemic insult, the amide proton transfer values immediately decreased, and at 0-2 hours, they remained at their lowest level. Thereafter, they gradually increased and finally exceeded those of the control group at 48-72 hours. After hypoxic-ischemic insult, the lactate content increased immediately, was maximal at 2-6 hours, and then gradually decreased to the level of the control group. The amide proton transfer values were negatively correlated with lactate content ( r = -0.79, P < .05). This observation suggests that after hypoxic-ischemic insult, the recovery of pH was faster than that of lactate homeostasis. © 2017 by American Journal of Neuroradiology.

Does systemic steroid deficiency affect inner ear functions?

PubMed

Dogan, Remzi; Merıc, Ayşenur; Gedık, Ozge; Tugrul, Selahattin; Eren, Sabri Baki; Ozturan, Orhan

2015-01-01

Today corticosteroids are employed for the treatment of various inner ear disorders. In this study we have investigated probable changes in hearing functions resulting from a deficiency of systemic steroid secretions. Twenty four healthy female rats were used in our study, allocated into three groups (medical adrenalectomy, medical adrenalectomy+dexamethasone, no treatment). Audiological evaluations were conducted at the beginning of the study and on days 7, 14 and 21. Blood samples were taken at the beginning and at the end of the study and blood corticosterone levels were determined. While there were no significant differences between the basal, 7th, 14th and 21st day DPOAE values of group 1, their ABR threshold values showed significant increases. In group 2, there were no significant differences between the basal, 7th, 14th and 21st day DPOAE values. ABR thresholds of group 2 showed significant increases on days 7 and 14 as compared to their basal values, but there were no significant differences between the 21st day and basal ABR threshold values. There were no significant differences between the basal cortisol levels of the three groups. The mean cortisol level of group 1 on day 21 was found to be significantly lower than those of groups 2 and 3. The results of the study demonstrated that there were no significant changes in DPOAE values with the cessation of cortisol secretion, while there was a progressive increase in ABR thresholds, which could be overcome with cortisone replacement. Copyright © 2015 Elsevier Inc. All rights reserved.

Consensus Paper: Towards a Systems-Level View of Cerebellar Function: the Interplay Between Cerebellum, Basal Ganglia, and Cortex.

PubMed

Caligiore, Daniele; Pezzulo, Giovanni; Baldassarre, Gianluca; Bostan, Andreea C; Strick, Peter L; Doya, Kenji; Helmich, Rick C; Dirkx, Michiel; Houk, James; Jörntell, Henrik; Lago-Rodriguez, Angel; Galea, Joseph M; Miall, R Chris; Popa, Traian; Kishore, Asha; Verschure, Paul F M J; Zucca, Riccardo; Herreros, Ivan

2017-02-01

Despite increasing evidence suggesting the cerebellum works in concert with the cortex and basal ganglia, the nature of the reciprocal interactions between these three brain regions remains unclear. This consensus paper gathers diverse recent views on a variety of important roles played by the cerebellum within the cerebello-basal ganglia-thalamo-cortical system across a range of motor and cognitive functions. The paper includes theoretical and empirical contributions, which cover the following topics: recent evidence supporting the dynamical interplay between cerebellum, basal ganglia, and cortical areas in humans and other animals; theoretical neuroscience perspectives and empirical evidence on the reciprocal influences between cerebellum, basal ganglia, and cortex in learning and control processes; and data suggesting possible roles of the cerebellum in basal ganglia movement disorders. Although starting from different backgrounds and dealing with different topics, all the contributors agree that viewing the cerebellum, basal ganglia, and cortex as an integrated system enables us to understand the function of these areas in radically different ways. In addition, there is unanimous consensus between the authors that future experimental and computational work is needed to understand the function of cerebellar-basal ganglia circuitry in both motor and non-motor functions. The paper reports the most advanced perspectives on the role of the cerebellum within the cerebello-basal ganglia-thalamo-cortical system and illustrates other elements of consensus as well as disagreements and open questions in the field.

Mitotic trafficking of silicon microparticles†

PubMed Central

Serda, Rita E.; Ferrati, Silvia; Godin, Biana; Tasciotti, Ennio; Liu, XueWu

2010-01-01

Multistage carriers were recently introduced by our laboratory, with the concurrent objectives of co-localized delivery of multiple therapeutic agents, the “theranostic” integration of bioactive moieties with imaging contrast, and the selective, potentially personalized bypassing of the multiplicity of biological barriers that adversely impact biodistribution of vascularly injected particulates. Mesoporous (“nanoporous”) silicon microparticles were selected as primary carriers in multi-stage devices, with targets including vascular endothelia at pathological lesions. The objective of this study was to evaluate biocompatibility of mesoporous silicon microparticles with endothelial cells using in vitro assays with an emphasis on microparticle compatibility with mitotic events. We observed that vascular endothelial cells, following internalization of silicon microparticles, maintain cellular integrity, as demonstrated by cellular morphology, viability and intact mitotic trafficking of vesicles bearing silicon microparticles. The presence of gold or iron oxide nanoparticles within the porous matrix did not alter the cellular uptake of particles or the viability of endothelial cells subsequent to engulfment of microparticles. Endothelial cells maintained basal levels of IL-6 and IL-8 release in the presence of silicon microparticles. This is the first study that demonstrates polarized, ordered partitioning of endosomes based on tracking microparticles. The finding that mitotic sorting of endosomes is unencumbered by the presence of nanoporous silicon microparticles advocates the use of silicon microparticles for biomedical applications. PMID:20644846

Interaction of basal foliage removal and late season fungicide applications in management of Hop powdery mildew

USDA-ARS?s Scientific Manuscript database

Experiments were conducted over three years to evaluate whether fungicide applications could be ceased after the most susceptible stages of cone development (late July) without unduly affecting crop yield and quality when disease pressure was moderated with varying levels of basal foliage removal. I...

Salt Marsh Formation in the Lower Hudson River Estuary

NASA Technical Reports Server (NTRS)

Merley, Michael; Peteet, Dorothy; Hansen, James E. (Technical Monitor)

2001-01-01

Salt marshes are constant depositional environments and as a result contain accurate indicators of past relative sea level rise and salinity. The Hudson River marshes are at least twice as deep when compared to coastal marshes on either side of the mouth of the Hudson. The reason for this difference in sedimentation is unclear. This study uses macrofossil data as well as sediment stratigraphy in order to understand the formation and evolution of these marshes. The composition of seeds, roots, shoots and foraminifera, are used to indicate past sea levels. The four sites involved in this study are, from south to north, the Arthur Kill Marsh in Staten Island (40 36 N, 74 77W), Piermont marsh (N 4100; 73 55W) Croton Point (41 14 N; 73 50W) and Iona Island (41 18N, 73 58W). These are all tidally influenced but with increasing distances from the New York Bight, which gives a good spectrum of tidal influence. AMS-C14 dates on basal macrofossils will document the time of each marsh formation. Basal material from Arthur Kill (8 m) includes freshwater seeds such as Viola, Potomageton and Alnus along with Salix buds. Basal material from Croton Point (10 m) includes fibrous woody material, foraminifera and Zanichellia seeds and other brackish vegetational components. The basal material from Piermont (13.77 m) is lacking any identifiable macrofossils between 150 and 500 microns. The basal material from Iona Island (10 m) has vegetation such as Scirpus and Cyperus seeds, probably implying a brackish environment. The freshwater origin of the Arthur Kill marsh in Staten Island is significant because it predates either sea level rise or the western channel incision. Additional implications for this study include evidence for changes in river channel geomorphology. Reasons for the relatively deeper river marshes include possible basal clay compaction, high production due to river and marine nutrients as well as tectonic activity. This study provides the groundwork for more high-resolution studies of these marshes to understand the fluctuations in salinity caused by relative sea level rise, tectonic faulting and/or changes in precipitation/evaporation.

Altered cellular magnesium responsiveness to hyperglycemia in hypertensive subjects.

PubMed

Barbagallo, M; Dominguez, L J; Bardicef, O; Resnick, L M

2001-09-01

Previous studies by our group have identified ionic aspects of insulin resistance in hypertension, in which cellular responses to insulin were influenced by the basal intracellular ionic environment-the lower the cytosolic free magnesium (Mg(i)), the less Mg(i) increased following insulin stimulation. To investigate whether this ionic insulin resistance represents a more general abnormality of cellular responsiveness in hypertension, we studied Mg(i) responses to nonhormonal signals such as hyperglycemia (15 mmol/L) and used (31)P-nuclear magnetic resonance (NMR) spectroscopy to measure Mg(i) in erythrocytes from normal (NL, n=14) and hypertensive (HTN, n=12) subjects before and 30, 60, 120, and 180 minutes after in vitro glucose incubations. Basal Mg(i) levels were significantly lower in HTN subjects than in NL subjects (169+/-10 versus 205+/-8 micromol.L(-1), P<0.01). In NL cells, hyperglycemia significantly lowered Mg(i), from 205+/-8 micromol.L(-1) (basal, T=0) to 181+/-8, 162+/-6, 152+/-7, and 175+/-9 micromol.L(-1) (T=30, 60, 120, and 180, respectively; P<0.005 versus T=0 at all times). In HTN cells, maximal Mg(i) responses to hyperglycemia were blunted, from 169+/-10 micromol.L(-1) (basal, T=0) to 170+/-11, 179+/-12, 181+/-14, and 173+/-15 micromol.L(-1) (T=30, 60, 120, and 180, respectively; P=NS versus T=0 at all times). For all subjects, Mg(i) responses to hyperglycemia were closely related to basal Mg(i) levels: the higher the Mg(i), the greater the response (n=26, r=0.620, P<0.001). Thus, (1) erythrocytes from hypertensive vis-à-vis normotensive subjects are resistant to the ionic effects of extracellular hyperglycemia on Mg(i) levels, and (2) cellular ionic responses to glucose depend on the basal Mg(i) environment. Altogether, these data support a role for altered extracellular glucose levels in regulating cellular magnesium metabolism and also suggest the importance of ionic factors in determining cellular responsiveness to nonhormonal as well as hormonal signals.

[Calcitonin physiologically regulates the postmenopausal bone loss and possibly inhibits the bone loss in fast losers].

PubMed

Chen, J T; Shiraki, M; Katase, K; Kato, T; Hirai, Y; Hasumi, K

1994-10-01

To study the correlation between the basal serum calcitonin level and L2-4 bone mineral density (BMD), a cross sectional study of 384 healthy subjects (106 premenopausal, 88 perimenopausal and 109 postmenopausal subjects) and a longitudinal study of 42 oophorectomized subjects were conducted. A positive correlation was found in perimenopause (r = 0.219, p = 0.040) but not in premenopause (r = 0.069, p = 0.4898) and postmenopause (r = 0.141, p = 0.0554) in a cross sectional study. The percent reduction in L2-4BMD compared to the baseline also correlated with preoperative calcitonin levels at 6 months after oophorectomy (r = 0.333, p = 0.0442), but not significantly at 12 months (r = 0.224, p = 0.27). These data suggest that the basal calcitonin level correlates to L2-4BMD only at perimenopause or in the early postoophorectomized period when bone turnover is accelerated and bone resorption seems to be faster than bone formation. In addition the premenopausal basal calcitonin level may be an indicator of the fast loser after menopause.

Metabolite alterations in basal ganglia associated with methamphetamine-related psychiatric symptoms. A proton MRS study.

PubMed

Sekine, Yoshimoto; Minabe, Yoshio; Kawai, Masayoshi; Suzuki, Katsuaki; Iyo, Masaomi; Isoda, Haruo; Sakahara, Harumi; Ashby, Charles R; Takei, Nori; Mori, Norio

2002-09-01

Following the chronic use of methamphetamine, some individuals experience psychosis and anxiety. One reason may be the persistence of metabolite abnormalities in the brain of currently abstinent former methamphetamine users. In this study, N-acetylaspartate (NAA), creatine plus phosphocreatine (Cr+PCr), and choline-containing compound (Cho) levels were measured in the left and right basal ganglia using proton magnetic resonance spectroscopy (MRS) in 13 abstinent methamphetamine users and 11 healthy comparison subjects with no history of illicit drug use. The methamphetamine users showed a significantly reduced Cr+PCr/Cho ratio in the bilateral basal ganglia compared with the healthy comparison subjects. Furthermore, the reduction in the Cr+PCr/Cho ratio was significantly correlated with the duration of methamphetamine use and with the severity of residual psychiatric symptoms. NAA/Cho ratios in the bilateral basal ganglia did not significantly differ between methamphetamine users and comparison subjects. These findings suggest that protracted use of methamphetamine may cause metabolite alterations in the basal ganglia. Furthermore, residual psychiatric symptoms may be attributable to the metabolite alterations in the basal ganglia.

Prostaglandin E2 Adds Bone to a Cancellous Bone Site with a Closed Growth Plate and Low Bone Turnover in Ovariectomized Rats

NASA Technical Reports Server (NTRS)

Ma, Y. F.; Ke, H. Z.; Jee, W. S. S.

1994-01-01

The objects of this study were to determine the responses of a cancellous bone site with a closed growth plate, (the distal tibial metaphysis (DTM), to ovariectomy (OVX) and OVX plus a prostaglandin E(2) treatment, and compare the site's response to previous findings reported for another site, the proximal tibial metaphysis (PTM). Thirty five 3-month old female Sprague-Dawley rats were divided into five groups; basal, sham OVX, and OVX+0, +1, or +6 mg PGE(2)/kg/d injected subcutaneously for 3 months and given double fluorescent labels before sacrifice. Cancellous bone histomorphometric analyses were performed on 20 micrometer thick undecalcified DTM sections. Similar to the PTM, the DTM showed age-related decreases in bone formation and increases in bone resorption, but it differed in that at 3 months POST OVX there was neither bone loss nor changes in formation endpoints. Giving 1 mg PGE(2)/kg/d to OVX rats prevented most age-related changes and maintained the bone formation histomorphometry near basal levels. Treating OVX rats with 6 mg PGE(2)/kd/d prevented age-related bone changes, added extra bone, and improved microanatomical structure by stimulating bone formation, without altering bone resportion. Futhermore, After PGE(2) admimnistration, the DTM, a cancellous bone site with a closed growth plate, increased bone formation more than did the cancellous bone in the PTM.

Prostaglandin E2 Adds Bone to a Cancellous Bone Site with a Closed Growth Plate and Low Bone Turnover in Ovariectomized Rats

NASA Technical Reports Server (NTRS)

Ma, Y. F.; Ke, H. Z.; Jee, W. S. S.

1994-01-01

The objects of this study were to determine the responses of a cancellous bone site with a closed growth plate (the distal tibial metaphysis, DTM) to ovariectomy (OVX) and OVX plus a prostaglandin E2 (PGE2) treatment, and compare the site's response to previous findings reported for another site (the proximal tibial metaphysis, PTM). Thirty-five 3-month old female Sprague-Dawley rats were divided into five groups: basal, sham-OVX, and OVX+0, +1, or +6 mg PGE2/kg/d injected subcutaneously for 3 months and given double fluorescent labels before sacrifice. Cancellous bone histomorphometric analyses were performed on 20-micron-thick undecalcified DTM sections. Similar to the PTM, the DTM showed age-related decreases in bone formation and increases in bone resorption, but it differed in that at 3 months post-OVX; there was neither bone loss nor changes in formation endpoints. Giving 1 mg PGE2/kg/d to OVX rats prevented most age-related changes and maintained the bone formation histomorphometry near basal levels. Treating OVX rats with 6 mg PGE2/kg/d prevented age-related bone changes, added extra bone, and improved microanatomical structure by stimulating bone formation without altering bone resorption. Furthermore, after PGE2 administration, the DTM, a cancellous bone site with a closed growth plate, inereased bone formation more than did the cancellous bone in the PTM.

Intravenously administered oxotremorine and atropine, in doses known to affect pain threshold, affect the intraspinal release of acetylcholine in rats.

PubMed

Abelson, Klas S P; Höglund, A Urban

2002-04-01

Both systemically and intrathecally administered cholinergic agonists produce antinociception while cholinergic antagonists decrease pain threshold. The mechanism and the site of action of these substances are not known. In the present study it was hypothesized that systemically administered muscarinic agonists and antagonists modify nociceptive threshold by affecting intraspinal release of acetylcholine (ACh). Catheters were inserted into the femoral vein in rats maintained on isoflurane anaesthesia for administration of oxotremorine (10-300 microg/kg) and atropine (0.1, 10, 5000 microg/kg). Spinal microdialysis probes were placed intraspinally at approximately the C2-C5 spinal level for sampling of acetylcholine and dialysis delivery of atropine (0.1, 1, 10 nM). Additionally, the tail-flick behaviour was tested on conscious rats injected intraperitoneally with saline, atropine (10, 100 and 5000 microg/kg), or subcutaneously with oxotremorine (30, 100, 300 microg/kg). Subcutaneous administration of oxotremorine (30, 100, 300 microg/kg) significantly increased the tail-flick latency. These doses of oxotremorine dose-dependently increased the intraspinal release of acetylcholine. Intravenously administered atropine, in a dose that produced hyperalgesia (5000 microg/kg) in the tail-flick test, significantly decreased the intraspinal release of acetylcholine. Our results suggest an association between pain threshold and acetylcholine release in spinal cord. It is also suggested that an approximately 30% increase in basal ACh release produces antinociception and that a 30% decrease in basal release produces hyperalgesia.

Caffeine, Adenosine Receptors and Estrogen in Toxin Models of Parkinson’s Disease

DTIC Science & Technology

2009-10-01

including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and...dopaminergic neurotransmission in the basal ganglia,[3] raising the possibility (together with other data [4]) of altered risk for PD in this group. In...receptors could fully account for the hypothesized benefits of A2A antagonists against neurodegeneration in PD. The astrocyte A2A cKO data were

Mapping forest structure and composition from low-density LiDAR for informed forest, fuel, and fire management at Eglin Air Force Base, Florida, USA

Treesearch

Andrew T. Hudak; Benjamin C. Bright; Scott M. Pokswinski; E. Louise Loudermilk; Joseph J. O' Brien; Benjamin S. Hornsby; Carine Klauberg; Carlos A. Silva

2016-01-01

Eglin Air Force Base (AFB) in Florida, in the United States, conserves a large reservoir of native longleaf pine (Pinus palustris Mill.) stands that land managers maintain by using frequent fires. We predicted tree density, basal area, and dominant tree species from 195 forest inventory plots, low-density airborne LiDAR, and Landsat data available across the entirety...

Brush competition retards early stand development of planted ponderosa pine: update on a 24-year study

Treesearch

William W. Oliver

1990-01-01

Growth of ponderosa pine (Pinus ponderosa) was monitored for 24 years after planting at five different square spacings (6, 9. 12, 15, and 18 ft) in the presence or absence of competing brush on the westside Sierra Nevada. Spacing strongly influenced both mean dbh and basal area/ac. In plots maintained free of brush, diameters ranged from 5.1 in. at the 6-ft spacing to...

A Mid-Holocene Relative Sea-Level Stack, New Jersey, USA

NASA Astrophysics Data System (ADS)

Horton, B.; Walker, J. S.; Kemp, A.; Shaw, T. J.; Kopp, R. E.

2017-12-01

Most high resolution (decimeter- and decadal-scale) relative sea-level (RSL) records using salt-marsh microfossils as a proxy only extend through the Common Era, limiting our understanding of driving mechanisms of RSL change and how sea-level is influenced by changing climate. Records beyond the Common Era are limited by the depth of continuous sequences of salt-marsh peat suitable for high resolution reconstructions, as well as contamination by local processes such as sediment compaction. In contrast, sequences of basal peats have produced compaction-free RSL records through the Holocene, but at a low resolution (meter- and centennial-scale). We devise a new Multi-Proxy Presence/Absence Method (MP2AM) to develop a mid-Holocene RSL stack. We stack a series of 1 m basal peat cores that overlap along a uniform elevational gradient above an incompressible basal sand. We analyzed three sea-level indicators from 14 cores: foraminifera, testate amoebae, and stable carbon isotope geochemistry. To reconstruct RSL, this multi-proxy approach uses the timesaving presence/absence of forams and testates to determine the elevation of the highest occurrence of forams and the lowest occurrence of testates in each basal core. We use stable carbon isotope geochemistry to determine the C3/C4 vegetation boundary in each core. We develop age-depth models for each core using a series of radiocarbon dates. The RSL records from each 1 m basal core are combined to create a stack or, in effect, one long core of salt-marsh material. This method removes the issue of compaction to create a continuous RSL record to address temporal changes and periods of climate and sea-level variability. We reconstruct a southern NJ mid-Holocene RSL record from Edwin B. Forsythe National Wildlife Refuge, where Kemp et al. (2013) completed a 2500 yr RSL record using a foraminifera-based transfer function approach. Preliminary radiocarbon dates suggest the basal sequence is at least 4246-4408 cal yrs BP. Presence/absence of forams and testates and the transition of C3/C4 vegetation is identified in each core and constrained with radiocarbon dating. A short core with full counts of forams and testates is used to test the new method and compare with the traditional foraminifera-based transfer function approach and the local tide gauge record.

Tazarotene-induced gene 3 is suppressed in basal cell carcinomas and reversed in vivo by tazarotene application.

PubMed

Duvic, Madeleine; Ni, Xiao; Talpur, Rakhashandra; Herne, Kelly; Schulz, Claudia; Sui, Dawen; Ward, Staci; Joseph, Aaron; Hazarika, Parul

2003-10-01

Basal cell carcinomas are the most common form of skin cancer. Tazarotene is a retinoic acid receptor selective retinoid that upregulates a tumor suppressor, tazarotene-induced gene 3 (TIG-3), in keratinocytes and psoriasis. Expression of TIG-3 in basal cell carcinomas was studied in an opened-label pilot biomarker study of 22 patients with basal cell carcinomas who applied tazarotene 0.1% gel for up to 12 wk prior to excision. Nineteen paired baseline and treated specimens were compared using immunohistochemistry and in situ hybridization. Compared to overlying normal epidermis, TIG-3 protein and mRNA were decreased in 14 and 18 of 19 basal cell carcinomas (74% and 95%), respectively (p < 0.001). Tazarotene treatment was associated with increased TIG-3 protein and mRNA expression in basal cell carcinomas compared to baseline levels (p < or = 0.001 and p = 0.028, respectively). Sixty percent of basal cell carcinomas treated with tazarotene decreased in size by at least 25%. Ten of 19 lesions improved histologically, including three complete responses. There was a correlation between the increased expression of TIG-3 protein and histologic improvement (p = 0.020), suggesting that suppression of TIG-3 may underlie the development of basal cell carcinomas. This association suggests that reversal of TIG-3 expression may help to explain the mechanism of retinoid action in epidermal differentiation and chemoprevention.

Postnatal handling does not normalize hypothalamic corticotropin-releasing factor mRNA levels in animals prenatally exposed to ethanol.

PubMed

Gabriel, Kara I; Glavas, Maria M; Ellis, Linda; Weinberg, Joanne

2005-06-09

Postnatal handling has been shown to attenuate some of the deficits in developmental outcome observed following prenatal ethanol exposure (E) although it appears to be ineffective at ameliorating the hypothalamic-pituitary-adrenal (HPA) hyperresponsiveness to stressors that has been observed in adult E animals. However, the effects of postnatal handling on central regulation of HPA activity in E animals, particularly with regard to alterations in steady-state hypothalamic corticotropin-releasing factor (CRF) activity, have not been examined. In the present study, offspring from E, pair-fed (PF), and ad-libitum-fed control (C) groups were exposed to daily handling during the first 2 weeks of life (H) or were left entirely undisturbed until weaning (NH). Basal CRF and arginine vasopressin (AVP) mRNA in the parvocellular portion of the paraventricular nucleus (pPVN) of the hypothalamus were assessed at 90-110 days of age. Prenatal ethanol exposure resulted in elevated basal pPVN CRF mRNA levels compared to those in ad-libitum-fed controls. Handling altered CRF mRNA levels in a sex-specific and prenatal treatment-specific manner. Females showed no significant effects of handling. In contrast, handling decreased CRF mRNA levels in PF and C but not E males compared to their NH counterparts. There were no effects of prenatal ethanol or postnatal handling on AVP mRNA levels. These findings indicate that prenatal ethanol exposure results in elevated basal CRF mRNA levels in adulthood and that handling appears to be ineffective in normalizing those elevations, supporting the suggestion that altered basal HPA regulation in E animals may, at least in part, underlie their HPA hyperresponsiveness to stressors.

Anandamide enhances extracellular levels of adenosine and induces sleep: an in vivo microdialysis study.

PubMed

Murillo-Rodriguez, Eric; Blanco-Centurion, Carlos; Sanchez, Cristina; Piomelli, Daniele; Shiromani, Priyattam J

2003-12-15

The principal component of marijuana, delta-9-tetrahydrocannabinol increases sleep in humans. Endogenous cannabinoids, such as N-arachidonoylethanolamine (anandamide), also increase sleep. However, the mechanism by which these molecules promote sleep is not known but might involve a sleep-inducing molecule such as adenosine. Microdialysis samples were collected from the basal forebrain in order to detect levels of adenosine before and after injection of anandamide. Rats were implanted for sleep studies, and a cannula was placed in the basal forebrain to collect microdialysis samples. Samples were analyzed using high-performance liquid chromatography. Basic neuroscience research laboratory. Three-month-old male F344 rats. At the start of the lights-on period, animals received systemic injections of dimethyl sulfoxide (vehicle), anandamide, SR141716A (cannabinoid receptor 1 [CB1] antagonist), or SR141716A and anandamide. One hour after injections, microdialysis samples were collected (5 microL) from the basal forebrain every hour over a 20-minute period for 5 hours. The samples were immediately analyzed via high-performance liquid chromatography for adenosine levels. Sleep was also recorded continuously over the same period. Anandamide increased adenosine levels compared to vehicle controls with the peak levels being reached during the third hour after drug injection. There was a significant increase in slow-wave sleep during the third hour. The induction in sleep and the rise in adenosine were blocked by the CB1-receptor antagonist, SR141716A. Anandamide increased adenosine levels in the basal forebrain and also increased sleep. The soporific effects of anandamide were mediated by the CB1 receptor, since the effects were blocked by the CB1-receptor antagonist. These findings identify a potential therapeutic use of endocannabinoids to induce sleep in conditions where sleep may be severely attenuated.

Noninvasive assessment of myocardial mechanics of the left ventricle in rabbits using velocity vector imaging.

PubMed

Zhou, Jia; Pu, Da-Rong; Tian, Lei-Qi; Tong, Hai; Liu, Hong-Yu; Tang, Yan; Zhou, Qi-Chang

2015-05-28

Our study aimed to investigate the feasibility of velocity vector imaging (VVI) to analyze left ventricular (LV) myocardial mechanics in rabbits at basal state. The animals used in this study were 30 New Zealand white rabbits. All rabbits underwent routine echocardiography under VVI-mode at basal state. The 2-dimensional (2-D) echocardiography images acquired included parasternal left long-axis views and short-axis views at the level of LV mitral valve, papillary muscles, and apex. Images were analyzed by VVI software. At basal state, longitudinal LV velocity decreased from the basal to the apical segment (P<0.05). In the short axis direction, the highest peak myocardial velocity was found between the anterior septum and anterior wall for each segment at the same level; the peak strains and strain rates (SR) were the highest in the anterior and lateral wall compared to other segments (all P<0.05). During systole, LV base rotated in a clockwise direction and LV apex rotated in a counter-clockwise direction, while during diastole, both LV base and apex rotated in the direction opposite to systole. The rotation angle, rotation velocity and unwinding velocity in the apical segment were greater than the basal segment (P<0.05). VVI is a reliable tool for evaluating LV myocardial mechanics in rabbits at basal state, and the LV long-axis short-axis and torsional motions reflect the normal regular patterns. Our study lays the foundation for future experimental approaches in rabbit models and for other applications related to the study of human myocardial mechanics.

Evaluation of Physical Examination Tests for Thumb Basal Joint Osteoarthritis

PubMed Central

Model, Zina; Liu, Andrew Y.; Kang, Lana; Wolfe, Scott W.; Burket, Jayme C.; Lee, Steve K.

2016-01-01

Background: We compare the ability of 3 diagnostic tests to reproduce the pain of basilar joint arthritis (BJA): the grind test, the lever test (grasping the first metacarpal just distal to the basal joint and shucking back and forth in radial and ulnar directions), and the metacarpophalangeal extension test. Methods: Sixty-two patients with thumb BJA were enrolled. The 3 tests were performed in a random order on both hands of each patient. Prior to testing, patients reported their typical pain level and subsequently rated their pain after each test on a 0 to 10 scale, also specifying the extent to which the test reproduced their thumb pain (fully, partially, not at all). All patients had radiographs that displayed basal joint arthritis. A test was defined as positive for BJA if pain produced was greater than 0. Sensitivity and specificity for each test were calculated using the patients’ history of pain localized to the basal joint and BJA diagnosis on radiographs as the gold standard. Results: The lever test produced the greatest level of pain and best reproduced the presenting pain. The lever test also had the highest sensitivity, high specificity, and the lowest false-negative rate. The grind test had the lowest sensitivity, highest specificity, and highest false-negative rate. Conclusions: The lever test was the diagnostic test that best reproduced the pain caused by thumb basal joint osteoarthritis. We recommend using the lever physical examination test when evaluating the patient with suspected basal joint osteoarthritis. The often-quoted grind test is of limited diagnostic value. PMID:27418899

Stimulation of the substantia nigra influences the specification of memory-guided saccades

PubMed Central

Mahamed, Safraaz; Garrison, Tiffany J.; Shires, Joel

2013-01-01

In the absence of sensory information, we rely on past experience or memories to guide our actions. Because previous experimental and clinical reports implicate basal ganglia nuclei in the generation of movement in the absence of sensory stimuli, we ask here whether one output nucleus of the basal ganglia, the substantia nigra pars reticulata (nigra), influences the specification of an eye movement in the absence of sensory information to guide the movement. We manipulated the level of activity of neurons in the nigra by introducing electrical stimulation to the nigra at different time intervals while monkeys made saccades to different locations in two conditions: one in which the target location remained visible and a second in which the target location appeared only briefly, requiring information stored in memory to specify the movement. Electrical manipulation of the nigra occurring during the delay period of the task, when information about the target was maintained in memory, altered the direction and the occurrence of subsequent saccades. Stimulation during other intervals of the memory task or during the delay period of the visually guided saccade task had less effect on eye movements. On stimulated trials, and only when the visual stimulus was absent, monkeys occasionally (∼20% of the time) failed to make saccades. When monkeys made saccades in the absence of a visual stimulus, stimulation of the nigra resulted in a rotation of the endpoints ipsilaterally (∼2°) and increased the reaction time of contralaterally directed saccades. When the visual stimulus was present, stimulation of the nigra resulted in no significant rotation and decreased the reaction time of contralaterally directed saccades slightly. Based on these measurements, stimulation during the delay period of the memory-guided saccade task influenced the metrics of saccades much more than did stimulation during the same period of the visually guided saccade task. Because these effects occurred with manipulation of nigral activity well before the initiation of saccades and in trials in which the visual stimulus was absent, we conclude that information from the basal ganglia influences the specification of an action as it is evolving primarily during performance of memory-guided saccades. When visual information is available to guide the specification of the saccade, as occurs during visually guided saccades, basal ganglia information is less influential. PMID:24259551

The Cerebellum and Its Wrapping Meninge: Developmental Interplay between Two Major Structures.

PubMed

Catala, Martin

2017-10-01

Meninges have long been considered as a protective and supportive tissue for the central nervous system. Nevertheless, new developmental roles are now attributed to them. The meninges that surround the cerebellum come from the cephalic mesoderm. They are essential for the cerebellum to develop normally. They induce and maintain the basal lamina and glia limitans. In the absence of these structures, the external granular cells of the cerebellum migrate aberrantly and penetrate the subarachnoid space. The molecules involved in the recognition between the cerebellar primordium and the basal lamina belong to two groups in humans: dystroglycan and laminin on the one hand, and GPR56 and collagen III on the other. Finally, molecules secreted by the meninges and acting on the cerebellum begin to be demonstrated; such is the case of SDF1 secreted under the action of FOXC1. Georg Thieme Verlag KG Stuttgart · New York.

Pharyngeal satellite cells undergo myogenesis under basal conditions and are required for pharyngeal muscle maintenance

PubMed Central

Randolph, Matthew E.; Phillips, Brittany L.; Choo, Hyo-Jung; Vest, Katherine E.; Vera, Yandery; Pavlath, Grace K.

2015-01-01

The pharyngeal muscles of the nasal, oral, and laryngeal pharynxes are required for swallowing. Pharyngeal muscles are preferentially affected in some muscular dystrophies yet spared in others. Muscle stem cells, called satellite cells, may be critical factors in the development of pharyngeal muscle disorders; however, very little is known about pharyngeal satellite cells (PSC) and their role in pharyngeal muscles. We show that PSC are distinct from the commonly studied hindlimb satellite cells both transcriptionally and biologically. Under basal conditions PSC proliferate, progress through myogenesis, and fuse with pharyngeal myofibers. Furthermore, PSC exhibit biologic differences dependent on anatomic location in the pharynx. Importantly, PSC are required to maintain myofiber size and myonuclear number in pharyngeal myofibers. Together, these results demonstrate that PSC are critical for pharyngeal muscle maintenance and suggest that satellite cell impairment could contribute to pharyngeal muscle pathology associated with various muscular dystrophies and aging. PMID:26178867

The influence of CYP1A2 genotype in the blood pressure response to caffeine ingestion is affected by physical activity status and caffeine consumption level.

PubMed

Soares, Rogerio Nogueira; Schneider, Augusto; Valle, Sandra Costa; Schenkel, Paulo Cavalheiro

2018-03-06

This study aimed to investigate whether the influence of CYP1A2 genotype in the blood pressure (BP) response to caffeine ingestion was affected by physical activity status and habitual caffeine consumption. Thirty-seven participants (19-50 years old) took place in the study and were categorized according to i) genotype: CYP1A2 (AA) "fast metabolizer", and CYP1A2 (AC) "slow metabolizer"; ii) physical activity level: sedentary (S) and physically active (A); and iii) caffeine consumption level: non-habitual caffeine consumer (NC) and habitual heavy caffeine consumer (C). All groups had BP assessed before (basal) and 1 hourh after (post) caffeine ingestion (6 mg·kg -1 ). It was observed that AC genotype individuals had increased basal-DBP and post-caffeine SBP when compared to AA individuals. Additionally, acute caffeine ingestion increased SBP only in the AC group. It was also found that physical activity only modulated the BP responses to acute caffeine ingestion in AC individuals. Furthermore, the results indicated that the habitual heavy caffeine consumers AC individuals had increased basal-DBP when compared to the AA ones. Our results suggest that the influence of CYP1A2 genotype in the basal and post-caffeine BP response to caffeine ingestion is modified by physical activity status and caffeine consumption level. Copyright © 2018 Elsevier Inc. All rights reserved.

Preserved ex vivo inflammatory status and cytokine responses in naturally long-lived mice

PubMed Central

Arranz, Lorena; Lord, Janet M.

2010-01-01

Preserved immune cell function has been reported in mice that achieve extreme longevity. Since cytokines are major modulators of immune responses, we aimed to determine the levels of 21 cytokines secreted ex vivo by peritoneal leukocytes cultured under basal- and mitogen- (conconavalin A (ConA) and LPS) stimulated conditions in middle-aged (44 ± 4 weeks), old (69 ± 4 weeks), very old (92 ± 4 weeks), and extreme long-lived (125 ± 4 weeks) ICR (CD1) female mice. The secretion of cytokines was measured by multiplex luminometry. Increased basal levels of proinflammatory IL-1β, IL-6, IL-12 (p70), IFN-γ, and TNF-α were seen in the old and very old animals, accompanied by decreased IL-10. In contrast, the extreme long-lived mice maintained the overall cytokine profile of middle-aged mice, though the basal secretion of IL-2, IL-9, IL-10, IL-13, and IL-12 (p40) was raised. Under LPS- and/or ConA-stimulated conditions, leukocytes from old and very old animals showed a significantly impaired response with respect to secretion of Th1 cytokines IL-3, IL-12p70, IFN-γ, and TNF-α; Th2 cytokines IL-6, IL-4, IL-10, and IL-13; and the regulatory cytokines IL-2, IL-5, and IL-17. Extreme long-lived mice preserved the middle-aged-like cytokine profile, with the most striking effect seen for the IL-2 response to ConA, which was minimal in the old and very old mice but increased with respect to the middle-aged level in extreme long-lived mice. Chemokine responses in regard to KC, MCP-1, MIP1β, and RANTES were more variable, though similar secretion of LPS-induced KC and MCP-1 and ConA-induced MCP-1, MIP-1β, and RANTES was found in long-lived and middle-aged mice. Thus, extreme long-lived animals showed only a minimal inflammatory profile, much lower than the old and very old groups and also lower than the middle-aged, which is likely mediated by the increase of anti-inflammatory cytokines such as IL-10. This was coupled to a robust response to immune stimuli across an appropriated Th1/Th2 and regulatory cytokine secretion, which seems to be a factor contributing to the preserved immune response reported in very long-lived animals and thus to their extended longevity. PMID:20508994

Effect of dietary taurine supplementation on growth, feed efficiency, and nutrient composition of juvenile sablefish (Anoplopoma fimbria)

USDA-ARS?s Scientific Manuscript database

Juvenile sablefish were fed a low taurine, basal feed with seven graded levels of supplemental taurine to determine taurine requirements for growth and feed efficiency. The basal feed was plant based, formulated primarily with soy and corn proteins with a minimal (9%) amount of fishmeal. The unsuppl...

Increasing Dopamine Levels in the Brain Improves Feedback-Based Procedural Learning in Healthy Participants: An Artificial-Grammar-Learning Experiment

ERIC Educational Resources Information Center

de Vries, Meinou H.; Ulte, Catrin; Zwitserlood, Pienie; Szymanski, Barbara; Knecht, Stefan

2010-01-01

Recently, an increasing number of studies have suggested a role for the basal ganglia and related dopamine inputs in procedural learning, specifically when learning occurs through trial-by-trial feedback (Shohamy, Myers, Kalanithi, & Gluck. (2008). "Basal ganglia and dopamine contributions to probabilistic category learning." "Neuroscience and…

Junior High Basals: Effective Hi/Lo Materials for Remedial High School Readers.

ERIC Educational Resources Information Center

Alvermann, Donna E.

1981-01-01

Discusses the results of an analysis of the appropriateness of eighth-grade basal reading materials for remedial instruction of ninth- and tenth-grade students who read two to three years below grade level. Readability, interest appeal, and representation of content areas are considered. Three data tables and a 14-item reference list are included.…

Ethanol attracts scolytid beetles to Phytophthora ramorum cankers on coast live oak

Treesearch

Rick G. Kelsey; Maia M. Beh; David C. Shaw; Daniel K. Manter

2013-01-01

Ethanol in sapwood was analyzed along vertical transects, through small spot cankers and larger basal cankers, of Phytophthora ramorum-infected stems of Quercus agrifolia at three sites in California. Trees with large basal cankers, known to attract scolytid beetles, had a 4.3 times higher ethanol level than trees with spot cankers...

Nonlinear mixed modeling of basal area growth for shortleaf pine

Treesearch

Chakra B. Budhathoki; Thomas B. Lynch; James M. Guldin

2008-01-01

Mixed model estimation methods were used to fit individual-tree basal area growth models to tree and stand-level measurements available from permanent plots established in naturally regenerated shortleaf pine (Pinus echinata Mill.) even-aged stands in western Arkansas and eastern Oklahoma in the USA. As a part of the development of a comprehensive...

Hedgehog pathway blockade with the cancer drug LDE225 disrupts taste organs and taste sensation.

PubMed

Kumari, Archana; Ermilov, Alexandre N; Allen, Benjamin L; Bradley, Robert M; Dlugosz, Andrzej A; Mistretta, Charlotte M

2015-02-01

Taste sensation on the anterior tongue requires chorda tympani nerve function and connections with continuously renewing taste receptor cells. However, it is unclear which signaling pathways regulate the receptor cells to maintain chorda tympani sensation. Hedgehog (HH) signaling controls cell proliferation and differentiation in numerous tissues and is active in taste papillae and taste buds. In contrast, uncontrolled HH signaling drives tumorigenesis, including the common skin cancer, basal cell carcinoma. Systemic HH pathway inhibitors (HPIs) lead to basal cell carcinoma regression, but these drugs cause severe taste disturbances. We tested the hypothesis that taste disruption by HPIs reflects a direct requirement for HH signaling in maintaining taste organs and gustatory sensation. In mice treated with the HPI LDE225 up to 28 days, HH-responding cells were lost in fungiform papilla epithelium, and papillae acquired a conical apex. Taste buds were either absent or severely reduced in size in more than 90% of aberrant papillae. Taste bud remnants expressed the taste cell marker keratin 8, and papillae retained expression of nerve markers, neurofilament and P2X3. Chorda tympani nerve responses to taste stimuli were markedly reduced or absent in LDE225-treated mice. Responses to touch were retained, however, whereas cold responses were retained after 16 days of treatment but lost after 28 days. These data identify a critical, modality-specific requirement for HH signaling in maintaining taste papillae, taste buds and neurophysiological taste function, supporting the proposition that taste disturbances in HPI-treated patients are an on-target response to HH pathway blockade in taste organs. Copyright © 2015 the American Physiological Society.

Combining Microdialysis and Electrophysiology in Cerebral Cortex to Delineate Functional Implications of Acetylcholine Gradients

NASA Astrophysics Data System (ADS)

Nelson, Kari L.

The neuronal network in cerebral cortex is a dynamic system that can undergo changes in collective neural activity as the organism changes its behavior. For example, during sleep and quiet restful awake state, many neurons tend to fire together in synchrony. In contrast, during alert awake states, firing patterns of neurons tend to be more asynchronous, firing more independently. These changes in population-level synchrony are defined as changes in cortical state. Response to sensory input is state-dependent, i.e., change in cortical state can impact the sensory information processing in cortex and introduce trial-to-trial variability in response to the same repeated stimuli. How the brain maintains reliable perception in spite of such trial-to-trial variability is a longstanding important question in neuroscience research. This dissertation is centered on two hypotheses. The first hypothesis is that different parts of the cortex can be in different states simultaneously. The second hypothesis is that inhomogeneity in cortical states can benefit the system by enabling the cortical network to maintain reliable sensory detection. If one part of the system is in a state that is not good for detection, then another part of the system could be in a different state that is good for detection, thus compensating and maintaining good detection for the system as a whole. These hypotheses were tested on anesthetized rats and awake mice. In anesthetized rats, cholinergic neuromodulation via microdialysis (muD) probes was used to induce cortical state changes in the somatosensory barrel cortex. Changes in cortical state and response to whisker stimulus was recorded with a microelectrode array (MEA). In awake mice, nucleus basalis was optogenetically stimulated by inserting an optic fiber in basal forebrain and response to visual stimulus was analyzed. The results demonstrated heterogeneity in cortical state across the spatial extent of cortical network. Changes in sensory response followed this heterogeneity and sensory detection was not reliable at the level of single neurons or small regions of cortex. The greater population of neurons, on the other hand, maintained reliable sensory detection, suggesting that heterogeneous state can be functionally beneficial for the cortical network.

Basal-topographic control of stationary ponds on a continuously moving landslide

USGS Publications Warehouse

Coe, J.A.; McKenna, J.P.; Godt, J.W.; Baum, R.L.

2009-01-01

The Slumgullion landslide in the San Juan Mountains of southwestern Colorado has been moving for at least the last few hundred years and has multiple ponds on its surface. We have studied eight ponds during 30 trips to the landslide between July 1998 and July 2007. During each trip, we have made observations on the variability in pond locations and water levels, taken ground-based photographs to document pond water with respect to moving landslide material and vegetation, conducted Global Positioning System surveys of the elevations of water levels and mapped pond sediments on the landslide surface. Additionally, we have used stereo aerial photographs taken in October 1939, October 1940 and July 2000 to measure topographic profiles of the eight pond locations, as well as a longitudinal profile along the approximate centerline of the landslide, to examine topographic changes over a 60- to 61-year period of time. Results from field observations, analyses of photographs, mapping and measurements indicate that all pond locations have remained spatially stationary for 60-300 years while landslide material moves through these locations. Water levels during the observation period were sensitive to changes in the local, spring-fed, stream network, and to periodic filling of pond locations by sediment from floods, hyperconcentrated flows, mud flows and debris flows. For pond locations to remain stationary, the locations must mimic depressions along the basal surface of the landslide. The existence of such depressions indicates that the topography of the basal landslide surface is irregular. These results suggest that, for translational landslides that have moved distances larger than the dimensions of the largest basal topographic irregularities (about 200 m at Slumgullion), landslide surface morphology can be used as a guide to the morphology of the basal slip surface. Because basal slip surface morphology can affect landslide stability, kinematic models and stability analyses of translational landslides should attempt to incorporate irregular basal surface topography. Additional implications for moving landslides where basal topography controls surface morphology include the following: dateable sediments or organic material from basal layers of stationary ponds will yield ages that are younger than the date of landslide initiation, and it is probable that other landslide surface features such as faults, streams, springs and sinks are also controlled by basal topography. The longitudinal topographic profile indicated that the upper part of the Slumgullion landslide was depleted at a mean vertical lowering rate of 5.6 cm/yr between 1939 and 2000, while the toe advanced at an average rate of 1.5 m/yr during the same period. Therefore, during this 61-year period, neither the depletion of material at the head of the landslide nor continued growth of the landslide toe has decreased the overall movement rate of the landslide. Continued depletion of the upper part of the landslide, and growth of the toe, should eventually result in stabilization of the landslide. Copyright ?? 2008 John Wiley & Sons, Ltd.

Resveratrol shows vasoprotective effect reducing oxidative stress without affecting metabolic disturbances in insulin-dependent diabetes of rabbits.

PubMed

Akar, Fatma; Pektas, M Bilgehan; Tufan, Can; Soylemez, Selen; Sepici, Aylin; Ulus, A Tulga; Gokalp, Burcu; Ozturk, Kamile; Surucu, H Selcuk

2011-04-01

Resveratrol has been shown to have vasoprotective effects by upregulating oxidative defense mechanisms in a variety of pathophysiological conditions. However, the effect of resveratrol on diabetic oxidative stress and vascular and metabolic abnormalities is not completely understood. Therefore, this study was designed to evaluate whether long-term resveratrol supplementation has a protective effect on vascular function and integrity in association with metabolic parameters and oxidative stress in insulin-dependent diabetes. Diabetes was induced in rabbits with alloxan and maintained for 8 weeks. We used a resveratrol dose of 5 mg/L (10 weeks, starting 14 days before alloxan injection) and 50 mg/L (8 or 10 weeks, starting concomitantly or 14 days before alloxan injection) in the drinking water of rabbits. Relaxation to acetylcholine was impaired (control 75.6 ± 3.59%, versus diabetic 42.23 ± 2.53%) and contractions to phenylephrine increased (control 136.89 ± 2.27%, versus diabetic 159.37 ± 6.27%) in aortas from diabetic animals. These changes were associated with increased basal or NAD(P)H-induced superoxide production, as well as lipid peroxide and superoxide dismutase (SOD) levels in the aortic samples. The maximal relaxation to acetylcholine improved by 75.74 ± 9.04% in diabetic rabbits treated with resveratrol. The increased contractions to phenylephrine were not restored to control values after resveratrol treatments, but sensitivity to the contractions tended to decrease. Resveratrol increased nitrite/nitrate levels and suppressed basal or NAD(P)H-induced superoxide production and lipid peroxide levels in the aortas. Importantly, resveratrol increased serum insulin levels without affecting blood glucose and the lipid profile in diabetic rabbits. Using electron microscopic examinations, resveratrol was found to markedly protect the endothelial integrity from diabetes. Overall, there was no noticeable difference between resveratrol treatment groups on the recovery from diabetes. Our results indicate that resveratrol alleviates type 1 diabetes-induced vasculopathy by decreasing vascular oxidative stress and thereby increasing the bioavailability of nitric oxide without changing metabolic abnormalities.

Influence of immunostimulant polysaccharides, nucleic acids, and Bacillus strains on the innate immune and acute stress response in turbots (Scophthalmus maximus) fed soy bean- and wheat-based diets.

PubMed

Fuchs, V I; Schmidt, J; Slater, M J; Buck, B H; Steinhagen, D

2017-12-01

Immunostimulants are widely applied in aquaculture practice and may have beneficial effects on the immune system and physical functions allowing higher tolerance to stress. In the current study, the impact of four (i-iv) dietary active ingredients on the immune and stress response of turbot was examined in two experiments (I and II). A basal low fish meal (FM; 32%) diet was formulated and supplemented with (i) yeast β-glucan and mannan oligosaccharide (GM), (ii) alginic acid (AC), (iii) yeast nucleotides and RNA (NR), or (iv) Bacillus strains (BS). The basal diet (C-LF) and a high FM (59%) control (C-HF) were maintained. All six diets were fed to juvenile turbots for 84 days in experiment I and for additional 28 days prior to experiment II. Immunological and hematological parameters were determined in experiment I. In experiment II, physical stress response to a typical short-term (<1 day) aquaculture handling procedure (combination of capture, netting/transfer, and crowding) was investigated. For this, turbot blood was sampled before and at 0.5, 1, 4, and 24 h post stress. Plasma lysozyme activity, neutrophil reactive oxygen species (ROS) production, and total plasma protein levels did not significantly differ between treatment groups; however, plasma cholesterol increased significantly in fish fed GM, AC, NR, and C-HF compared to C-LF (I). A significant increase in plasma glucose and triglyceride was observed in GM and NR treatments, while glucose levels were significantly higher in C-HF compared to C-LF. Moreover, the immunostimulant-supplemented diets exhibited significantly lower cortisol levels compared to controls C-LF (at 0.5 h) and C-HF (at 1 h) post stress, respectively (II). According to our findings, FM substitution did not modulate the innate immune response but was associated with reduced levels of cholesterol. Dietary immunostimulants were not effective enough to boost the immune response, but we believe they might be helpful to trigger metabolic advantages during stressful handling events on fish farms.

Spontaneous sleep-wake cycle and sleep deprivation differently induce Bdnf1, Bdnf4 and Bdnf9a DNA methylation and transcripts levels in the basal forebrain and frontal cortex in rats.

PubMed

Ventskovska, Olena; Porkka-Heiskanen, Tarja; Karpova, Nina N

2015-04-01

Brain-derived neurotrophic factor (Bdnf) regulates neuronal plasticity, slow wave activity and sleep homeostasis. Environmental stimuli control Bdnf expression through epigenetic mechanisms, but there are no data on epigenetic regulation of Bdnf by sleep or sleep deprivation. Here we investigated whether 5-methylcytosine (5mC) DNA modification at Bdnf promoters p1, p4 and p9 influences Bdnf1, Bdnf4 and Bdnf9a expression during the normal inactive phase or after sleep deprivation (SD) (3, 6 and 12 h, end-times being ZT3, ZT6 and ZT12) in rats in two brain areas involved in sleep regulation, the basal forebrain and cortex. We found a daytime variation in cortical Bdnf expression: Bdnf1 expression was highest at ZT6 and Bdnf4 lowest at ZT12. Such variation was not observed in the basal forebrain. Also Bdnf p1 and p9 methylation levels differed only in the cortex, while Bdnf p4 methylation did not vary in either area. Factorial analysis revealed that sleep deprivation significantly induced Bdnf1 and Bdnf4 with the similar pattern for Bdnf9a in both basal forebrain and cortex; 12 h of sleep deprivation decreased 5mC levels at the cortical Bdnf p4 and p9. Regression analysis between the 5mC promoter levels and the corresponding Bdnf transcript expression revealed significant negative correlations for the basal forebrain Bdnf1 and cortical Bdnf9a transcripts in only non-deprived rats, while these correlations were lost after sleep deprivation. Our results suggest that Bdnf transcription during the light phase of undisturbed sleep-wake cycle but not after SD is regulated at least partially by brain site-specific DNA methylation. © 2014 European Sleep Research Society.

Involvement of Endogenous Brain-Derived Neurotrophic Factor in Hypothalamic-Pituitary-Adrenal Axis Activity.

PubMed

Naert, G; Zussy, C; Tran Van Ba, C; Chevallier, N; Tang, Y-P; Maurice, T; Givalois, L

2015-11-01

Brain-derived neurotrophic factor (BDNF) appears to be highly involved in hypothalamic-pituitary-adrenal (HPA) axis regulation during adulthood, playing an important role in homeostasis maintenance. The present study aimed to determine the involvement of BDNF in HPA axis activity under basal and stress conditions via partial inhibition of this endogenous neurotrophin. Experiments were conducted in rats and mice with two complementary approaches: (i) BDNF knockdown with stereotaxic delivery of BDNF-specific small interfering RNA (siRNA) into the lateral ventricle of adult male rats and (ii) genetically induced knockdown (KD) of BDNF expression specifically in the central nervous system during the first ontogenesis in mice (KD mice). Delivery of siRNA in the rat brain decreased BDNF levels in the hippocampus (-31%) and hypothalamus (-35%) but not in the amygdala, frontal cortex and pituitary. In addition, siRNA induced no change of the basal HPA axis activity. BDNF siRNA rats exhibited decreased BDNF levels and concomitant altered adrenocortoctrophic hormone (ACTH) and corticosterone responses to restraint stress, suggesting the involvement of BDNF in the HPA axis adaptive response to stress. In KD mice, BDNF levels in the hippocampus and hypothalamus were decreased by 20% in heterozygous and by 60% in homozygous animals compared to wild-type littermates. Although, in heterozygous KD mice, no significant change was observed in the basal levels of plasma ACTH and corticosterone, both hormones were significantly increased in homozygous KD mice, demonstrating that robust cerebral BDNF inhibition (60%) is necessary to affect basal HPA axis activity. All of these results in both rats and mice demonstrate the involvement and importance of a robust endogenous pool of BDNF in basal HPA axis regulation and the pivotal function of de novo BDNF synthesis in the establishment of an adapted response to stress. © 2015 British Society for Neuroendocrinology.

Expression of HtKNOT1, a class I KNOX gene, overlaps cell layers and development compartments of differentiating cells in stems and flowers of Helianthus tuberosus.

PubMed

Michelotti, V; Giorgetti, L; Geri, C; Cionini, G; Pugliesi, C; Fambrini, M

2007-10-01

In plant, post-embryonic development relies on the activities of indeterminate cell populations termed meristems, spatially clustered cell lineages, wherein a subset divides indeterminately. For correct growth, the plant must maintain a constant flow of cells through the meristem, where the input of dividing pluripotent cells offsets the output of differentiating cells. KNOTTED1-like homeobox (KNOX) genes are expressed in specific patterns in the plant meristems and play important roles in maintaining meristematic cell identity. We have analyzed the expression pattern of HtKNOT1, a class I KNOX gene of Helianthus tuberosus, in stems, inflorescence meristems, floral meristems and floral organs. HtKNOT1 is expressed in cambial cells, phloem cells and xylematic parenchyma within apical stem internodes, while in basal internodes HtKNOT1 expression was restricted to the presumptive initials and recently derived phloem cells. In the reproductive phase, HtKNOT1 mRNAs were detected in both the inflorescence and floral meristems as well within lateral organ primordia (i.e. floral bracts, petals, stamens and carpels). In more differentiated flowers, the expression of HtKNOT1 was restricted to developing ovules and pollen mother cells. HtKNOT1 may play a dual role being required to maintain the meristem initials as well as initiating differentiation and/or conferring new cell identity. In particular, it is possible that HtKNOT1 cooperates at floral level with additional factors that more specifically control floral organs and pollen development in H. tuberosus.

Elucidating the Tumor-Suppressive Role of SLITs in Maintaining the Basal Cell Niche

DTIC Science & Technology

2011-10-01

2011) • Discovered Rac as a downstream effector of SLIT/ROBO1 signaling and potential link to Abl signaling in the gland (Macias et al., in preparation...into mechanisms by which normal stem/progenitor cells are regulated, leading to potential insights into how they may be deregulated upon cancerous...of AGMs in breast cancer tumorigenesis and progression and consider their potential in development of new diagnostic markers and therapeutics. AGMs in

Compilation of basal metabolic and blood perfusion rates in various multi-compartment, whole-body thermoregulation models

NASA Astrophysics Data System (ADS)

Shitzer, Avraham; Arens, Edward; Zhang, Hui

2016-07-01

The assignments of basal metabolic rates (BMR), basal cardiac output (BCO), and basal blood perfusion rates (BBPR) were compared in nine multi-compartment, whole-body thermoregulation models. The data are presented at three levels of detail: total body, specific body regions, and regional body tissue layers. Differences in the assignment of these quantities among the compared models increased with the level of detail, in the above order. The ranges of variability in the total body BMR was 6.5 % relative to the lowest value, with a mean of 84.3 ± 2 W, and in the BCO, it was 8 % with a mean of 4.70 ± 0.13 l/min. The least variability among the body regions is seen in the combined torso (shoulders, thorax, and abdomen: ±7.8 % BMR and ±5.9 % BBPR) and in the combined head (head, face, and neck ±9.9 % BMR and ±10.9 % BBPR), determined by the ratio of the standard deviation to the mean. Much more variability is apparent in the extremities with the most showing in the BMR of the feet (±117 %), followed by the BBPR in the arms (±61.3 %). In the tissue layers, most of the bone layers were assigned zero BMR and BBPR, except in the shoulders and in the extremities that were assigned non-zero values in a number of models. The next lowest values were assigned to the fat layers, with occasional zero values. Skin basal values were invariably non-zero but involved very low values in certain models, e.g., BBPR in the feet and the hands. Muscle layers were invariably assigned high values with the highest found in the thorax, abdomen, and legs. The brain, lung, and viscera layers were assigned the highest of all values of both basal quantities with those of the brain layers showing rather tight ranges of variability in both basal quantities. Average basal values of the "time-seasoned" models presented in this study could be useful as a first step in future modeling efforts subject to appropriate adjustment of values to conform to most recently available and reliable data.

Improving the simulation of landfast ice by combining tensile strength and a parameterization for grounded ridges

NASA Astrophysics Data System (ADS)

Lemieux, Jean-François; Dupont, Frédéric; Blain, Philippe; Roy, François; Smith, Gregory C.; Flato, Gregory M.

2016-10-01

In some coastal regions of the Arctic Ocean, grounded ice ridges contribute to stabilizing and maintaining a landfast ice cover. Recently, a grounding scheme representing this effect on sea ice dynamics was introduced and tested in a viscous-plastic sea ice model. This grounding scheme, based on a basal stress parameterization, improves the simulation of landfast ice in many regions such as in the East Siberian Sea, the Laptev Sea, and along the coast of Alaska. Nevertheless, in some regions like the Kara Sea, the area of landfast ice is systematically underestimated. This indicates that another mechanism such as ice arching is at play for maintaining the ice cover fast. To address this problem, the combination of the basal stress parameterization and tensile strength is investigated using a 0.25° Pan-Arctic CICE-NEMO configuration. Both uniaxial and isotropic tensile strengths notably improve the simulation of landfast ice in the Kara Sea but also in the Laptev Sea. However, the simulated landfast ice season for the Kara Sea is too short compared to observations. This is especially obvious for the onset of the landfast ice season which systematically occurs later in the model and with a slower build up. This suggests that improvements to the sea ice thermodynamics could reduce these discrepancies with the data.

Evolution of basal metabolic rate in bank voles from a multidirectional selection experiment.

PubMed

Sadowska, Edyta T; Stawski, Clare; Rudolf, Agata; Dheyongera, Geoffrey; Chrząścik, Katarzyna M; Baliga-Klimczyk, Katarzyna; Koteja, Paweł

2015-05-07

A major theme in evolutionary and ecological physiology of terrestrial vertebrates encompasses the factors underlying the evolution of endothermy in birds and mammals and interspecific variation of basal metabolic rate (BMR). Here, we applied the experimental evolution approach and compared BMR in lines of a wild rodent, the bank vole (Myodes glareolus), selected for 11 generations for: high swim-induced aerobic metabolism (A), ability to maintain body mass on a low-quality herbivorous diet (H) and intensity of predatory behaviour towards crickets (P). Four replicate lines were maintained for each of the selection directions and an unselected control (C). In comparison to C lines, A lines achieved a 49% higher maximum rate of oxygen consumption during swimming, H lines lost 1.3 g less mass in the test with low-quality diet and P lines attacked crickets five times more frequently. BMR was significantly higher in A lines than in C or H lines (60.8, 56.6 and 54.4 ml O2 h(-1), respectively), and the values were intermediate in P lines (59.0 ml O2 h(-1)). Results of the selection experiment provide support for the hypothesis of a positive association between BMR and aerobic exercise performance, but not for the association of adaptation to herbivorous diet with either a high or low BMR. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Treatment Intensification in Type 2 Diabetes: A Real-World Study of 2-OAD Regimens, GLP-1 RAs, or Basal Insulin.

PubMed

Blonde, Lawrence; Raccah, Denis; Lew, Elisheva; Meyers, Juliana; Nikonova, Elena; Ajmera, Mayank; Davis, Keith L; Bertolini, Monica; Guerci, Bruno

2018-06-01

Treatment guidelines recommend a stepwise approach to glycemia management in patients with type 2 diabetes (T2D), but this may result in uncontrolled glycated hemoglobin A1c (HbA1c) between steps. This retrospective analysis compared clinical and economic outcomes among patients with uncontrolled T2D initiating two oral antidiabetes drugs (OADs), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), or basal insulin in a real-world setting. Adults with T2D on OAD monotherapy were identified in the MarketScan claims database (2007-2014). Those initiating two OADs (simultaneously or sequentially), GLP-1 RAs, or basal insulin were selected (date of initiation was termed the 'index date'); patients were required to have HbA1c > 7.0% in the 6 months pre-index date. HbA1c was compared from 6 months pre- to 1-year post-index. Annual all-cause healthcare utilization and costs were reported over the 1-year follow-up period. Data for 6054 patients were analyzed (2-OAD, n = 4442; GLP-1 RA, n = 361; basal insulin, n = 1251). Baseline HbA1c was high in all cohorts, but highest in the basal-insulin cohort. Treatment initiation resulted in reductions in HbA1c in all cohorts, which was generally maintained throughout the follow-up period. Average HbA1c reductions from the 6 months pre- to 1 year post-index date were -1.2% for GLP-1 RA, -1.6% for OADs, and -1.8% for basal insulin. HbA1c < 7.0% at 1 year occurred in 32.6%, 47.5%, and 41.1% of patients, respectively. Annual healthcare costs (mean [SD]) were lowest for OAD (US$10,074 [$22,276]) followed by GLP-1 RA (US$14,052 [$23,829]) and basal insulin (US$18,813 [$37,332]). Despite robust HbA1c lowering following treatment initiation, many patients did not achieve HbA1c < 7.0%. Basal insulin, generally prescribed for patients with high baseline HbA1c, was associated with a large reduction in HbA1c and with higher costs. Therapy intensification at an appropriate time could lead to clinical and economic benefits and should be investigated further. Sanofi U.S., Inc.

Switching to insulin glargine 300 U/mL: is duration of prior basal insulin therapy important?

PubMed

Bonadonna, Riccardo C; Renard, Eric; Cheng, Alice; Fritsche, Andreas; Cali, Anna; Melas-Melt, Lydie; Umpierrez, Guillermo E

2018-04-09

To assess the impact of duration of prior basal insulin therapy on study outcomes in people with type 2 diabetes mellitus receiving insulin glargine 300 U/mL (Gla-300) or insulin glargine 100 U/mL (Gla-100) for 6 months. A post hoc patient-level meta-analysis of data from the EDITION 1 and 2 studies. Outcomes included: HbA 1c , percentage of participants with ≥1 confirmed or severe hypoglycaemic event at night (00:00-05:59 h) or any time (24 h), and body weight change. Data were analysed according to duration of prior basal insulin use: >0-≤2 years, >2-≤5 years, >5 years. This meta-analysis included 1618 participants. HbA 1c change from baseline to month 6 was comparable between Gla-300 and Gla-100 groups, regardless of duration of prior basal insulin therapy. The lower risk with Gla-300 versus Gla-100 of ≥1 confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemic event, at night or any time (24 h), was unaffected by duration of prior basal insulin therapy. Similarly, weight change was unaffected by duration of prior basal insulin therapy. Switching to Gla-300 from other basal insulin therapies provided comparable glycaemic control with lower risk of hypoglycaemia versus Gla-100, regardless of duration of prior basal insulin therapy. Copyright © 2018. Published by Elsevier B.V.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hendrick, G.K.; Frizzell, R.T.; Cherrington, A.D.

In the 7-days fasted conscious dog, unlike the postabsorptive conscious dog, somatostatin infusion results in decreased levels of nonesterified fatty acids (NEFA) and increased glucose utilization (R{sub d}) even when insulin and glucagon levels are held constant. The aim of this study was to determine whether NEFA replacement in such animals would prevent the increase in R{sub d}. In each of three protocols there was an 80-min tracer equilibration period, a 40-min basal period, and a 3-h test period. During the test period in the first protocol saline was infused, in the second protocol somatostatin was infused along with intraportalmore » replacement amounts of insulin and glucagon (hormone replacement), while in the third protocol somatostatin plus the pancreatic hormones were infused with concurrent heparin plus Intralipid infusion. Glucose turnover was assessed using (3-{sup 3}H)glucose. The peripheral levels of insulin, glucagon, and glucose were similar and constant in all three protocols; however, during somatostatin infusion, exogenous glucose infusion was necessary to maintain euglycemia. The NEFA level was constant during saline infusion and decreased in the hormone replacement protocol. In the hormone replacement plus NEFA protocol, the NEFA level did not change during the first 90-min period and then increased during the second 90-min period. After a prolonged fast in the dog, (1) somatostatin directly or indirectly inhibits adipose tissue NEFA release and causes a decrease in the plasma NEFA level, and (2) this decrease in the NEFA level causes an increase in R{sub d}.« less

[Vesicular and nonvesicular glutamate release in the nucleus accumbens during a forced switch in behavioral strategy].

PubMed

Saul'skaia, N B; Mikhaĭlova, M O

2004-01-01

By means of in vivo microdialysis combined with HPLC analysis, we have shown that glutamate extracellular level in the rat n. accumbens increases during a forced switch in behavioral strategy. When infused in the n. accumbens, a Na+ channel blocker tetrodotoxin (TTX, 1 microM) completely prevents this increase whereas a potent cystine/glutamate exchanger blocker (S)-4-carboxyphenylglycine ((S)-4-CPG, 5 microM) has no effect. In contrast, TT (1 microM), infused in the n. accumbens, fails to significantly alter basal level of extracellular glutamate in this region whereas (S)-4-CPG (5 microM) produced a significant decrease. Our data suggest that basal and factional glutamate releases in the n. accumbens are differently regulated. The source of basal glutamate release is a non-vesicular release via cystine/glutamate exchanger. Functional glutamate release observed during a forced switch in behavioral strategy derives from vesicular synaptic pool.

Modulation of phosphoinositide turnover by chronic nicergoline in rat brain.

PubMed

Carfagna, N; Cavanus, S; Damiani, D; Salmoiraghi, P; Fariello, R; Post, C

1996-05-17

Basal and agonist-stimulated phosphoinositide (PI) turnover and inositol 1,4,5 -trisphospate (InsP3) content in rat brain were investigated after chronic nicergoline (SERMION) treatment. Oral administration of nicergoline (5 mg/kg b.i.d. for 7 weeks) enhanced the basal turnover of PI in the cerebral cortex compared to controls. This effect was paralleled by a significant rise of cortical InsP3 levels. No significant changes of noradrenaline- or carbachol-induced accumulation of [3H]-inositol-I-phophate ([3H]-InsP1) were found in cortices from nicergoline-treated rats. On the contrary, in the striatum nicergoline significantly potentiated the responsiveness of noradrenaline- and carbachol-stimulated PI turnover, leaving unchanged the basal production of [3H]-InsP1 and InsP3 levels. The results suggest that the interaction of nicergoline with PI transducing pathway might have relevance to the mechanisms of action of nicergoline.

Racial differences in tumor necrosis factor-α-induced endothelial microparticles and interleukin-6 production

PubMed Central

Brown, Michael D; Feairheller, Deborah L; Thakkar, Sunny; Veerabhadrappa, Praveen; Park, Joon-Young

2011-01-01

African Americans (AA) tend to have heightened systemic inflammation and endothelial dysfunction. Endothelial microparticles (EMP) are released from activated/apoptotic endothelial cells (EC) when stimulated by inflammation. The purpose of our study was to assess EMP responses to inflammatory cytokine (TNF-α) and antioxidant (superoxide dismutase, SOD) conditions in human umbilical vein ECs (HUVECs) obtained from AA and Caucasians. EMPs were measured under four conditions: control (basal), TNF-α, SOD, and TNF-α + SOD. Culture supernatant was collected for EMP analysis by flow cytometry and IL-6 assay by ELISA. IL-6 protein expression was assessed by Western blot. AA HUVECs had greater EMP levels under the TNF-α condition compared to the Caucasian HUVECs (6.8 ± 1.1 vs 4.7% ± 0.4%, P = 0.04). The EMP level increased by 89% from basal levels in the AA HUVECs under the TNF-α condition (P = 0.01) compared to an 8% increase in the Caucasian HUVECs (P = 0.70). Compared to the EMP level under the TNF-α condition, the EMP level in the AA HUVECs was lower under the SOD only condition (2.9% ± 0.3%, P = 0.005) and under the TNF-α + SOD condition (2.1% ± 0.4%, P = 0.001). Basal IL-6 concentrations were 56.1 ± 8.8 pg/mL/μg in the AA and 30.9 ± 14.9 pg/mL/μg in the Caucasian HUVECs (P = 0.17), while basal IL-6 protein expression was significantly greater (P < 0.05) in the AA HUVECs. These preliminary observational results suggest that AA HUVECs may be more susceptible to the injurious effects of the proinflammatory cytokine, TNF-α. PMID:21966220

Testing ecological and universal models of body shape and child health using a global sample of infants and young children.

PubMed

Hadley, Craig; Hruschka, Daniel J

2017-11-01

To test whether a risk of child illness is best predicted by deviations from a population-specific growth distribution or a universal growth distribution. Child weight for height and child illness data from 433 776 children (1-59 months) from 47 different low and lower income countries are used in regression models to estimate for each country the child basal weight for height. This study assesses the extent to which individuals within populations deviate from their basal slenderness. It uses correlation and regression techniques to estimate the relationship between child illness (diarrhoea, fever or cough) and basal weight for height, and residual weight for height. In bivariate tests, basal weight for height z-score did not predict the country level prevalence of child illness (r 2  = -0.01, n = 47, p = 0.53), but excess weight for height did (r 2  = 0.14, p < 0.01). At the individual level, household wealth is negatively associated with the odds that a child is reported as ill (beta = -0.04, p < 0.001, n = 433 776) and basal weight for height was not (beta = 0.20, p = 0.27). Deviations from country-specific basal weight for height were negatively associated with the likelihood of illness (beta = -0.13, p < 0.01), indicating a 13% reduction in illness risk for every 0.1 standard deviation increase in residual weight-for-height Conclusion: These results are consistent with the idea that populations may differ in their body slenderness, and that deviations from this body form may predict the risk of childhood illness.

COX-1 vs. COX-2 as a determinant of basal tone in the internal anal sphincter

PubMed Central

de Godoy, Márcio A. F.; Rattan, Neeru; Rattan, Satish

2009-01-01

Prostanoids, produced endogenously via cyclooxygenases (COXs), have been implicated in the sustained contraction of different smooth muscles. The two major types of COXs are COX-1 and COX-2. The COX subtype involved in the basal state of the internal anal sphincter (IAS) smooth muscle tone is not known. To identify the COX subtype, we examined the effect of COX-1- and COX-2-selective inhibitors, SC-560 and rofecoxib, respectively, on basal tone in the rat IAS. We also determined the effect of selective deletion of COX-1 and COX-2 genes (COX-1−/− and COX-2−/− mice) on basal tone in murine IAS. Our data show that SC-560 causes significantly more efficacious and potent concentration-dependent decreases in IAS tone than rofecoxib. In support of these data, significantly higher levels of COX-1 than COX-2 mRNA were found in the IAS. In addition, higher levels of COX-1 mRNA and protein were expressed in rat IAS than rectal smooth muscle. In wild-type mice, IAS tone was decreased 41.4 ± 3.4% (mean ± SE) by SC-560 (1 × 10−5 M) and 5.4 ± 2.2% by rofecoxib (P < 0.05, n = 5). Basal tone was 0.172 ± 0.021 mN//mg in the IAS from wild-type mice and significantly less (0.080 ± 0.015 mN/mg) in the IAS from COX-1−/− mice (P < 0.05, n = 5). However, basal tone in COX-2−/− mice was not significantly different from that in wild-type mice. We conclude that COX-1-related products contribute significantly to IAS tone. PMID:19056763

COX-1 vs. COX-2 as a determinant of basal tone in the internal anal sphincter.

PubMed

de Godoy, Márcio A F; Rattan, Neeru; Rattan, Satish

2009-02-01

Prostanoids, produced endogenously via cyclooxygenases (COXs), have been implicated in the sustained contraction of different smooth muscles. The two major types of COXs are COX-1 and COX-2. The COX subtype involved in the basal state of the internal anal sphincter (IAS) smooth muscle tone is not known. To identify the COX subtype, we examined the effect of COX-1- and COX-2-selective inhibitors, SC-560 and rofecoxib, respectively, on basal tone in the rat IAS. We also determined the effect of selective deletion of COX-1 and COX-2 genes (COX-1(-/-) and COX-2(-/-) mice) on basal tone in murine IAS. Our data show that SC-560 causes significantly more efficacious and potent concentration-dependent decreases in IAS tone than rofecoxib. In support of these data, significantly higher levels of COX-1 than COX-2 mRNA were found in the IAS. In addition, higher levels of COX-1 mRNA and protein were expressed in rat IAS than rectal smooth muscle. In wild-type mice, IAS tone was decreased 41.4 +/- 3.4% (mean +/- SE) by SC-560 (1 x 10(-5) M) and 5.4 +/- 2.2% by rofecoxib (P < 0.05, n = 5). Basal tone was 0.172 +/- 0.021 mN//mg in the IAS from wild-type mice and significantly less (0.080 +/- 0.015 mN/mg) in the IAS from COX-1(-/-) mice (P < 0.05, n = 5). However, basal tone in COX-2(-/-) mice was not significantly different from that in wild-type mice. We conclude that COX-1-related products contribute significantly to IAS tone.

Effects of Pine and Hardwood Basal Areas After Uneven-Aged Silvicultural Treatments on Wildlife Habitat

Treesearch

Darren A. Miller; Bruce D. Leopold; L. Mike Conner; Michael G. Shelton

1999-01-01

Uneven-aged management (UEAM) is becoming increasingly popular in the southeastern United States. However, effects of UEAM on wildlife habitat have not been adequately documented. We examined response of habitat within stands of varying levels of pine and hardwood basal area under an uneven-aged managegement regime in southern Mississippi. Summer and winter trends in...

Estimation of crown cover in interior ponderosa pine stands: Effects of thinning and prescribed fire

Treesearch

Nicholas Vaughn; Martin W. Ritchie

2005-01-01

We evaluated the relationship between crown cover measured with a vertical sight tube and stand basal area per acre in treated (thinned, burned, and thinned and burned) and untreated interior ponderosa pine (Pinus ponderosa P. & C. Lawson) stands in northeastern California. Crown cover was significantly related to basal area at the plot level and...

Heavy thinning of ponderosa pine stands: An Arizona case study

Treesearch

Peter F. Ffolliott; Jr. Baker; Gerald J. Gottfried

2000-01-01

Growth and structural changes in a mosaic of even-aged ponderosa pine (Pinus ponderosa) stands were studied for 25 years to determine the long-term impacts of a heavy thinning treatment to a basal-area level of 25 ft2/acre. Basal area and volume growth of these stands has increased since thinning and likely will continue to...

Growth of ponderosa pine thinned to different stocking levels in central Oregon: 30-year results.

Treesearch

P.H. Cochran; James W. Barrett

1999-01-01

Periodic annual increments (PAI) for survivor diameters decreased curvilinearly with increasing stand density. Gross volume and basal areas PAIs increased linearly with increasing stand density. Growth of basal area and volume for the 20 largest trees per acre were reduced curvilinearly with increasing stand density. Bark beetles were the primary cause of mortality. No...

Children's Comprehension of, Reactions to, and Preferences for Basal Reader Stories of Varying Comprehensibility. Technical Report No. 378.

ERIC Educational Resources Information Center

Meyer, Linda A.; And Others

A study examined children's comprehension of and preferences for basal reader stories with differing levels of coherence. The subjects were 58 second grade students who each read orally three stories judged to differ substantially on the number of incoherences in the text. Incoherences were defined as confusing referents, unclear relationships…

Enhancement of hippocampal mossy fiber activity in zinc deficiency and its influence on behavior.

PubMed

Takeda, Atsushi; Itoh, Hiromasa; Yamada, Kohei; Tamano, Haruna; Oku, Naoto

2008-10-01

The extracellular concentration of glutamate in the hippocampus is increased by hippocampal perfusion with CaEDTA, a membrane-impermeable zinc chelator, suggesting that the activity of glutamatergic neurons in the hippocampus are influenced by the extracellular concentrations of zinc. In the present study, the relationship between the extracellular concentrations of zinc and mossy fiber activity in the hippocampus was examined in mice and rats fed a zinc-deficient diet for 4 weeks. Timm's stain, by which histochemically reactive zinc in the presynaptic vesicles is detected, was attenuated in the hippocampus in zinc deficiency. The extracellular signal of ZnAF-2, a membrane-impermeable zinc indicator, was also lower in the hippocampal CA3, suggesting that the basal extracellular concentrations of zinc are lower maintained in zinc deficiency. To check mossy fiber activity after 4-week zinc deprivation, the decrease in the signal of FM4-64, an indicator of presynaptic activity (exocytosis), at mossy fiber synapses was measured under the condition of spontaneous depolarization. The decrease was significantly facilitated by zinc deficiency, suggesting that the basal exocytosis at mossy fiber synapses is enhanced by zinc deficiency. On the other hand, the increase in anxiety-like behavior was observed in the open-field test after 4-week zinc deprivation. The present study demonstrates that the decrease in the basal extracellular concentrations of zinc may be linked to the enhancement of the basal mossy fiber activity in zinc deficiency. This decrease seems to be also involved in neuropsychological behavior in zinc deficiency.

Mammary collective cell migration involves transient loss of epithelial features and individual cell migration within the epithelium

PubMed Central

Ewald, Andrew J.; Huebner, Robert J.; Palsdottir, Hildur; Lee, Jessie K.; Perez, Melissa J.; Jorgens, Danielle M.; Tauscher, Andrew N.; Cheung, Kevin J.; Werb, Zena; Auer, Manfred

2012-01-01

Normal mammary morphogenesis involves transitions between simple and multilayered epithelial organizations. We used electron microscopy and molecular markers to determine whether intercellular junctions and apico-basal polarity were maintained in the multilayered epithelium. We found that multilayered elongating ducts had polarized apical and basal tissue surfaces both in three-dimensional culture and in vivo. However, individual cells were only polarized on surfaces in contact with the lumen or extracellular matrix. The basolateral marker scribble and the apical marker atypical protein kinase C zeta localized to all interior cell membranes, whereas PAR3 displayed a cytoplasmic localization, suggesting that the apico-basal polarity was incomplete. Despite membrane localization of E-cadherin and β-catenin, we did not observe a defined zonula adherens connecting interior cells. Instead, interior cells were connected through desmosomes and exhibited complex interdigitating membrane protrusions. Single-cell labeling revealed that individual cells were both protrusive and migratory within the epithelial multilayer. Inhibition of Rho kinase (ROCK) further reduced intercellular adhesion on apical and lateral surfaces but did not disrupt basal tissue organization. Following morphogenesis, segregated membrane domains were re-established and junctional complexes re-formed. We observed similar epithelial organization during mammary morphogenesis in organotypic culture and in vivo. We conclude that mammary epithelial morphogenesis involves a reversible, spatially limited, reduction in polarity and intercellular junctions and active individualistic cell migration. Our data suggest that reductions in polarity and adhesion during breast cancer progression might reflect partial recapitulation of a normal developmental program. PMID:22344263

Evolutionarily conserved mechanisms for the selection and maintenance of behavioural activity.

PubMed

Fiore, Vincenzo G; Dolan, Raymond J; Strausfeld, Nicholas J; Hirth, Frank

2015-12-19

Survival and reproduction entail the selection of adaptive behavioural repertoires. This selection manifests as phylogenetically acquired activities that depend on evolved nervous system circuitries. Lorenz and Tinbergen already postulated that heritable behaviours and their reliable performance are specified by genetically determined programs. Here we compare the functional anatomy of the insect central complex and vertebrate basal ganglia to illustrate their role in mediating selection and maintenance of adaptive behaviours. Comparative analyses reveal that central complex and basal ganglia circuitries share comparable lineage relationships within clusters of functionally integrated neurons. These clusters are specified by genetic mechanisms that link birth time and order to their neuronal identities and functions. Their subsequent connections and associated functions are characterized by similar mechanisms that implement dimensionality reduction and transition through attractor states, whereby spatially organized parallel-projecting loops integrate and convey sensorimotor representations that select and maintain behavioural activity. In both taxa, these neural systems are modulated by dopamine signalling that also mediates memory-like processes. The multiplicity of similarities between central complex and basal ganglia suggests evolutionarily conserved computational mechanisms for action selection. We speculate that these may have originated from ancestral ground pattern circuitries present in the brain of the last common ancestor of insects and vertebrates. © 2015 The Authors.

Evolutionarily conserved mechanisms for the selection and maintenance of behavioural activity

PubMed Central

Fiore, Vincenzo G.; Dolan, Raymond J.; Strausfeld, Nicholas J.; Hirth, Frank

2015-01-01

Survival and reproduction entail the selection of adaptive behavioural repertoires. This selection manifests as phylogenetically acquired activities that depend on evolved nervous system circuitries. Lorenz and Tinbergen already postulated that heritable behaviours and their reliable performance are specified by genetically determined programs. Here we compare the functional anatomy of the insect central complex and vertebrate basal ganglia to illustrate their role in mediating selection and maintenance of adaptive behaviours. Comparative analyses reveal that central complex and basal ganglia circuitries share comparable lineage relationships within clusters of functionally integrated neurons. These clusters are specified by genetic mechanisms that link birth time and order to their neuronal identities and functions. Their subsequent connections and associated functions are characterized by similar mechanisms that implement dimensionality reduction and transition through attractor states, whereby spatially organized parallel-projecting loops integrate and convey sensorimotor representations that select and maintain behavioural activity. In both taxa, these neural systems are modulated by dopamine signalling that also mediates memory-like processes. The multiplicity of similarities between central complex and basal ganglia suggests evolutionarily conserved computational mechanisms for action selection. We speculate that these may have originated from ancestral ground pattern circuitries present in the brain of the last common ancestor of insects and vertebrates. PMID:26554043

Neurotensin receptor binding levels in basal ganglia are not altered in Huntington's chorea or schizophrenia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palacios, J.M.; Chinaglia, G.; Rigo, M.

1991-02-01

Autoradiographic techniques were used to examine the distribution and levels of neurotensin receptor binding sites in the basal ganglia and related regions of the human brain. Monoiodo ({sup 125}I-Tyr3)neurotensin was used as a ligand. High amounts of neurotensin receptor binding sites were found in the substantia nigra pars compacta. Lower but significant quantities of neurotensin receptor binding sites characterized the caudate, putamen, and nucleus accumbens, while very low quantities were seen in both medial and lateral segments of the globus pallidus. In Huntington's chorea, the levels of neurotensin receptor binding sites were found to be comparable to those of controlmore » cases. Only slight but not statistically significant decreases in amounts of receptor binding sites were detected in the dorsal part of the head and in the body of caudate nucleus. No alterations in the levels of neurotensin receptor binding sites were observed in the substantia nigra pars compacta and reticulata. These results suggest that a large proportion of neurotensin receptor binding sites in the basal ganglia are located on intrinsic neurons and on extrinsic afferent fibers that do not degenerate in Huntington's disease.« less

Systemic Injections of Cannabidiol Enhance Acetylcholine Levels from Basal Forebrain in Rats.

PubMed

Murillo-Rodríguez, Eric; Arankowsky-Sandoval, Gloria; Rocha, Nuno Barbosa; Peniche-Amante, Rodrigo; Veras, André Barciela; Machado, Sérgio; Budde, Henning

2018-06-06

Cannabis sativa is a plant that contains more than 500 components, of which the most studied are Δ 9 -tetrahydrocannabinol (Δ 9 -THC) and cannabidiol (CBD). Several studies have indicated that CBD displays neurobiological effects, including wake promotion. Moreover, experimental evidence has shown that injections of CBD enhance wake-related compounds, such as monoamines (dopamine, serotonin, epinephrine, and norepinephrine). However, no clear evidence is available regarding the effects of CBD on additional wake-related neurochemicals such as acetylcholine (ACh). Here, we demonstrate that systemic injections of CBD (0, 5, 10 or 30 mg/kg, i.p.) at the beginning of the lights-on period, increase the extracellular levels of ACh collected from the basal forebrain and measured by microdialysis and HPLC means. Moreover, the time course effects on the contents of ACh were present 5 h post-injection of CBD. Altogether, these data demonstrate that CBD increases ACh levels in a brain region related to wake control. This study is the first to show the effects of ACh levels in CBD-treated rats and suggests that the basal forebrain might be a site of action of CBD for wakefulness modulation.

[The changes in renin-angiotensin-aldosterone-system in different subtypes of Cushing's syndrome].

PubMed

Cui, Jia; Dou, Jingtao; Yang, Guoqing; Zang, Li; Jin, Nan; Chen, Kang; Du, Jin; Gu, Weijun; Wang, Xianling; Yang, Lijuan; Lyu, Zhaohui; Ba, Jianming; Mu, Yiming; Lu, Juming; Li, Jiangyuan; Pan, Changyu

2015-07-01

Cushing's syndrome is a clinical condition resulting from chronic exposure to excess glucocorticoid. As a consequence, long-term hypercortisolism contributes significantly to the development of systemic disorders by direct and/or indirect effects. The present study was to analyze the changes of renin-angiotensin-aldosterone-system in different subtypes of Cushing's syndrome on the standard posture test. We retrospectively reviewed 150 patients with histologically confirmed Cushing's syndrome treated at the PLA General Hospital between 2002 and 2014. Among them, 128 patients were diagnosed as adreno-cortico-tropic-hormone (ACTH)-independent Cushing's syndrome, and 22 were ACTH-dependent Cushing's syndrome. All patients were undertaken the posture test. Plasma renin activity (PRA), angiotensin II, plasma aldosterone concertration (PAC) levels were measured before and after the test. Basal plasma PRA [0.5 (0.2,1.3)µg·L(-1)·h(-1), angiotensin II [(48.9±20.1) ng/L] and PAC [(285.0±128.1) pmol/L] levels were within the normal range in supine position. Compared with the subjects with ACTH-independent Cushing's syndrome, the basal PAC levels were higher in subjects with ACTH-dependent Cushing's syndrome [(348.0±130.4) pmol/L vs (274.2±125.0) pmol/L, P<0.05]. However, the PAC response in subjects with ACTH-dependent Cushing's syndrome [(49.7±26.4)%] was significantly lower than that in those with ACTH-independent Cushing's syndrome [(81.2±69.3)%] upon upright posture stimulation (P<0.05). There were no statistical significances in PRA and angiotensin II levels between the two groups. The basal PAC and PRA levels were positively correlated with ACTH, whereas PAC response was negatively correlated with ACTH. The renin-angiotensin-aldosterone-system activity in subjects with Cushing's syndrome was similar to that in normal control. The basal PAC level and its response to upright posture are differently associated with ACTH level in Cushing's syndrome.

Light-Induced Alterations in Basil Ganglia Kynurenic Acid Levels

NASA Technical Reports Server (NTRS)

Sroufe, Angela E.; Whittaker, J. A.; Patrickson, J. W.; Orr, M. C.

1997-01-01

The metabolic synthesis, release and breakdown of several known CNS neurotransmitters have been shown to follow a circadian pattern entrained to the environmental light/dark cycle. The levels of excitatory amino acid (EAA) transmitters such as glutamate, have been shown to vary with environmental lighting conditions. Kynurenic Acid (KA), an endogenous tryptophan metabolite and glutamate receptor antagonist, has been reported to have neuroprotective effects against EAA-induced excitotoxic cell damage. Changes in KA's activity within the mammalian basal ganglia has been proposed as being contributory to neurotoxicity in Huntington's Disease. It is not known whether CNS KA levels follow a circadian pattern or exhibit light-induced fluctuations. However, because the symptoms of certain degenerative motor disorders seem to fluctuate with daily 24 hour rhythm, we initiated studies to determine if basal ganglia KA were influenced by the daily light/dark cycle and could influence motor function. Therefore in this study, HPLC-EC was utilized to determine if basal ganglia KA levels in tissue extracts from adult male Long-Evans rats (200-250g) entrained to 24 and 48 hours constant light and dark conditions, respectively. Samples were taken one hour before the onset of the subjective day and one hour prior to the onset of the subjective night in order to detect possible phase differences in KA levels and to allow for accumulation of factors expressed in association with the light or dark phase. Data analysis revealed that KA levels in the basal ganglia vary with environmental lighting conditions; being elevated generally during the dark. Circadian phase differences in KA levels were also evident during the subjective night and subjective day, respectively. Results from these studies are discussed with respect to potential cyclic changes in neuronal susceptibility to excitotoxic damage during the daily 24 hour cycle and its possible relevance to future therapeutic approaches in treating neurodegenerative disorders.

Left-to-right atrial inward rectifier potassium current gradients in patients with paroxysmal versus chronic atrial fibrillation.

PubMed

Voigt, Niels; Trausch, Anne; Knaut, Michael; Matschke, Klaus; Varró, András; Van Wagoner, David R; Nattel, Stanley; Ravens, Ursula; Dobrev, Dobromir

2010-10-01

Recent evidence suggests that atrial fibrillation (AF) is maintained by high-frequency reentrant sources with a left-to-right-dominant frequency gradient, particularly in patients with paroxysmal AF (pAF). Unequal left-to-right distribution of inward rectifier K(+) currents has been suggested to underlie this dominant frequency gradient, but this hypothesis has never been tested in humans. Currents were measured with whole-cell voltage-clamp in cardiomyocytes from right atrial (RA) and left (LA) atrial appendages of patients in sinus rhythm (SR) and patients with AF undergoing cardiac surgery. Western blot was used to quantify protein expression of I(K1) (Kir2.1 and Kir2.3) and I(K,ACh) (Kir3.1 and Kir3.4) subunits. Basal current was ≈2-fold larger in chronic AF (cAF) versus SR patients, without RA-LA differences. In pAF, basal current was ≈2-fold larger in LA versus RA, indicating a left-to-right atrial gradient. In both atria, Kir2.1 expression was ≈2-fold greater in cAF but comparable in pAF versus SR. Kir2.3 levels were unchanged in cAF and RA-pAF but showed a 51% decrease in LA-pAF. In SR, carbachol-activated (2 μmol/L) I(K,ACh) was 70% larger in RA versus LA. This right-to-left atrial gradient was decreased in pAF and cAF caused by reduced I(K,ACh) in RA only. Similarly, in SR, Kir3.1 and Kir3.4 proteins were greater in RA versus LA and decreased in RA of pAF and cAF. Kir3.1 and Kir3.4 expression was unchanged in LA of pAF and cAF. Our results support the hypothesis that a left-to-right gradient in inward rectifier background current contributes to high-frequency sources in LA that maintain pAF. These findings have potentially important implications for development of atrial-selective therapeutic approaches.

Left-to-Right Atrial Inward Rectifier Potassium Current Gradients in Patients With Paroxysmal Versus Chronic Atrial Fibrillation

PubMed Central

Voigt, Niels; Trausch, Anne; Knaut, Michael; Matschke, Klaus; Varró, András; Van Wagoner, David R.; Nattel, Stanley; Ravens, Ursula; Dobrev, Dobromir

2018-01-01

Background Recent evidence suggests that atrial fibrillation (AF) is maintained by high-frequency reentrant sources with a left-to-right–dominant frequency gradient, particularly in patients with paroxysmal AF (pAF). Unequal left-to-right distribution of inward rectifier K+ currents has been suggested to underlie this dominant frequency gradient, but this hypothesis has never been tested in humans. Methods and Results Currents were measured with whole-cell voltage-clamp in cardiomyocytes from right atrial (RA) and left (LA) atrial appendages of patients in sinus rhythm (SR) and patients with AF undergoing cardiac surgery. Western blot was used to quantify protein expression of IK1 (Kir2.1 and Kir2.3) and IK,ACh (Kir3.1 and Kir3.4) subunits. Basal current was ≈2-fold larger in chronic AF (cAF) versus SR patients, without RA-LA differences. In pAF, basal current was ≈2-fold larger in LA versus RA, indicating a left-to-right atrial gradient. In both atria, Kir2.1 expression was ≈2-fold greater in cAF but comparable in pAF versus SR. Kir2.3 levels were unchanged in cAF and RA-pAF but showed a 51% decrease in LA-pAF. In SR, carbachol-activated (2 μmol/L) IK,ACh was 70% larger in RA versus LA. This right-to-left atrial gradient was decreased in pAF and cAF caused by reduced IK,ACh in RA only. Similarly, in SR, Kir3.1 and Kir3.4 proteins were greater in RA versus LA and decreased in RA of pAF and cAF. Kir3.1 and Kir3.4 expression was unchanged in LA of pAF and cAF. Conclusions Our results support the hypothesis that a left-to-right gradient in inward rectifier background current contributes to high-frequency sources in LA that maintain pAF. These findings have potentially important implications for development of atrial-selective therapeutic approaches. PMID:20657029

Here, there be dragons: charting autophagy-related alterations in human tumors.

PubMed

Lebovitz, Chandra B; Bortnik, Svetlana B; Gorski, Sharon M

2012-03-01

Macroautophagy (or autophagy) is a catabolic cellular process that is both homeostatic and stress adaptive. Normal cells rely on basal levels of autophagy to maintain cellular integrity (via turnover of long-lived proteins and damaged organelles) and increased levels of autophagy to buoy cell survival during various metabolic stresses (via nutrient and energy provision through lysosomal degradation of cytoplasmic components). Autophagy can function in both tumor suppression and tumor progression, and is under investigation in clinical trials as a novel target for anticancer therapy. However, its role in cancer pathogenesis has yet to be fully explored. In particular, it remains unknown whether in vitro observations will be applicable to human cancer patients. Another outstanding question is whether there exists tumor-specific selection for alterations in autophagy function. In this review, we survey reported mutations in autophagy genes and key autophagy regulators identified in human tumor samples and summarize the literature regarding expression levels of autophagy genes and proteins in various cancer tissues. Although it is too early to draw inferences from this collection of in vivo studies of autophagy-related alterations in human cancers, their results highlight the challenges that must be overcome before we can accurately assess the scope of autophagy's predicted role in tumorigenesis.

Intensity coding in electric hearing: Effects of electrode configurations and stimulation waveforms

PubMed Central

Chua, Tiffany Elise H.; Bachman, Mark; Zeng, Fan-Gang

2011-01-01

Objectives Current cochlear implants typically stimulate the auditory nerve with biphasic pulses and monopolar electrode configurations. Tripolar stimulation can increase spatial selectivity and potentially improve place pitch related perception, but requires higher current levels to elicit the same loudness as monopolar stimulation. The present study combined delayed pseudomonophonasic pulses, which produce lower thresholds, with tripolar stimulation in an attempt to solve the power-performance tradeoff problem. Design The present study systematically measured thresholds, dynamic range, loudness growth, and intensity discrimination using either biphasic or delayed pseudomonophonasic pulses under both monopolar and tripolar stimulation. Participants were 5 Clarion cochlear implant users. For each subject, data from apical, middle and basal electrode positions were collected when possible. Results Compared with biphasic pulses, delayed pseudomonophonasic pulses increased the dynamic range by lowering thresholds while maintaining comparable maximum allowable levels under both electrode configurations. However, delayed pseudomonophonasic pulses did not change the shape of loudness growth function and actually increased intensity discrimination limens, especially at lower current levels. Conclusions The present results indicate that delayed pseudomonophonasic pulses coupled with tripolar stimulation cannot provide significant power savings, nor can it increase the functional dynamic range. Whether this combined stimulation could improve functional spectral resolution remains to be seen. PMID:21610498

Noise level in a pediatric intensive care unit.

PubMed

Carvalho, Werther B; Pedreira, Mavilde L G; de Aguiar, Maria Augusta L

2005-01-01

The purpose of this study was to verify the noise level at a PICU. This prospective observational study was performed in a 10 bed PICU at a teaching hospital located in a densely populated district within the city of São Paulo, Brazil. Sound pressure levels (dBA) were measured 24 hours during a 6-day period. Noise recording equipment was placed in the PICU access corridor, nursing station, two open wards with three and five beds, and in isolation rooms. The resulting curves were analyzed. A basal noise level variation between 60 and 70 dBA was identified, with a maximum level of 120 dBA. The most significant noise levels were recorded during the day and were produced by the staff. The basal noise level identified exceeds International Noise Council recommendations. Education regarding the effects of noise on human hearing and its relation to stress is the essential basis for the development of a noise reduction program.

Selective Activation of Basal Forebrain Cholinergic Neurons Attenuates Polymicrobial Sepsis-Induced Inflammation via the Cholinergic Anti-Inflammatory Pathway.

PubMed

Zhai, Qian; Lai, Dengming; Cui, Ping; Zhou, Rui; Chen, Qixing; Hou, Jinchao; Su, Yunting; Pan, Libiao; Ye, Hui; Zhao, Jing-Wei; Fang, Xiangming

2017-10-01

Basal forebrain cholinergic neurons are proposed as a major neuromodulatory system in inflammatory modulation. However, the function of basal forebrain cholinergic neurons in sepsis is unknown, and the neural pathways underlying cholinergic anti-inflammation remain unexplored. Animal research. University research laboratory. Male wild-type C57BL/6 mice and ChAT-ChR2-EYFP (ChAT) transgenic mice. The cholinergic neuronal activity of the basal forebrain was manipulated optogenetically. Cecal ligation and puncture was produced to induce sepsis. Left cervical vagotomy and 6-hydroxydopamine injection to the spleen were used. Photostimulation of basal forebrain cholinergic neurons induced a significant decrease in the levels of tumor necrosis factor-α and interleukin-6 in the serum and spleen. When cecal ligation and puncture was combined with left cervical vagotomy in photostimulated ChAT mice, these reductions in tumor necrosis factor-α and interleukin-6 were partly reversed. Furthermore, photostimulating basal forebrain cholinergic neurons induced a large increase in c-Fos expression in the basal forebrain, the dorsal motor nucleus of the vagus, and the ventral part of the solitary nucleus. Among them, 35.2% were tyrosine hydroxylase positive neurons. Furthermore, chemical denervation showed that dopaminergic neurotransmission to the spleen is indispensable for the anti-inflammation. These results are the first to demonstrate that selectively activating basal forebrain cholinergic neurons is sufficient to attenuate systemic inflammation in sepsis. Specifically, photostimulation of basal forebrain cholinergic neurons activated dopaminergic neurons in dorsal motor nucleus of the vagus/ventral part of the solitary nucleus, and this dopaminergic efferent signal was further transmitted by the vagus nerve to the spleen. This cholinergic-to-dopaminergic neural circuitry, connecting central cholinergic neurons to the peripheral organ, might have mediated the anti-inflammatory effect in sepsis.

The evolutionary origin of the vertebrate basal ganglia and its role in action selection.

PubMed

Grillner, Sten; Robertson, Brita; Stephenson-Jones, Marcus

2013-11-15

The group of nuclei within the basal ganglia of the forebrain is central to the control of movement. We present data showing that the structure and function of the basal ganglia have been conserved throughout vertebrate evolution over some 560 million years. The interaction between the different nuclei within the basal ganglia is conserved as well as the cellular and synaptic properties and transmitters. We consider the role of the conserved basal ganglia circuitry for basic patterns of motor behaviour controlled via brainstem circuits. The output of the basal ganglia consists of tonically active GABAergic neurones, which target brainstem motor centres responsible for different patterns of behaviour, such as eye and locomotor movements, posture, and feeding. A prerequisite for activating or releasing a motor programme is that this GABAergic inhibition is temporarily reduced. This can be achieved through activation of GABAergic projection neurons from striatum, the input level of the basal ganglia, given an appropriate synaptic drive from cortex, thalamus and the dopamine system. The tonic inhibition of the motor centres at rest most likely serves to prevent the different motor programmes from becoming active when not intended. Striatal projection neurones are subdivided into one group with dopamine 1 receptors that provides increased excitability of the direct pathway that can initiate movements, while inhibitory dopamine 2 receptors are expressed on neurones that instead inhibit movements and are part of the 'indirect loop' in mammals as well as lamprey. We review the evidence showing that all basic features of the basal ganglia have been conserved throughout vertebrate phylogeny, and discuss these findings in relation to the role of the basal ganglia in selection of behaviour.

Sequential development of apical-basal and planar polarities in aggregating epitheliomuscular cells of Hydra.

PubMed

Seybold, Anna; Salvenmoser, Willi; Hobmayer, Bert

2016-04-01

Apical-basal and planar cell polarities are hallmarks of metazoan epithelia required to separate internal and external environments and to regulate trans- and intracellular transport, cytoskeletal organization, and morphogenesis. Mechanisms of cell polarization have been intensively studied in bilaterian model organisms, particularly in early embryos and cultured cells, while cell polarity in pre-bilaterian tissues is poorly understood. Here, we have studied apical-basal and planar polarization in regenerating (aggregating) clusters of epitheliomuscular cells of Hydra, a simple representative of the ancestral, pre-bilaterian phylum Cnidaria. Immediately after dissociation, single epitheliomuscular cells do not exhibit cellular polarity, but they polarize de novo during aggregation. Reestablishment of the Hydra-specific epithelial bilayer is a result of short-range cell sorting. In the early phase of aggregation, apical-basal polarization starts with an enlargement of the epithelial apical-basal diameter and by the development of belt-like apical septate junctions. Specification of the basal pole of epithelial cells occurs shortly later and is linked to synthesis of mesoglea, development of hemidesmosome-like junctions, and formation of desmosome-like junctions connecting the basal myonemes of neighbouring cells. Planar polarization starts, while apical-basal polarization is already ongoing. It is executed gradually starting with cell-autonomous formation, parallelization, and condensation of myonemes at the basal end of each epithelial cell and continuing with a final planar alignment of epitheliomuscular cells at the tissue level. Our findings reveal that epithelial polarization in Hydra aggregates occurs in defined steps well accessible by histological and ultrastructural techniques and they will provide a basis for future molecular studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Associations between basal cortisol levels and memory retrieval in healthy young individuals.

PubMed

Ackermann, Sandra; Hartmann, Francina; Papassotiropoulos, Andreas; de Quervain, Dominique J F; Rasch, Björn

2013-11-01

Cortisol is known to affect memory processes. On the one hand, stress-induced or pharmacologically induced elevations of cortisol levels enhance memory consolidation. On the other hand, such experimentally induced elevations of cortisol levels have been shown to impair memory retrieval. However, the effects of individual differences in basal cortisol levels on memory processes remain largely unknown. Here we tested whether individual differences in cortisol levels predict picture learning and recall in a large sample. A total of 1225 healthy young women and men viewed two different sets of emotional and neutral pictures on two consecutive days. Both sets were recalled after a short delay (10 min). On Day 2, the pictures seen on Day 1 were additionally recalled, resulting in a long-delay (20 hr) recall condition. Cortisol levels were measured three times on Days 1 and 2 via saliva samples before encoding, between encoding and recall as well as after recall testing. We show that stronger decreases in cortisol levels during retrieval testing were associated with better recall performance of pictures, regardless of emotional valence of the pictures or length of the retention interval (i.e., 10 min vs. 20 hr). In contrast, average cortisol levels during retrieval were not related to picture recall. Remarkably during encoding, individual differences in average cortisol levels as well as changes in cortisol did not predict memory recall. Our results support previous findings indicating that higher cortisol levels during retrieval testing hinders recall of episodic memories and extend this view onto interindividual changes in basal cortisol levels.

Betaine acts on a ligand-gated ion channel in the nervous system of the nematode C. elegans

PubMed Central

Peden, Aude S.; Mac, Patrick; Fei, You-Jun; Castro, Cecilia; Jiang, Guoliang; Murfitt, Kenneth J.; Miska, Eric A.; Griffin, Julian L.; Ganapathy, Vadivel; Jorgensen, Erik M.

2014-01-01

Prior to the advent of synthetic nematocides, natural products such as seaweed were used to control nematode infestations. The nematocidal agent in seaweed is betaine, an amino acid that functions as an osmolyte and methyl donor. However, the molecular mechanisms of betaine toxicity are unknown. Here, we identify the betaine transporter SNF-3 and a betaine receptor ACR-23 in the nematode C. elegans. Mutating snf-3 in a sensitized background causes the animals to be hypercontracted and paralyzed, presumably because of excess extracellular betaine. These behavioral defects are suppressed by mutations in acr-23, which encodes a ligand-gated cation channel of the cys-loop family. ACR-23 is activated by betaine and functions in the mechanosensory neurons to maintain basal levels of locomotion. However, overactivation of the receptor by excess betaine or by the allosteric modulator monepantel causes hypercontraction and death of the nematode. Thus, monepantel targets a betaine signaling pathway in nematodes. PMID:24212673

Protein Kinase A Subunit Balance Regulates Lipid Metabolism in Caenorhabditis elegans and Mammalian Adipocytes*

PubMed Central

Lee, Jung Hyun; Han, Ji Seul; Kong, Jinuk; Ji, Yul; Lv, Xuchao; Lee, Junho; Li, Peng; Kim, Jae Bum

2016-01-01

Protein kinase A (PKA) is a cyclic AMP (cAMP)-dependent protein kinase composed of catalytic and regulatory subunits and involved in various physiological phenomena, including lipid metabolism. Here we demonstrated that the stoichiometric balance between catalytic and regulatory subunits is crucial for maintaining basal PKA activity and lipid homeostasis. To uncover the potential roles of each PKA subunit, Caenorhabditis elegans was used to investigate the effects of PKA subunit deficiency. In worms, suppression of PKA via RNAi resulted in severe phenotypes, including shortened life span, decreased egg laying, reduced locomotion, and altered lipid distribution. Similarly, in mammalian adipocytes, suppression of PKA regulatory subunits RIα and RIIβ via siRNAs potently stimulated PKA activity, leading to potentiated lipolysis without increasing cAMP levels. Nevertheless, insulin exerted anti-lipolytic effects and restored lipid droplet integrity by antagonizing PKA action. Together, these data implicate the importance of subunit stoichiometry as another regulatory mechanism of PKA activity and lipid metabolism. PMID:27496951

Mollusc C-reactive protein crosses species barrier and reverses hepatotoxicity of lead in rodent models.

PubMed

Mukherjee, Sandip; Chatterjee, Sarmishtha; Sarkar, Shuvasree; Agarwal, Soumik; Kundu, Rakesh; Maitra, Sudipta; Bhattacharya, Shelley

2013-08-01

Achatina fulica C-reactive protein (ACRP) reversed the toxic effects of lead nitrate both in vivo in mice and in vitro in rat hepatocytes restoring the basal level of cell viability, lipid peroxidation, reduced glutathione and superoxides. Cytotoxicity was also significantly ameliorated in rat hepatocytes by in vitro pre-treatments with individual subunits (60, 62, 90 and 110 kDa) of ACRP. Annexin V-Cy3/CFDA dual staining showed significant reduction in the number of apoptotic hepatocytes pre-treated with ACRP. ACRP induced restoration of mitochondrial membrane potential was remarkable. ACRP pre-treatment prevented Pb-induced apoptosis mediated by caspase activation. The antagonistic effect of ACRP may be due to scavenging of reactive oxygen species which maintained the homeostasis of cellular redox potential as well as reduced glutathione status. The results suggest that ACRP crosses the species barrier and it may be utilized as a viable exogenous agent of cytoprotection against heavy metal related toxicity.

Comparative endocrinological responses to short transportation of Equidae (Equus asinus and Equus caballus).

PubMed

Fazio, Esterina; Medica, Pietro; Cravana, Cristina; Aveni, Francesca; Ferlazzo, Adriana

2013-03-01

In order to evaluate the effects of short transportation on β-endorphin, adrenocorticotropic hormone (ACTH) and cortisol changes, 12 healthy stallions of Equidae (Equus asinus and Equus caballus) were studied before and after transportation of 50 km. Blood samples were collected 1 week before transportation in basal conditions, immediately before loading and after transportation and unloading, on their arrival at the breeding station. Compared to basal and before values, donkeys showed an increase in circulating ACTH (P < 0.001) and cortisol (P < 0.0005) levels after transportation and higher ACTH (P < 0.01) levels than horses after transportation. A positive and significant correlation (r = 0.885; P < 0.01) between ACTH and cortisol levels after transportation was found. No significant differences were observed for β-endorphin levels. Compared to basal and before values, horses showed higher cortisol (P < 0.005) levels after transportation and no significant differences were observed for ACTH and β-endorphin levels in donkeys. Horses facing forward (direction of travel) showed higher (P < 0.01) β-endorphin levels after transportation than donkeys; horses facing backward (the opposite direction of travel) showed lower (P < 0.05) ACTH levels after transportation. The results indicate that short transportation induces a preferential activation of the hypothalamus-pituitary-axis (HPA), with significant release of ACTH and cortisol in donkeys and only of cortisol in horses, suggesting that transportation for donkeys may be more stressful than horses. © 2012 The Authors Animal Science Journal © 2012 Japanese Society of Animal Science.

PGE2 /EP4 Signaling Controls the Transfer of the Mammary Stem Cell State by Lipid Rafts in Extracellular Vesicles.

PubMed

Lin, Meng-Chieh; Chen, Shih-Yin; Tsai, Ho-Min; He, Pei-Lin; Lin, Yen-Chun; Herschman, Harvey; Li, Hua-Jung

2017-02-01

Prostaglandin E 2 (PGE 2 )-initiated signaling contributes to stem cell homeostasis and regeneration. However, it is unclear how PGE 2 signaling controls cell stemness. This study identifies a previously unknown mechanism by which PGE 2 /prostaglandin E receptor 4 (EP 4 ) signaling regulates multiple signaling pathways (e.g., PI3K/Akt signaling, TGFβ signaling, Wnt signaling, EGFR signaling) which maintain the basal mammary stem cell phenotype. A shift of basal mammary epithelial stem cells (MaSCs) from a mesenchymal/stem cell state to a non-basal-MaSC state occurs in response to prostaglandin E receptor 4 (EP 4 ) antagonism. EP 4 antagonists elicit release of signaling components, by controlling their trafficking into extracellular vesicles/exosomes in a lipid raft/caveolae-dependent manner. Consequently, EP 4 antagonism indirectly inactivates, through induced extracellular vesicle/exosome release, pathways required for mammary epithelial stem cell homeostasis, e.g. canonical/noncanonical Wnt, TGFβ and PI3K/Akt pathways. EP 4 antagonism causes signaling receptors and signaling components to shift from non-lipid raft fractions to lipid raft fractions, and to then be released in EP 4 antagonist-induced extracellular vesicles/exosomes, resulting in the loss of the stem cell state by mammary epithelial stem cells. In contrast, luminal mammary epithelial cells can acquire basal stem cell properties following ingestion of EP 4 antagonist-induced stem cell extracellular vesicles/exosomes, and can then form mammary glands. These findings demonstrate that PGE 2 /EP 4 signaling controls homeostasis of mammary epithelial stem cells through regulating extracellular vesicle/exosome release. Reprogramming of mammary epithelial cells can result from EP 4 -mediated stem cell property transfer by extracellular vesicles/exosomes containing caveolae-associated proteins, between mammary basal and luminal epithelial cells. Stem Cells 2017;35:425-444. © 2016 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Relationships between root diameter, root length and root branching along lateral roots in adult, field-grown maize

PubMed Central

Wu, Qian; Pagès, Loïc; Wu, Jie

2016-01-01

Background and Aims Root diameter, especially apical diameter, plays an important role in root development and function. The variation in diameter between roots, and along roots, affects root structure and thus the root system’s overall foraging performance. However, the effect of diameter variation on root elongation, branching and topological connections has not been examined systematically in a population of high-order roots, nor along the roots, especially for mature plants grown in the field. Methods A method combining both excavation and analysis was applied to extract and quantify root architectural traits of adult, field-grown maize plants. The relationships between root diameter and other root architectural characteristics are analysed for two maize cultivars. Key Results The basal diameter of the lateral roots (orders 1–3) was highly variable. Basal diameter was partly determined by the diameter of the bearing segment. Basal diameter defined a potential root length, but the lengths of most roots fell far short of this. This was explained partly by differences in the pattern of diameter change along roots. Diameter tended to decrease along most roots, with the steepness of the gradient of decrease depending on basal diameter. The longest roots were those that maintained (or sometimes increased) their diameters during elongation. The branching density (cm–1) of laterals was also determined by the diameter of the bearing segment. However, the location of this bearing segment along the mother root was also involved – intermediate positions were associated with higher densities of laterals. Conclusions The method used here allows us to obtain very detailed records of the geometry and topology of a complex root system. Basal diameter and the pattern of diameter change along a root were associated with its final length. These relationships are especially useful in simulations of root elongation and branching in source–sink models. PMID:26744490

[Effects of postponed basal nitrogen application with reduced nitrogen rate on grain yield and nitrogen use efficiency of south winter wheat].

PubMed

Zhang, Lei; Shao, Yu Hang; Gu, Shi Lu; Hu, Hang; Zhang, Wei Wei; Tian, Zhong Wei; Jiang, Dong; Dai, Ting Bo

2016-12-01

Excessive nitrogen (N) fertilizer application has led to a reduction of nitrogen use efficiency and environmental problems. It was of great significance for high-yield and high-efficiency cultivation to reduce N fertilizer application with modified application strategies. A two-year field experiment was conducted to study effects of different N application rates at basal and seedling application stages on grain yield and nitrogen use efficiency. Taking the conventional nitrogen application practice (240 kg N·hm -2 with application at basal, jointing, and booting stages at ratios of 5:3:2, respectively) as control, a field trial was conducted at different N application rates (240, 180 and 150 kg N·hm -2 , N 240 , N 180 and N 150 , respectively) and different application times [basal (L 0 ), fourth (L 4 ) and sixth leaf stage (L 6 )] to investigate the effects on grain yield and nitrogen use efficiency. The results indicated that grain yield decreased along with reducing the N application rate, but it had no significant difference between N 240 and N 180 while decreased significantly under N 150 . Nitrogen agronomy and recovery efficiency were all highest under N 180 . Among different N application stages, grain yield and nitrogen use efficiency were highest under L 4 . N 180 L 4 had no signifi-cant difference with control in grain yield, but its nitrogen use efficiency was significantly higher. The leaf area index, flag leaf photosynthesis rate, leaf nitrogen content, activity of nitrogen reductase and glutamine synthase in flag leaf, dry matter and N accumulation after jointing of N 180 L 4 had no significant difference with control. In an overall view, postponing basal N fertilizer application at reduced nitrogen rate could maintain high yield and improve nitrogen use efficiency through improving photosynthetic production capacity and promoting nitrogen uptake and assimilation.

Dehydroepiandrosterone Attenuates Cocaine-Seeking Behaviour Independently of Corticosterone Fluctuations.

PubMed

Maayan, R; Hirsh, L; Yadid, G; Weizman, A

2015-11-01

The neurosteroid dehydroepiandrosterone (DHEA) is involved in the pathophysiology of several psychiatric disorders, including cocaine addiction. We have previously shown that DHEA attenuates cocaine-seeking behaviour, and also that DHEA decreases corticosterone (CORT) levels in plasma and the prefrontal cortex. Previous studies have found that rats demonstrate cocaine-seeking behaviour only when the level of CORT reaches a minimum threshold. In the present study, we investigated whether the attenuating effect of DHEA on cocaine seeking is a result of it reducing CORT levels rather than a result of any unique neurosteroid properties. Rats received either daily DHEA injections (2 mg/kg, i.p.) alone, daily DHEA (2 mg/kg, i.p.) with CORT infusion (to maintain stable basal levels of CORT; 15 mg/kg, s.c.) or vehicle (i.p.) as control, throughout self-administration training and extinction sessions. We found that both DHEA-treated and DHEA + CORT-treated groups showed a significantly lower number of active lever presses compared to controls throughout training and extinction sessions, as well as at cocaine-primed reinstatement. DHEA-treated rats showed lower CORT levels throughout the experimental phases compared to DHEA + CORT-treated and control rats. Additionally, we show that DHEA administered to cocaine-trained rats throughout extinction sessions, or immediately before reinstatement, attenuated cocaine seeking. These findings indicate that DHEA attenuates cocaine-seeking behaviour independently of fluctuations in CORT levels. © 2015 British Society for Neuroendocrinology.

Effect of dietary vitamin E on the sperm quality of turbot ( Scophthalmus maximus)

NASA Astrophysics Data System (ADS)

Xu, Houguo; Huang, Lina; Liang, Mengqing; Zheng, Keke; Wang, Xinxing

2015-08-01

A 3-month feeding experiment was conducted in an in-door seawater system to investigate the effect of dietary vitamin E (Ve) on the sperm quality of turbot ( Scophthalmus maximus). D-α-tocopherol acetate was supplemented to the basal (control) diet (65.14 mg kg-1 Ve) to obtain low and high levels of dietary Ve (244.60 mg kg-1, LVe; 721.60 mg kg-1, HVe). Compared with the control, sperm concentration was significantly increased in Ve-supplemented groups (LVe and HVe); while relative sperm volume and testis-somatic index were significantly increased in group HVe only. Sperm motility duration was significantly longer in group HVe than in the control, but no significant difference was observed in percent motility among groups. Sperm size, the uniformity of mitochondrial size, and the integrity of mitochondria cristae and plasma membrane were improved by dietary Ve, especially in HVe. The content of Ve in testis and liver as well as polyunsaturated fatty acids in sperm increased with dietary Ve. These results suggested that dietary Ve, especially at the high level (721.60 mg kg-1), significantly improved sperm concentration and motility duration and maintained normal sperm morphology of turbot.

Shortleaf pine reproduction abundance and growth in pine-oak stands in the Missouri Ozarks

Treesearch

Elizabeth M. Blizzard; Doyle Henken; John M. Kabrick; Daniel C. Dey; David R. Larsen; David Gwaze

2007-01-01

We conducted an operational study to evaluate effect of site preparation treatments on pine reproduction density and the impact of overstory basal area and understory density on pine reproduction height and basal diameter in pine-oak stands in the Missouri Ozarks. Stands were harvested to or below B-level stocking, but patchiness of the oak decline lead to some plots...

Influence of residual basal area on longleaf pine (Pinus palustris Mill.) first year germination and establishment under selection silviculture

Treesearch

Ferhat Kara; Edward F. Loewenstein

2015-01-01

Even-aged silvicultural methods have been successfully used to manage longleaf pine (Pinus palustris Mill.) forests for wood production; however, successful use of uneven-aged methods to manage this ecosystem is less well documented. In this study, the effects of varying levels of residual basal area (RBA) (9.2, 13.8, and 18.4 m2...

Increased nitric oxide production in platelets from severe chronic renal failure patients.

PubMed

Siqueira, Mariana Alves de Sá; Brunini, Tatiana M C; Pereira, Natália Rodrigues; Martins, Marcela Anjos; Moss, Monique Bandeira; Santos, Sérgio F; Lugon, Jocemir R; Mendes-Ribeiro, Antônio C

2011-02-01

Nitric oxide (NO) production occurs through oxidation of the amino acid L-arginine by NO synthase (NOS). NO inhibits platelet activation by increasing the levels of cyclic guanosine monophosphate (cGMP), thus maintaining vascular homeostasis. Our group previously demonstrated (da Silva et al. 2005) an enhancement of the L-arginine-NO-cGMP pathway in platelets taken from chronic renal failure (CRF) patients on haemodialysis associated with reduced platelet aggregation. We investigate the platelet L-arginine-NO-cGMP pathway, platelet function, and inflammation from patients in CRF on conservative treatment. A total of 42 CRF patients and 42 controls (creatinine clearance = 27 ± 3 vs. 93 ± 1 mL per min per 1.73 m2, respectively) participated in this study. NOS activity and expression and cGMP concentration were measured in platelets. Platelet aggregation induced by collagen or ADP was evaluated and plasma levels of fibrinogen were determined by the Clauss method. A marked increase in basal NOS activity was seen in undialysed CRF patients compared with controls, accompanied by an elevation of fibrinogen plasma levels. There were no differences in expression of NOS and in cGMP levels. In this context, platelet aggregation was not affected. We provide the first evidence of increased intraplatelet NO biosynthesis in undialysed CRF patients, which can be an early marker of future haemostatic abnormalities during dialysis treatment.

Muscle satellite cells adopt divergent fates

PubMed Central

Zammit, Peter S.; Golding, Jon P.; Nagata, Yosuke; Hudon, Valérie; Partridge, Terence A.; Beauchamp, Jonathan R.

2004-01-01

Growth, repair, and regeneration of adult skeletal muscle depends on the persistence of satellite cells: muscle stem cells resident beneath the basal lamina that surrounds each myofiber. However, how the satellite cell compartment is maintained is unclear. Here, we use cultured myofibers to model muscle regeneration and show that satellite cells adopt divergent fates. Quiescent satellite cells are synchronously activated to coexpress the transcription factors Pax7 and MyoD. Most then proliferate, down-regulate Pax7, and differentiate. In contrast, other proliferating cells maintain Pax7 but lose MyoD and withdraw from immediate differentiation. These cells are typically located in clusters, together with Pax7−ve progeny destined for differentiation. Some of the Pax7+ve/MyoD−ve cells then leave the cell cycle, thus regaining the quiescent satellite cell phenotype. Significantly, noncycling cells contained within a cluster can be stimulated to proliferate again. These observations suggest that satellite cells either differentiate or switch from terminal myogenesis to maintain the satellite cell pool. PMID:15277541

Sea-Level Projections from the SeaRISE Initiative

NASA Technical Reports Server (NTRS)

Nowicki, Sophie; Bindschadler, Robert

2011-01-01

SeaRISE (Sea-level Response to Ice Sheet Evolution) is a community organized modeling effort, whose goal is to inform the fifth IPCC of the potential sea-level contribution from the Greenland and Antarctic ice sheets in the 21st and 22nd century. SeaRISE seeks to determine the most likely ice sheet response to imposed climatic forcing by initializing an ensemble of models with common datasets and applying the same forcing to each model. Sensitivity experiments were designed to quantify the sea-level rise associated with a change in: 1) surface mass balance, 2) basal lubrication, and 3) ocean induced basal melt. The range of responses, resulting from the multi-model approach, is interpreted as a proxy of uncertainty in our sea-level projections. http://websrv.cs .umt.edu/isis/index.php/SeaRISE_Assessment.

AtNUDT7, a Negative Regulator of Basal Immunity in Arabidopsis, Modulates Two Distinct Defense Response Pathways and Is Involved in Maintaining Redox Homeostasis1[C][OA

PubMed Central

Ge, Xiaochun; Li, Guo-Jing; Wang, Sheng-Bing; Zhu, Huifen; Zhu, Tong; Wang, Xun; Xia, Yiji

2007-01-01

Plants have evolved complicated regulatory systems to control immune responses. Both positive and negative signaling pathways interplay to coordinate development of a resistance response with the appropriate amplitude and duration. AtNUDT7, a Nudix domain-containing protein in Arabidopsis (Arabidopsis thaliana) that hydrolyzes nucleotide derivatives, was found to be a negative regulator of the basal defense response, and its loss-of-function mutation results in enhanced resistance to infection by Pseudomonas syringae. The nudt7 mutation does not cause a strong constitutive disease resistance phenotype, but it leads to a heightened defense response, including accelerated activation of defense-related genes that can be triggered by pathogenic and nonpathogenic microorganisms. The nudt7 mutation enhances two distinct defense response pathways: one independent of and the other dependent on NPR1 and salicylic acid accumulation. In vitro enzymatic assays revealed that ADP-ribose and NADH are preferred substrates of NUDT7, and the hydrolysis activity of NUDT7 is essential for its biological function and is sensitive to inhibition by Ca2+. Further analyses indicate that ADP-ribose is not likely the physiological substrate of NUDT7. However, the nudt7 mutation leads to perturbation of cellular redox homeostasis and a higher level of NADH in pathogen-challenged leaves. The study suggests that the alteration in cellular antioxidant status caused by the nudt7 mutation primes the cells for the amplified defense response and NUDT7 functions to modulate the defense response to prevent excessive stimulation. PMID:17660350

Vitamin C modulates cadmium-induced hepatic antioxidants' gene transcripts and toxicopathic changes in Nile tilapia, Oreochromis niloticus.

PubMed

El-Sayed, Yasser S; El-Gazzar, Ahmed M; El-Nahas, Abeer F; Ashry, Khaled M

2016-01-01

Cadmium (Cd) is one of the naturally occurring heavy metals having adverse effects, while vitamin C (L-ascorbic acid) is an essential micronutrient for fish, which can attenuate tissue damage owing to its chain-breaking antioxidant and free radical scavenger properties. The adult Nile tilapia fish were exposed to Cd at 5 mg/l with and without vitamin C (500 mg/kg diet) for 45 days in addition to negative and positive controls fed with the basal diet and basal diet supplemented with vitamin C, respectively. Hepatic relative mRNA expression of genes involved in antioxidant function, metallothionein (MT), glutathione S-transferase (GST-α1), and glutathione peroxidase (GPx1), was assessed using real-time reverse transcription polymerase chain reaction (RT-PCR). Hepatic architecture was also histopathologically examined. Tilapia exposed to Cd exhibited upregulated antioxidants' gene transcript levels, GST-⍺1, GPx1, and MT by 6.10-, 4.60-, and 4.29-fold, respectively. Histopathologically, Cd caused severe hepatic changes of multifocal hepatocellular and pancreatic acinar necrosis, and lytic hepatocytes infiltrated with eosinophilic granular cells. Co-treatment of Cd-exposed fish with vitamin C overexpressed antioxidant enzyme-related genes, GST-⍺1 (16.26-fold) and GPx1 (18.68-fold), and maintained the expression of MT gene close to control (1.07-fold), averting the toxicopathic lesions induced by Cd. These results suggested that vitamin C has the potential to protect Nile tilapia from Cd hepatotoxicity via sustaining hepatic antioxidants' genes transcripts and normal histoarchitecture.

Activating and optimizing MoS 2 basal planes for hydrogen evolution through the formation of strained sulphur vacancies

DOE PAGES

Li, Hong; Tsai, Charlie; Koh, Ai Leen; ...

2015-11-09

As a promising non-precious catalyst for the hydrogen evolution reaction, molybdenum disulphide (MoS 2) is known to contain active edge sites and an inert basal plane. Activating the MoS 2 basal plane could further enhance its HER activity but is not often a strategy for doing so. Herein, we report the first activation and optimization of the basal plane of monolayer 2H-MoS 2 for HER by introducing sulphur (S) vacancies and strain. Our theoretical and experimental results show that the S-vacancies are new catalytic sites in the basal plane, where gap states around the Fermi level allow hydrogen to bindmore » directly to exposed Mo atoms. The hydrogen adsorption free energy (ΔG H) can be further manipulated by straining the surface with S-vacancies, which fine-tunes the catalytic activity. Furthermore, proper combinations of S-vacancy and strain yield the optimal ΔG H = 0 eV, which allows us to achieve the highest intrinsic HER activity among molybdenum-sulphide-based catalysts.« less

Modeling the Effects of Fire Frequency and Severity on Forests in the Northwestern United States

USGS Publications Warehouse

Busing, Richard T.; Solomon, Allen M.

2006-01-01

This study used a model of forest dynamics (FORCLIM) and actual forest survey data to demonstrate the effects of various fire regimes on different forest types in the Pacific Northwest. We examined forests in eight ecoregions ranging from wet coastal forests dominated by Pseudotsuga menziesii and other tall conifers to dry interior forests dominated by Pinus ponderosa. Fire effects simulated as elevated mortality of trees based on their species and size did alter forest structure and species composition. Low frequency fires characteristic of wetter forests (return interval >200 yr) had minor effects on composition. When fires were severe, they tended to reduce total basal area with little regard to species differences. High frequency fires characteristic of drier forests (return interval <30 yr) had major effects on species composition and on total basal area. Typically, they caused substantial reductions in total basal area and shifts in dominance toward highly fire tolerant species. With the addition of fire, simulated basal areas averaged across ecoregions were reduced to levels approximating observed basal areas.

Basal body assembly in ciliates: the power of numbers

PubMed Central

Pearson, Chad G.; Winey, Mark

2009-01-01

Centrioles perform the dual functions of organizing both centrosomes and cilia. The biogenesis of nascent centrioles is an essential cellular event that is tightly coupled to the cell cycle so that each cell contains only two or four centrioles at any given point in the cell cycle. The assembly of centrioles and their analogs, basal bodies, is well characterized at the ultrastructural level whereby structural modules are built into a functional organelle. Genetic studies in model organisms combined with proteomic, bioinformatic, and identifying ciliary disease gene orthologs have revealed a wealth of molecules requiring further analysis to determine their roles in centriole duplication, assembly, and function. Nonetheless, at this stage our understanding of how molecular components interact to build new centrioles and basal bodies is limited. The ciliates, Tetrahymena and Paramecium, historically have been the subject of cytological and genetic study of basal bodies. Recent advances in the ciliate genetic and molecular toolkit have placed these model organisms in a favorable position to study the molecular mechanisms of centriole and basal body assembly. PMID:19192246

Functional Feed Assessment on Litopenaeus vannamei Using 100% Fish Meal Replacement by Soybean Meal, High Levels of Complex Carbohydrates and Bacillus Probiotic Strains

PubMed Central

Olmos, Jorge; Ochoa, Leonel; Paniagua-Michel, Jesus; Contreras, Rosalia

2011-01-01

Functional feed supplemented with alternative-economic nutrient sources (protein, carbohydrates, lipids) and probiotics are being considered in shrimp/fish aquaculture production systems as an option to increase yield and profits and to reduce water pollution. In this study the probiotic potential to formulate functional feeds have been evaluated using four dietary treatments: Treatment 1 (B + Bs); Bacillus subtilis potential probiotic strain was supplemented to a soybeanmeal (SBM)—carbohydrates (CHO) basal feed. Treatment 2 (B + Bm); Bacillus megaterium potential probiotic strain was supplemented to the same SBM-CHO basal feed. In Treatment 3 (B); SBM-CHO basal feed was not supplemented with probiotic strains. Treatment 4 (C); fishmeal commercial feed (FM) was utilized as positive control. Feeding trials evaluated the survival, growth, and food conversion ratio and stress tolerance of juvenile Litopenaeus vannamei (Boone) Pacific white shrimp. Best overall shrimp performance was observed for animals fed with Treatment 1 (B+Bs); additionally, stress tolerance and hemolymph metabolites also showed the best performance in this treatment. SBM-CHO basal feed not supplemented with probiotic strains (B) presented smaller growth and lower feed conversion ratio (FCR). Shrimps fed with the fishmeal commercial feed (C) presented the lowest stress tolerance to high ammonia and low oxygen levels. Specifically selected B. subtilis strains are recommended to formulate functional and economical feeds containing high levels of vegetable; protein and carbohydrates as main dietary sources in L. vannamei cultures. PMID:21747750

Functional feed assessment on Litopenaeus vannamei using 100% fish meal replacement by soybean meal, high levels of complex carbohydrates and Bacillus probiotic strains.

PubMed

Olmos, Jorge; Ochoa, Leonel; Paniagua-Michel, Jesus; Contreras, Rosalia

2011-01-01

Functional feed supplemented with alternative-economic nutrient sources (protein, carbohydrates, lipids) and probiotics are being considered in shrimp/fish aquaculture production systems as an option to increase yield and profits and to reduce water pollution. In this study the probiotic potential to formulate functional feeds have been evaluated using four dietary treatments: Treatment 1 (B + Bs); Bacillus subtilis potential probiotic strain was supplemented to a soybeanmeal (SBM)-carbohydrates (CHO) basal feed. Treatment 2 (B + Bm); Bacillus megaterium potential probiotic strain was supplemented to the same SBM-CHO basal feed. In Treatment 3 (B); SBM-CHO basal feed was not supplemented with probiotic strains. Treatment 4 (C); fishmeal commercial feed (FM) was utilized as positive control. Feeding trials evaluated the survival, growth, and food conversion ratio and stress tolerance of juvenile Litopenaeus vannamei (Boone) Pacific white shrimp. Best overall shrimp performance was observed for animals fed with Treatment 1 (B+Bs); additionally, stress tolerance and hemolymph metabolites also showed the best performance in this treatment. SBM-CHO basal feed not supplemented with probiotic strains (B) presented smaller growth and lower feed conversion ratio (FCR). Shrimps fed with the fishmeal commercial feed (C) presented the lowest stress tolerance to high ammonia and low oxygen levels. Specifically selected B. subtilis strains are recommended to formulate functional and economical feeds containing high levels of vegetable; protein and carbohydrates as main dietary sources in L. vannamei cultures.

An Interesting Case of Basal Cell Carcinoma with Raynaud's Phenomenon Following Chronic Arsenic Exposure.

PubMed

Gulshan, S; Rahman, M J; Sarkar, R; Ghosh, S; Hazra, R

2016-01-01

Arsenic is commonly known to be associated with squamous cell carcinoma. Among the lesser known associations is basal cell carcinoma and even rarer is its effect on blood vessels causing peripheral vascular disease. Here we present a case of a 55 yr old man with ulceroproliferative lesions on scalp and forehead along with several hyperpigmented patches on trunk and extremities. He had symptoms suggestive of Raynaud's phenomenon that eventually led to digital gangrene. FNAC was done which was suggestive of basal cell carcinoma. On further enquiry, he was found to reside in an arsenic endemic zone and was investigated for blood arsenic level which was elevated. Punch biopsy from different lesions from body confirmed nodular basal cell carcinoma. Presently the patient has stopped drinking water from the local tubewell. On follow-up he shows improvement of Raynaud's phenomenon and skin lesions.

Complementary acupuncture in Parkinson's disease: a spect study.

PubMed

Huang, Yong; Jiang, Xuemei; Zhuo, Ying; Wik, Gustav

2010-02-01

We studied cerebral effects of complementary acupuncture in Parkinson's disease using single photon emission computed tomography (SPECT) measures of 99mTc-ECD and 99mTc-TRODAT-4, before and after five weeks of treatment. Ten patients were randomly assigned to receive levodopa alone (controls) or levodopa and complementary scalp electro-acupuncture. Before treatment, no hemispheric regional cerebral blood flow (rCBF) differences were found, whereas striatal dopamine transporter (DAT) activity was lower in the most affected hemisphere. Treatment with levodopa alone did not change rCBF, whereas it increased basal ganglion DAT activity in the most affected hemisphere. Patients who received levodopa and complementary acupuncture had increased rCBF in the frontal lobe, the occipital lobe, the basal ganglion, and the cerebellum in the most affected hemisphere as compared to baseline, but there were no changes in basal ganglia DAT levels. Thus, complementary acupuncture treatment in Parkinson's disease may affect rCBF but not basal ganglion DAT.

A20 Regulates Atherogenic Interferon (IFN)-γ Signaling in Vascular Cells by Modulating Basal IFNβ Levels*

PubMed Central

Moll, Herwig P.; Lee, Andy; Minussi, Darlan C.; da Silva, Cleide G.; Csizmadia, Eva; Bhasin, Manoj; Ferran, Christiane

2014-01-01

IFNγ signaling in endothelial (EC) and smooth muscle cells (SMC) is a key culprit of pathologic vascular remodeling. The impact of NF-κB inhibitory protein A20 on IFNγ signaling in vascular cells remains unknown. In gain- and loss-of-function studies, A20 inversely regulated expression of IFNγ-induced atherogenic genes in human EC and SMC by modulating STAT1 transcription. In vivo, inadequate A20 expression in A20 heterozygote mice aggravated intimal hyperplasia following partial carotid artery ligation. This outcome uniquely associated with increased levels of Stat1 and super-induction of Ifnγ-dependent genes. Transcriptome analysis of the aortic media from A20 heterozygote versus wild-type mice revealed increased basal Ifnβ signaling as the likely cause for higher Stat1 transcription. We confirmed higher basal IFNβ levels in A20-silenced human SMC and showed that neutralization or knockdown of IFNβ abrogates heightened STAT1 levels in these cells. Upstream of IFNβ, A20-silenced EC and SMC demonstrated higher levels of phosphorylated/activated TANK-binding kinase-1 (TBK1), a regulator of IFNβ transcription. This suggested that A20 knockdown increased STAT1 transcription by enhancing TBK1 activation and subsequently basal IFNβ levels. Altogether, these results uncover A20 as a key physiologic regulator of atherogenic IFNγ/STAT1 signaling. This novel function of A20 added to its ability to inhibit nuclear factor-κB (NF-κB) activation solidifies its promise as an ideal therapeutic candidate for treatment and prevention of vascular diseases. In light of recently discovered A20/TNFAIP3 (TNFα-induced protein 3) single nucleotide polymorphisms that impart lower A20 expression or function, these results also qualify A20 as a reliable clinical biomarker for vascular risk assessment. PMID:25217635

Statistical Analysis of Readthrough Levels for Nonsense Mutations in Mammalian Cells Reveals a Major Determinant of Response to Gentamicin

PubMed Central

Floquet, Célia; Hatin, Isabelle; Rousset, Jean-Pierre; Bidou, Laure

2012-01-01

The efficiency of translation termination depends on the nature of the stop codon and the surrounding nucleotides. Some molecules, such as aminoglycoside antibiotics (gentamicin), decrease termination efficiency and are currently being evaluated for diseases caused by premature termination codons. However, the readthrough response to treatment is highly variable and little is known about the rules governing readthrough level and response to aminoglycosides. In this study, we carried out in-depth statistical analysis on a very large set of nonsense mutations to decipher the elements of nucleotide context responsible for modulating readthrough levels and gentamicin response. We quantified readthrough for 66 sequences containing a stop codon, in the presence and absence of gentamicin, in cultured mammalian cells. We demonstrated that the efficiency of readthrough after treatment is determined by the complex interplay between the stop codon and a larger sequence context. There was a strong positive correlation between basal and induced readthrough levels, and a weak negative correlation between basal readthrough level and gentamicin response (i.e. the factor of increase from basal to induced readthrough levels). The identity of the stop codon did not affect the response to gentamicin treatment. In agreement with a previous report, we confirm that the presence of a cytosine in +4 position promotes higher basal and gentamicin-induced readthrough than other nucleotides. We highlight for the first time that the presence of a uracil residue immediately upstream from the stop codon is a major determinant of the response to gentamicin. Moreover, this effect was mediated by the nucleotide itself, rather than by the amino-acid or tRNA corresponding to the −1 codon. Finally, we point out that a uracil at this position associated with a cytosine at +4 results in an optimal gentamicin-induced readthrough, which is the therapeutically relevant variable. PMID:22479203

Inhibition of muscarinic receptor-induced inositol phospholipid hydrolysis by caffeine, beta-adrenoceptors and protein kinase C in intestinal smooth muscle.

PubMed Central

Prestwich, S A; Bolton, T B

1995-01-01

1. The effects of caffeine, isoprenaline, dibutyryl cyclic AMP, isobutylmethylxanthine (IBMX), 12-O-tetradecanoylphorbol-13-acetate (TPA) or 1-oleoyl-2-acetylglycerol (OAG), (protein kinase C (PKC) activators), 2-methoxy verapamil (D600), thapsigargin and ryanodine on muscarinic acetylcholine receptor (AChR)-stimulated inositol phospholipid hydrolysis were studied in smooth muscle fragments from the longitudinal layer of the small intestine of the guinea-pig. 2. Incubation of the fragments with the muscarinic agonist, carbachol (CCh) (100 microM) resulted in rapid increases in the levels of all the inositol phosphate isomers with maximal increases in the [3H]-inositol (1,4,5) trisphosphate ([3H]-Ins(1,4,5)P3) isomer occurring 10 s following incubation. 3. The beta-adrenoceptor agonist, isoprenaline (10 microM) and dibutyryl cyclic AMP (10 microM), a membrane permeant analogue of cyclic AMP both reduced the CCh stimulation, but not the basal levels of [3H]-inositol phosphates. This inhibition by dibutyryl cyclic AMP was enhanced in the presence of the phosphodiesterase inhibitor, IBMX. CCh inhibited the isoprenaline-induced increases in the levels of cyclic AMP and this was via a pertussi toxin (PTX)-sensitive G-protein mechanism. 4. TPA (1 microM) and OAG (100 microM) a 1,2-diacylglycerol (DAG) analogue both reduced the CCh-induced increases in [3H]-inositol phosphates levels but neither affected basal values nor the basal levels of cyclic AMP. 5. D600 (10 microM), which blocks voltage-dependent Ca2+ channels, also reduced the CCh-stimulated levels of [3H]-inositol phosphates suggesting that some of the agonist-induced increases are due to a potentiating effect of Ca2+ entering the cell. 6. Caffeine (0.5-30 mM) significantly inhibited both the basal and CCh-induced increases in all the [3H]-inositol phosphate isomers. Its inhibitory action was not due to increases in cyclic AMP since caffeine had no effect on the levels of cyclic AMP at concentrations up to 30 mM. 7. Incubation with thapsigargin (1 microM) and ryanodine (10 microM) had no effect on either basal or CCh-induced inositol phospholipid hydrolysis or cyclic AMP levels. 8. The results indicate a reciprocal inhibition by beta-adrenoceptors and muscarinic AChRs of their effects on cyclic AMP and inositol phosphate levels respectively. Ca2+ entering the cell (but not the action of ryanodine or thapsigargin) potentiates while caffeine inhibits muscarinic AChR-induced rises in inositol phosphate levels. Diacylglycerols may exert a negative feedback inhibition on inositol phosphate production. PMID:7537591

Transducing Airway Basal Cells with a Helper-Dependent Adenoviral Vector for Lung Gene Therapy.

PubMed

Cao, Huibi; Ouyang, Hong; Grasemann, Hartmut; Bartlett, Claire; Du, Kai; Duan, Rongqi; Shi, Fushan; Estrada, Marvin; Seigel, Kyle E; Coates, Allan L; Yeger, Herman; Bear, Christine E; Gonska, Tanja; Moraes, Theo J; Hu, Jim

2018-06-01

A major challenge in developing gene-based therapies for airway diseases such as cystic fibrosis (CF) is sustaining therapeutic levels of transgene expression over time. This is largely due to airway epithelial cell turnover and the host immunogenicity to gene delivery vectors. Modern gene editing tools and delivery vehicles hold great potential for overcoming this challenge. There is currently not much known about how to deliver genes into airway stem cells, of which basal cells are the major type in human airways. In this study, helper-dependent adenoviral (HD-Ad) vectors were delivered to mouse and pig airways via intranasal delivery, and direct bronchoscopic instillation, respectively. Vector transduction was assessed by immunostaining of lung tissue sections, which revealed that airway basal cells of mice and pigs can be targeted in vivo. In addition, efficient transduction of primary human airway basal cells was verified with an HD-Ad vector expressing green fluorescent protein. Furthermore, we successfully delivered the human CFTR gene to airway basal cells from CF patients, and demonstrated restoration of CFTR channel activity following cell differentiation in air-liquid interface culture. Our results provide a strong rationale for utilizing HD-Ad vectors to target airway basal cells for permanent gene correction of genetic airway diseases.

Mitogen-activated protein kinases participate in determination of apical-basal symmetry in Pisum sativum.

PubMed

Winnicki, Konrad; Polit, Justyna Teresa; Żabka, Aneta; Maszewski, Janusz

2017-03-01

Mitogen-activated protein kinases (MAPKs) are implicated in various processes in plants. Apart from response to biotic and abiotic stresses they are involved in regulation of embryo development. Although MAPKs were found to be indispensable during embryo development it has never been established at which stages of embryogenesis and in which regions of a plant embryo activated MAPKs can be observed. Here, we show that apical and basal regions display activation of the same types of MAPKs and the only difference concerns the level of their phosphorylation and cellular localization. Dually-phosphorylated MAPKs were found in nuclei of the apical region of an embryo both at the early and late cotyledonary stage while no immunofluorescence signals were detected in nuclei of the basal region. However, in this case phosphorylated MAPKs were immunodetected in cytoplasm in the apical domain of cortex cells, indicating their role in auxin transport from the basal to apical region of an embryo. Furthermore, obtained data indicate that nuclear localization of activated MAPKs may result from epigenetic modifications and polar auxin transport. The presented data and previous studies lead to the conclusion that activated MAPKs and their cellular localization define apical and basal regions during formation of an apical-basal axis. Copyright © 2017 Elsevier B.V. All rights reserved.

Neurochemical evidence that cocaine- and amphetamine-regulated transcript (CART) 55-102 peptide modulates the dopaminergic reward system by decreasing the dopamine release in the mouse nucleus accumbens.

PubMed

Rakovska, Angelina; Baranyi, Maria; Windisch, Katalin; Petkova-Kirova, Polina; Gagov, Hristo; Kalfin, Reni

2017-09-01

CART (Cocaine- and Amphetamine-Regulated Transcript) peptide is a neurotransmitter naturally occurring in the CNS and found mostly in nucleus accumbens, ventrotegmental area, ventral pallidum, amygdalae and striatum, brain regions associated with drug addiction. In the nucleus accumbens, known for its significant role in motivation, pleasure, reward and reinforcement learning, CART peptide inhibits cocaine and amphetamine-induced dopamine-mediated increases in locomotor activity and behavior, suggesting a CART peptide interaction with the dopaminergic system. Thus in the present study, we examined the effect of CART (55-102) peptide on the basal, electrical field stimulation-evoked (EFS-evoked) (30V, 2Hz, 120 shocks) and returning basal dopamine (DA) release and on the release of the DA metabolites 3,4-dihydroxyphenyl acetaldehyde (DOPAL), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3,4-dihydroxyphenylethanol (DOPET), 3-methoxytyramine (3-MT) as well as on norepinephrine (NE) and dopamine-o-quinone (Daq) in isolated mouse nucleus accumbens, in a preparation, in which any CART peptide effects on the dendrites or soma of ventral tegmental projection neurons have been excluded. We further extended our study to assess the effect of CART (55-102) peptide on basal cocaine-induced release of dopamine and its metabolites DOPAL, DOPAC, HVA, DOPET and 3-MT as well as on NE and Daq. To analyze the amount of [ 3 H]dopamine, dopamine metabolites, Daq and NE in the nucleus accumbens superfusate, a high-pressure liquid chromatography (HPLC), coupled with electrochemical, UV and radiochemical detections was used. CART (55-102) peptide, 0.1μM, added alone, exerted: (i) a significant decrease in the basal and EFS-evoked levels of extracellular dopamine (ii) a significant increase in the EFS-evoked and returning basal levels of the dopamine metabolites DOPAC and HVA, major products of dopamine degradation and (iii) a significant decrease in the returning basal levels of DOPET. At the same concentration, 0.1μM, CART (55-102) peptide did not have any effect on the release of noradrenaline. In the presence of CART (55-102) peptide, 0.1μM, the effect of cocaine, 30μM, on the basal dopamine release was inhibited and the effect on the basal DOPAC release substantially increased. To our knowledge, our findings are the first to show direct neurochemical evidence that CART (55-102) peptide plays a neuromodulatory role on the dopaminergic reward system by decreasing dopamine in the mouse nucleus accumbens and by attenuating cocaine-induced effects on dopamine release. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of dietary supplementation of l-tryptophan on thermal tolerance and oxygen consumption rate in Cirrhinus mrigala fingerlings under varied stocking density.

PubMed

Tejpal, C S; Sumitha, E B; Pal, A K; Shivananda Murthy, H; Sahu, N P; Siddaiah, G M

2014-04-01

A 60 day feeding trial was conducted to study the effect of dietary l-tryptophan on thermal tolerance and oxygen consumption rate of freshwater fish, mrigala, Cirrhinus mrigala reared under ambient temperature at low and high stocking density. Four hundred eighty fingerlings were distributed into eight experimental groups. Four groups each of low density group (10 fishes/75L water) and higher density group (30 fishes/75L water) were fed a diet containing 0, 0.68, 1.36 or 2.72% l-tryptophan in the diet, thus forming eight experimental groups namely, Low density control (LC) (basal feed +0% l-tryptophan); LT1 (basal feed+0.68% l-tryptophan); LT2 (basal feed+1.36% l-tryptophan); LT3 (basal feed+2.72% l-tryptophan); high density control (HC) (basal feed+0% l-tryptophan); HT1 (basal feed+0.68% l-tryptophan); HT2 (basal feed+1.36% l-tryptophan); and HT3 (basal feed+2.72% l-tryptophan) were fed at 3% of the body weight. The test diets having crude protein 34.33±0.23 to 35.81±0.18% and lipid 423.49±1.76 to 425.85±0.31KCal/100g were prepared using purified ingredients. The possible role of dietary l-tryptophan on thermal tolerance and oxygen consumption rate was assessed in terms of critical thermal maxima (CTMax), critical thermal minima (CTMin), lethal thermal maxima (LTMax) and lethal thermal minima (LTMin). The CTMax, CTMin, LTMax and LTMin values were found to be significantly higher (p<0.05) in the treatment groups with CTMax 42.94±0.037 (LT2); LT Max 43.18±0.070 (LT2); CTMin 10.47±0.088 (LT2) and LTMin 9.42±0.062 (LT3), whereas the control group showed a lower tolerance level. The same trend was observed in the high density group (CTMax 42.09±0.066 (LT3); LTMax 43 23±0.067 (HT3); CTMin 10.98±0.040 (HT3) and LTMin 9.74±0.037 (HT3). However, gradual supplementation of dietary l-tryptophan in the diet significantly reduced the oxygen consumption rate in both the low density group (Y=-26.74x+222.4, r²=0.915) and the high density group (Y=-32.96x+296.5, r²=0.8923). Dietary supplementation of l-tryptophan at a level of 1.36% improved the thermal tolerance level and reduced the oxygen consumption rate in C. mrigala fingerlings. Copyright © 2014 Elsevier Ltd. All rights reserved.

Rapamycin regulates autophagy and cell adhesion in induced pluripotent stem cells.

PubMed

Sotthibundhu, Areechun; McDonagh, Katya; von Kriegsheim, Alexander; Garcia-Munoz, Amaya; Klawiter, Agnieszka; Thompson, Kerry; Chauhan, Kapil Dev; Krawczyk, Janusz; McInerney, Veronica; Dockery, Peter; Devine, Michael J; Kunath, Tilo; Barry, Frank; O'Brien, Timothy; Shen, Sanbing

2016-11-15

Cellular reprogramming is a stressful process, which requires cells to engulf somatic features and produce and maintain stemness machineries. Autophagy is a process to degrade unwanted proteins and is required for the derivation of induced pluripotent stem cells (iPSCs). However, the role of autophagy during iPSC maintenance remains undefined. Human iPSCs were investigated by microscopy, immunofluorescence, and immunoblotting to detect autophagy machinery. Cells were treated with rapamycin to activate autophagy and with bafilomycin to block autophagy during iPSC maintenance. High concentrations of rapamycin treatment unexpectedly resulted in spontaneous formation of round floating spheres of uniform size, which were analyzed for differentiation into three germ layers. Mass spectrometry was deployed to reveal altered protein expression and pathways associated with rapamycin treatment. We demonstrate that human iPSCs express high basal levels of autophagy, including key components of APMKα, ULK1/2, BECLIN-1, ATG13, ATG101, ATG12, ATG3, ATG5, and LC3B. Block of autophagy by bafilomycin induces iPSC death and rapamycin attenuates the bafilomycin effect. Rapamycin treatment upregulates autophagy in iPSCs in a dose/time-dependent manner. High concentration of rapamycin reduces NANOG expression and induces spontaneous formation of round and uniformly sized embryoid bodies (EBs) with accelerated differentiation into three germ layers. Mass spectrometry analysis identifies actin cytoskeleton and adherens junctions as the major targets of rapamycin in mediating iPSC detachment and differentiation. High levels of basal autophagy activity are present during iPSC derivation and maintenance. Rapamycin alters expression of actin cytoskeleton and adherens junctions, induces uniform EB formation, and accelerates differentiation. IPSCs are sensitive to enzyme dissociation and require a lengthy differentiation time. The shape and size of EBs also play a role in the heterogeneity of end cell products. This research therefore highlights the potential of rapamycin in producing uniform EBs and in shortening iPSC differentiation duration.

Effect of N Fertilization Pattern on Rice Yield, N Use Efficiency and Fertilizer–N Fate in the Yangtze River Basin, China

PubMed Central

Liu, Xiaowei; Wang, Huoyan; Zhou, Jianmin; Hu, Fengqin; Zhu, Dejin; Chen, Zhaoming; Liu, Yongzhe

2016-01-01

High N loss and low N use efficiency (NUE), caused by high N fertilizer inputs and inappropriate fertilization patterns, have become important issues in the rice (Oryza sativa L.) growing regions of southern China. Changing current farmer fertilizer practice (FFP, 225 kg ha–1 N as three applications, 40% as basal fertilizer, 30% as tillering fertilizer and 30% as jointing fertilizer) to one—time root—zone fertilization (RZF, 225 kg ha–1 N applied once into 10 cm deep holes positioned 5 cm from the rice root as basal fertilizer) will address this problem. A two—year field experiment covering two rice growing regions was conducted to investigate the effect of urea one—time RZF on rice growth, nutrient uptake, and NUE. The highest NH4+–N content for RZF at fertilizer point at 30 d and 60 d after fertilization were 861.8 and 369.9 mg kg–1 higher than FFP, respectively. Rice yield and total N accumulation of RZF increased by 4.3–44.9% and 12.7–111.2% compared to FFP, respectively. RZF reduced fertilizer—N loss by 56.3–81.9% compared to FFP. The NUEs following RZF (mean of 65.8% for the difference method and 43.7% for the labelled method) were significantly higher than FFP (mean of 35.7% for the difference method and 14.4% for the labelled method). In conclusion, RZF maintained substantial levels of fertilizer—N in the root—zone, which led to enhanced rice biomass and N uptake during the early growth stages, increased fertilizer—N residual levels and reduced fertilizer—N loss at harvest. RZF produced a higher yield increment and showed an increased capacity to resist environmental threats than FFP in sandy soils. Therefore, adopting suitable fertilizer patterns plays a key role in enhancing agricultural benefits. PMID:27861491

An Imminent Revolution in Modeling Interactions of Ice Sheets With Climate

NASA Astrophysics Data System (ADS)

Hughes, T.

2008-12-01

Modeling continental ice sheets was inaugurated by meteorologists William Budd and Uwe Radok, with mathematician Richard Jenssen, in 1971. Their model calculated the thermal and mechanical regime using measured surface accumulation rates, temperatures, and elevations, and bed topography. This top-down approach delivered a basal thermal regime of temperatures or melting rates for an assumed basal geothermal heat flux. When Philippe Huybrechts and others incorporated time, largely unknownpast surface conditions had a major effect on present basal thermal conditions. This approach produced ice-sheet models with only a slow response to external forcing, whereas the glacial geological record and climate records from ice and ocean cores show that ice sheets can have rapid changes in size and shape independent of external forcing. These top-down models were wholly inadequate for reconstructing former ice sheets at the LGM for CLIMAP in 1981. Ice-sheet areas,elevations, and volumes provided the albedo, surface topography, and sea-surface area as input to climate models. A bottom-up model based on dated glacial geology was developed to provide the areal extent and basal thermal regime of ice sheets at the LGM. Basal thermal conditions determined ice-bed coupling and therefore the elevation of ice sheets. High convex ice surfaces for slow sheet flow lower about 20 percent when a frozen bed becomes thawed. As further basal melting drowns bedrock bumps that "pin" basal ice, the ice surface becomes concave in fast stream flow that ends as low floating ice shelves at marine ice margins. A revolution in modeling interactions between glaciation, climate, and sea level is driven by new Greenland and Antarctic data from Earth-orbiting satellites, airborne and surface traverses, and deep drilling. We anticipate continuous data acquisition of surface albedo, accumulation/ablation rates, elevations, velocities, and temperatures over a whole ice sheet, mapping basal thermal conditions by radar, seismic, and magnetic profiling, and direct measurement of basal conditions by deep drilling and coring into the ice and the bed. These data allow calculating the geothermal heat flux and mapping flow of basal meltwater from geothermal sources to sinks at the termini of ice streams, which discharge up to 90 percent of the ice. James Fastook has a preliminary solution of the full momentum equation needed to model ice streams. Douglas MacAyeal has pioneered modeling catastrophic ice-shelf disintegration that releases "armadas" of icebergs into the world ocean, to extract heat from ocean surface water and thereby reduce the critical ocean-to-atmosphere heat exchange that drives global climate. Ice sheets are the only component of Earth's climate machine that can destroy itself-- swiftly--and thereby radically and rapidly alter global climate and sea level.

Partial denervation of sub-basal axons persists following debridement wounds to the mouse cornea.

PubMed

Pajoohesh-Ganji, Ahdeah; Pal-Ghosh, Sonali; Tadvalkar, Gauri; Kyne, Briana M; Saban, Daniel R; Stepp, Mary Ann

2015-11-01

Although sensory reinnervation occurs after injury in the peripheral nervous system, poor reinnervation in the elderly and those with diabetes often leads to pathology. Here we quantify sub-basal axon density in the central and peripheral mouse cornea over time after three different types of injury. The mouse cornea is highly innervated with a dense array of sub-basal nerves that form a spiral called the vortex at the corneal center or apex; these nerves are readily detected within flat mounted corneas. After anesthesia, corneal epithelial cells were removed using either a dulled blade or a rotating burr within an area demarcated centrally with a 1.5 mm trephine. A third wound type, superficial trephination, involved demarcating the area with the 1.5 mm trephine but not removing cells. By 7 days after superficial trephination, sub-basal axon density returns to control levels; by 28 days the vortex reforms. Although axon density is similar to control 14 days after dulled blade and rotating burr wounding, defects in axon morphology at the corneal apex remain. After 14 days, axons retract from the center leaving the sub-basal axon density reduced by 37.2 and 36.8% at 28 days after dulled blade and rotating burr wounding, respectively, compared with control. Assessment of inflammation using flow cytometry shows that persistent inflammation is not a factor in the incomplete reinnervation. Expression of mRNAs encoding 22 regeneration-associated genes involved in axon targeting assessed by QPCR reveals that netrin-1 and ephrin signaling are altered after wounding. Subpopulations of corneal epithelial basal cells at the corneal apex stop expressing ki67 as early as 7 days after injury and by 14 and 28 days after wounding, many of these basal cells undergo apoptosis and die. Although sub-basal axons are restored to their normal density and morphology after superficial trephination, sub-basal axon recovery is partial after debridement wounds. The increase in corneal epithelial basal cell apoptosis at the apex observed at 14 days after corneal debridement may destabilize newly reinnervated sub-basal axons and lead to their retraction toward the periphery.

Hypoglycemia in patients with type 2 diabetes newly initiated on basal insulin in the US in a community setting: impact on treatment discontinuation and hospitalization.

PubMed

Dalal, Mehul R; Kazemi, Mahmood R; Ye, Fen

2017-02-01

To evaluate the impact of 6 month hypoglycemia on treatment discontinuation and hospitalization of patients initiating basal insulin for type 2 diabetes (T2D) in real-world practice. This was a retrospective cohort study of patient-level data using electronic medical records (EMRs) in the Predictive Health Intelligence diabetes dataset. Data from adult patients with T2D initiating basal insulin glargine, insulin detemir, or Neutral Protamine Hagedorn insulin between January 2008 and March 2014 was analyzed. The date of first basal insulin prescription in an outpatient setting was the index date. A 12 month baseline prior to the index date was established; follow-up was 6-24 months from the index date. Patients were assigned to cohorts by experience of hypoglycemia (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code or blood glucose test) in the first 6 months following the index date; with hypoglycemia and without hypoglycemia cohorts were compared for basal insulin treatment discontinuation and hospitalization. Overall, 49,062 patients were included; 5159 (10.5%) experienced hypoglycemia in the 6 months following basal insulin initiation. In the first 12 months, 68.1% of patients in the with hypoglycemia cohort discontinued basal insulin versus 53.9% in the without hypoglycemia cohort (p < .0001); more patients in the with hypoglycemia cohort had at least one hospitalization in the first year of follow-up (50.1% vs. 14.6%; p < .0001). Patients with hypoglycemia soon after initiating basal insulin are at greater risk of discontinuation of their basal insulin therapy and hospitalization versus those who did not have hypoglycemic events within the first 6 months of basal insulin initiation. A limitation of this study is that it was a retrospective analysis of EMR data and the study may not be representative of all US patients with T2D on basal insulin and it cannot be assumed that every hypoglycemic event was recorded.

Antioxidants Supplementation in Elderly Cardiovascular Patients

PubMed Central

Vila, Susana; Azzato, F.; Milei, José

2013-01-01

Supplementation with antioxidants and its benefit-risk relationship have been largely discussed in the elderly population. We evaluated whether antioxidants supplementation improved the biochemical profile associated with oxidative metabolism in elderly cardiovascular patients. Patients (n = 112) received daily supplementation with α-TP 400 mg, beta-carotene 40 mg, and vitamin C 1000 mg for 2 months (treatment). Plasma concentrations of alpha-tocopherol (α-TP), β-carotene (βC), ubiquinol-10 (QH-10), glutathione, and thiobarbituric acid reactive substances (TBARS) were determined before and after treatment. Response to treatment was dependent on pretreatment α-TP and βC levels. Increase in α-TP and βC levels was observed only in patients with basal levels <18 μM for α-TP (P < 0.01) and <0.30 μM for βC (P < 0.02). Ubiquinol-10, glutathione, and TBARS were unaffected by treatment: QH-10 (+57%, F 1,110 = 3.611, P < 0.06, and N.S.), glutathione (+21%, F 1,110 = 2.92, P < 0.09, and N.S.), and TBARS (−29%, F 1,110 = 2.26, P < 0.14, and N.S.). Treatment reduced oxidative metabolism: 5.3% versus 14.6% basal value (F 1,110 = 9.21, P < 0.0003). Basal TBARS/α-TP ratio was higher in smokers compared to nonsmokers: 0.11 ± 0.02 versus 0.06 ± 0.01 (F 32,80 = 1.63, P < 0.04). Response to antioxidant supplementation was dependent on basal plasma levels of α-TP and βC. Smoking status was strongly associated with atherosclerotic cardiovascular disease and high TBARS/α-TP ratio (lipid peroxidation). PMID:24489984

Vocal learning, prosody, and basal ganglia: don't underestimate their complexity.

PubMed

Ravignani, Andrea; Martins, Mauricio; Fitch, W Tecumseh

2014-12-01

Ackermann et al.'s arguments in the target article need sharpening and rethinking at both mechanistic and evolutionary levels. First, the authors' evolutionary arguments are inconsistent with recent evidence concerning nonhuman animal rhythmic abilities. Second, prosodic intonation conveys much more complex linguistic information than mere emotional expression. Finally, human adults' basal ganglia have a considerably wider role in speech modulation than Ackermann et al. surmise.

Costs of reducing sapling basal area in thinned cherry-maple stands in West Virginia

Treesearch

Gary W. Miller

1984-01-01

Unmanaged 60-year-old cherry-maple stands in West Virginia were thinned to three levels of stocking according to the Allegheny hardwoods stocking guide. After the merchantable timber was removed, the basal area in saplings was reduced to less than 10 ft² per acre (2.3 m²/ha), as the guide recommends for stands with dense understories. A detailed time...

Individual-tree basal area growth, survival, and total height models for upland hardwoods in the Boston Mountains of Arkansa

Treesearch

Paul A. Murphy; David L. Graney

1988-01-01

Models were developed for individual-tree basal area growth, survival, and total heights for different species of upland hardwoods in the Boston Mountains of north Arkansas. Data used were from 87 permanent plots located in an array of different sites and stand ages; the plots were thinned to different stocking levels and included unthinned controls. To test these...

Total and free iodothyronine changes in response to transport of Equidae (Equus asinus and Equus caballus).

PubMed

Fazio, Esterina; Medica, Pietro; Cravana, Cristina; Ferlazzo, Adriana

2017-03-31

In this study the effects of short distance road transport on total and free iodothyronine changes in 12 stallions (Equus asinus and Equus caballus) were evaluated. Donkeys (n = 6) and horses (n = 6) were transported for a distance of 50 km. Blood samples were collected 1 week before transport in basal conditions, 1 week later immediately before loading, and after transport and unloading. After transport, donkeys showed significant increases in circulating T4 (P≤0.01), fT3 (P≤0.001), and fT4 (P≤0.01) levels; while horses had significant increases in circulating T3, fT3 and fT4 (P≤0.01) levels. Compared to donkeys' values, horses showed lower T4 values in basal condition, before and after transport (P≤0.001); higher fT3 values in basal condition and before (P≤0.001), and lower values (P≤0.001) after transport; higher fT4 values (P≤0.001) in basal condition. The results indicate that short road transport of donkeys and horses induces the activation of the thyroid gland, with the same release of fT3 and fT4 iodothyronines, but with different preferential release of T3 in horses and T4 in donkeys after transport.

Evidence for basal distortion-product otoacoustic emission components.

PubMed

Martin, Glen K; Stagner, Barden B; Lonsbury-Martin, Brenda L

2010-05-01

Distortion-product otoacoustic emissions (DPOAEs) were measured with traditional DP-grams and level/phase (L/P) maps in rabbits with either normal cochlear function or unique sound-induced cochlear losses that were characterized as either low-frequency or notched configurations. To demonstrate that emission generators distributed basal to the f(2) primary-tone contribute, in general, to DPOAE levels and phases, a high-frequency interference tone (IT) was presented at 1/3 of an octave (oct) above the f(2) primary-tone, and DPOAEs were re-measured as "augmented" DP-grams (ADP-grams) and L/P maps. The vector difference between the control and augmented functions was then computed to derive residual DP-grams (RDP-grams) and L/P maps. The resulting RDP-grams and L/P maps, which described the DPOAEs removed by the IT, supported the notion that basal DPOAE components routinely contribute to the generation of standard measures of DPOAEs. Separate experiments demonstrated that these components could not be attributed to the effects of the 1/3-oct IT on f(2), or DPOAEs generated by the addition of a third interfering tone. These basal components can "fill in" the lesion estimated by the commonly employed DP-gram. Thus, ADP-grams more accurately reveal the pattern of cochlear damage and may eventually lead to an improved DP-gram procedure.

Activation of the JAK-STAT Signaling Pathway after In Vitro Stimulation with IFNß in Multiple Sclerosis Patients According to the Therapeutic Response to IFNß

PubMed Central

Hurtado-Guerrero, Isaac; Pinto-Medel, Maria Jesús; Urbaneja, Patricia; Rodriguez- Bada, Jose Luis; León, Antonio; Guerrero, Miguel; Fernández, Óscar

2017-01-01

Interferon beta (IFNß) is a common treatment used for multiple sclerosis (MS) which acts through the activation of the JAK-STAT pathway. However, this therapy is not always effective and currently there are no reliable biomarkers to predict therapeutic response. We postulate that the heterogeneity in the response to IFNß therapy could be related to differential activation patterns of the JAK-STAT signaling pathway. Our aim was to evaluate the basal levels and the short term activation of this pathway after IFNß stimulation in untreated and IFNß treated patients, as well as according to therapeutic response. Therefore, cell surface levels of IFNAR subunits (IFNAR1 and IFNAR2) and the activated forms of STAT1 and STAT2 were assessed in peripheral blood mononuclear cells from MS patients by flow cytometry. Basal levels of each of the markers strongly correlated with the expression of the others in untreated patients, but many of these correlations lost significance in treated patients and after short term activation with IFNß. Patients who had undergone IFNß treatment showed higher basal levels of IFNAR1 and pSTAT1, but a reduced response to in vitro exposure to IFNß. Conversely, untreated patients, with lower basal levels, showed a greater ability of short term activation of this pathway. Monocytes from responder patients had lower IFNAR1 levels (p = 0.039) and higher IFNAR2 levels (p = 0.035) than non-responders just after IFNß stimulation. A cluster analysis showed that levels of IFNAR1, IFNAR2 and pSTAT1-2 in monocytes grouped 13 out of 19 responder patients with a similar expression pattern, showing an association of this pattern with the phenotype of good response to IFNß (p = 0.013). Our findings suggest that an activation pattern of the IFNß signaling pathway in monocytes could be associated with a clinical phenotype of good response to IFNß treatment and that a differential modulation of the IFNAR subunits in monocytes could be related with treatment effectiveness. PMID:28103257

ΔNp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signaling

PubMed Central

Chakrabarti, Rumela; Wei, Yong; Hwang, Julie; Hang, Xiang; Blanco, Mario Andres; Choudhury, Abrar; Tiede, Benjamin; Romano, Rose-Anne; DeCoste, Christina; Mercatali, Laura; Ibrahim, Toni; Amadori, Dino; Kannan, Nagarajan; Eaves, Connie J; Sinha, Satrajit; Kang, Yibin

2014-01-01

Emerging evidence suggests that cancer is populated and maintained by tumor initiating cells (TICs) with stem-like properties similar to that of adult tissue stem cells. Despite recent advances, the molecular regulatory mechanisms that may be shared between normal and malignant stem cells remain poorly understood. Here we show that the ΔNp63 isoform of the Trp63 transcription factor promotes normal mammary stem cell (MaSC) activity by increasing the expression of the Wnt receptor Fzd7, thereby enhancing Wnt signaling. Importantly, Fzd7-dependent enhancement of Wnt signaling by ΔNp63 also governs tumor initiating activity of the basal subtype of breast cancer. These findings establish ΔNp63 as a key regulator of stem cells in both normal and malignant mammary tissues and provide direct evidence that breast cancer TICs and normal MaSCs share common regulatory mechanisms. PMID:25241036

Na+/K+-ATPase resistance and cardenolide sequestration: basal adaptations to host plant toxins in the milkweed bugs (Hemiptera: Lygaeidae: Lygaeinae)

PubMed Central

Bramer, Christiane; Dobler, Susanne; Deckert, Jürgen; Stemmer, Michael; Petschenka, Georg

2015-01-01

Despite sequestration of toxins being a common coevolutionary response to plant defence in phytophagous insects, the macroevolution of the traits involved is largely unaddressed. Using a phylogenetic approach comprising species from four continents, we analysed the ability to sequester toxic cardenolides in the hemipteran subfamily Lygaeinae, which is widely associated with cardenolide-producing Apocynaceae. In addition, we analysed cardenolide resistance of their Na+/K+-ATPases, the molecular target of cardenolides. Our data indicate that cardenolide sequestration and cardenolide-resistant Na+/K+-ATPase are basal adaptations in the Lygaeinae. In two species that shifted to non-apocynaceous hosts, the ability to sequester was secondarily reduced, yet Na+/K+-ATPase resistance was maintained. We suggest that both traits evolved together and represent major coevolutionary adaptations responsible for the evolutionary success of lygaeine bugs. Moreover, specialization on cardenolides was not an evolutionary dead end, but enabled this insect lineage to host shift to cardenolide-producing plants from distantly related families. PMID:25808891

Pineal peptides restore the age-related disturbances in hormonal functions of the pineal gland and the pancreas.

PubMed

Goncharova, N D; Vengerin, A A; Khavinson, V Kh; Lapin, B A

2005-01-01

The purpose of this research was to study age-related changes in functioning of pineal and pancreatic glands of non-human primates, rhesus monkeys, and to elucidate the possibility of their corrections with the help of epitalon, a synthetic analogue of the pharmacopoeia drug epithalamin. In old (20-27 years) animals, the basal plasma levels of glucose and insulin were found to be higher, while the night melatonin level was lower in comparison with (6-8 years) young animals. After the glucose administration to old monkeys, a larger area under the curve of the plasma glucose response, a reduced glucose 'disappearance' rate, and a reduced insulin peak (5 min after the glucose administration) were observed in comparison with young animals in similar experiments. The epitalon administration to old monkeys caused the decrease in the basal levels of glucose and insulin and the increase in the basal night melatonin level. Additionally, in the case of old monkeys, epitalon decreased the area under the plasma glucose response curve, markedly increased the glucose 'disappearance' rate and normalized the plasma insulin dynamics in response to glucose administration. Yet, it has not affected the hormonal and metabolic changes in young animals. Thus, epitalon is a promising factor for restoring the age-related endocrine dysfunctions of primates.

Potential for amelioration of aflatoxin B1-induced immunotoxic effects in progeny of White Leghorn breeder hens co-exposed to vitamin E.

PubMed

Khan, Wajid Arshad; Khan, Muhammad Zargham; Khan, Ahrar; Ul Hassan, Zahoor; Saleemi, Muhammad Kashif

2014-01-01

This study was designed to evaluate the protective activity of Vitamin E (Vit E) on the immunotoxic effects induced by aflatoxin B1 (AFB1) in the progeny of breeder hens. For this purpose, 192 White Leghorn (WL) layer breeder hens were divided into 12 groups (A-L) and then fed test diets for either 1, 2 or 3 weeks. Group A was kept on basal feed (2900 Kcal/kg metabolizable energy) and served as control, while group B was offered a feed supplemented with Vit E at 100 mg/Kg. Groups C-G were offered feed containing 0.1, 0.5, 2.5, 5.0, and 10.0 mg/Kg AFB1, respectively, whereas groups H-L were offered the same dietary levels of AFB1 along with 100 mg/Kg Vit E supplementation. Hatching eggs were shifted to an incubator on a weekly basis to get progeny chicks. Hatched chicks in each group were maintained on basal ration and then subjected to different immunological assays. Lymphoproliferative responses (against PHA-P), antibody titers (against SRBC), oxidative damage to RBC, as well as phagocytic and nitrite production potential of the peritoneal macrophages from the chicks, were all adversely impacted by hen exposure to the higher doses of AFB1 or by increased intake (time) by the hens at a given dose of the toxin. No consistent ameliorative effects from Vit E were noted in these studies, i.e. effects seen against lower AFB1 doses were no longer apparent with the highest doses of AFB1. As such, for now it can be concluded that, with this particular single dose level of Vit E, AFB1-associated immunotoxic effects in progeny chicks can potentially be mitigated by dietary intake of Vit E by their hen dams. However, this is clearly an outcome that is driven by the level of the mycotoxin present in the feed. Future studies need to examine what impact higher Vit E doses than those employed herein might have in these ameliorative outcomes.

Regulation of anti-apoptotic signaling by Kruppel-like factors 4 and 5 mediates lapatinib resistance in breast cancer

PubMed Central

Farrugia, M K; Sharma, S B; Lin, C-C; McLaughlin, S L; Vanderbilt, D B; Ammer, A G; Salkeni, M A; Stoilov, P; Agazie, Y M; Creighton, C J; Ruppert, J M

2015-01-01

The Kruppel-like transcription factors (KLFs) 4 and 5 (KLF4/5) are coexpressed in mouse embryonic stem cells, where they function redundantly to maintain pluripotency. In mammary carcinoma, KLF4/5 can each impact the malignant phenotype, but potential linkages to drug resistance remain unclear. In primary human breast cancers, we observed a positive correlation between KLF4/5 transcript abundance, particularly in the human epidermal growth factor receptor 2 (HER2)-enriched subtype. Furthermore, KLF4/5 protein was rapidly upregulated in human breast cancer cells following treatment with the HER2/epidermal growth factor receptor inhibitor, lapatinib. In addition, we observed a positive correlation between these factors in the primary tumors of genetically engineered mouse models (GEMMs). In particular, the levels of both factors were enriched in the basal-like tumors of the C3(1) TAg (SV40 large T antigen transgenic mice under control of the C3(1)/prostatein promoter) GEMM. Using tumor cells derived from this model as well as human breast cancer cells, suppression of KLF4 and/or KLF5 sensitized HER2-overexpressing cells to lapatinib. Indicating cooperativity, greater effects were observed when both genes were depleted. KLF4/5-deficient cells had reduced basal mRNA and protein levels of the anti-apoptotic factors myeloid cell leukemia 1 (MCL1) and B-cell lymphoma-extra large (BCL-XL). Moreover, MCL1 was upregulated by lapatinib in a KLF4/5-dependent manner, and enforced expression of MCL1 in KLF4/5-deficient cells restored drug resistance. In addition, combined suppression of KLF4/5 in cultured tumor cells additively inhibited anchorage-independent growth, resistance to anoikis and tumor formation in immunocompromised mice. Consistent with their cooperative role in drug resistance and other malignant properties, KLF4/5 levels selectively stratified human HER2-enriched breast cancer by distant metastasis-free survival. These results identify KLF4 and KLF5 as cooperating protumorigenic factors and critical participants in resistance to lapatinib, furthering the rationale for combining anti-MCL1/BCL-XL inhibitors with conventional HER2-targeted therapies. PMID:25789974

The insulinotropic potency of fatty acids is influenced profoundly by their chain length and degree of saturation.

PubMed Central

Stein, D T; Stevenson, B E; Chester, M W; Basit, M; Daniels, M B; Turley, S D; McGarry, J D

1997-01-01

Lowering of the elevated plasma FFA concentration in 18- 24-h fasted rats with nicotinic acid (NA) caused complete ablation of subsequent glucose-stimulated insulin secretion (GSIS). Although the effect of NA was reversed when the fasting level of total FFA was maintained by coinfusion of soybean oil or lard oil (plus heparin), the more saturated animal fat proved to be far more potent in enhancing GSIS. We therefore examined the influence of individual fatty acids on insulin secretion in the perfused rat pancreas. When present in the perfusion fluid at 0.5 mM (in the context of 1% albumin), the fold stimulation of insulin release from the fasted pancreas in response to 12.5 mM glucose was as follows: octanoate (C8:0), 3.4; linoleate (C18:2 cis/cis), 5.3; oleate (C18:1 cis), 9.4; palmitate (C16:0), 16. 2; and stearate (C18:0), 21.0. The equivalent value for palmitoleate (C16:1 cis) was 3.1. A cis--> trans switch of the double bond in the C16:1 and C18:1 fatty acids had only a modest, if any, impact on their potency. A similar profile emerged with regard to basal insulin secretion (3 mM glucose). When a subset of these fatty acids was tested in pancreases from fed animals, the same rank order of effectiveness at both basal and stimulatory levels of glucose was seen. The findings reaffirm the essentiality of an elevated plasma FFA concentration for GSIS in the fasted rat. They also show, however, that the insulinotropic effect of individual fatty acids spans a remarkably broad range, increasing and decreasing dramatically with chain length and degree of unsaturation, respectively. Thus, for any given level of glucose, insulin secretion will be influenced greatly not only by the combined concentration of all circulating (unbound) FFA, but also by the makeup of this FFA pool. Both factors will likely be important considerations in understanding the complex interplay between the nature of dietary fat and whole body insulin, glucose, and lipid dynamics. PMID:9218517

Angiotensin II Evokes Angiogenic Signals within Skeletal Muscle through Co-ordinated Effects on Skeletal Myocytes and Endothelial Cells

PubMed Central

Gorman, Jennifer L.; Liu, Sammy T. K.; Slopack, Dara; Shariati, Khashayar; Hasanee, Adam; Olenich, Sara; Olfert, I. Mark; Haas, Tara L.

2014-01-01

Skeletal muscle overload induces the expression of angiogenic factors such as vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-2, leading to new capillary growth. We found that the overload-induced increase in angiogenesis, as well as increases in VEGF, MMP-2 and MT1-MMP transcripts were abrogated in muscle VEGF KO mice, highlighting the critical role of myocyte-derived VEGF in controlling this process. The upstream mediators that contribute to overload-induced expression of VEGF have yet to be ascertained. We found that muscle overload increased angiotensinogen expression, a precursor of angiotensin (Ang) II, and that Ang II signaling played an important role in basal VEGF production in C2C12 cells. Furthermore, matrix-bound VEGF released from myoblasts induced the activation of endothelial cells, as evidenced by elevated endothelial cell phospho-p38 levels. We also found that exogenous Ang II elevates VEGF expression, as well as MMP-2 transcript levels in C2C12 myotubes. Interestingly, these responses also were observed in skeletal muscle endothelial cells in response to Ang II treatment, indicating that these cells also can respond directly to the stimulus. The involvement of Ang II in muscle overload-induced angiogenesis was assessed. We found that blockade of AT1R-dependent Ang II signaling using losartan did not attenuate capillary growth. Surprisingly, increased levels of VEGF protein were detected in overloaded muscle from losartan-treated rats. Similarly, we observed elevated VEGF production in cultured endothelial cells treated with losartan alone or in combination with Ang II. These studies conclusively establish the requirement for muscle derived VEGF in overload-induced angiogenesis and highlight a role for Ang II in basal VEGF production in skeletal muscle. However, while Ang II signaling is activated following overload and plays a role in muscle VEGF production, inhibition of this pathway is not sufficient to halt overload-induced angiogenesis, indicating that AT1-independent signals maintain VEGF production in losartan-treated muscle. PMID:24416421

Adult cystic fibrosis: postprandial response of gut regulatory peptides.

PubMed

Allen, J M; Penketh, A R; Adrian, T E; Lee, Y C; Sarson, D L; Hodson, M E; Batten, J C; Bloom, S R

1983-12-01

Responses of 11 gastrointestinal regulatory peptides to a standard test meal were assessed in 10 adult patients with cystic fibrosis. The basal plasma neurotensin was significantly elevated in patients with cystic fibrosis, being 31.5 +/- 6.1 pmol/L compared with a control value of 10.3 +/- 1.5 pmol/L (p less than 0.005). Plasma neurotensin remained elevated throughout the test period. Basal plasma enteroglucagon was similarly elevated, the patients with fibrocystic disease having levels of 51.3 +/- 4.6 pmol/L compared to controls with levels of 33.2 +/- 6.7 pmol/L (p less than 0.02). There was, however, no significant difference in postprandial levels of plasma enteroglucagon. Postprandial motilin was significantly elevated in the patients with cystic fibrosis; this elevation is in contrast with previous findings in children. Release of gastric inhibitory polypeptide was impaired, while release of cholecystokinin showed no significant difference in control values, although there was a tendency for delay. There was no significant postprandial rise of pancreatic polypeptide in the patients, whose levels were grossly lower than controls. Insulin showed a delayed response. No significant differences were observed between patients and controls in levels of gastrin, pancreatic glucagon, somatostatin, or vasoactive intestinal peptide. The elevation of plasma neurotensin and enteroglucagon in the basal state may reflect an adaptive response and may be part of the improved digestive function in adults compared with children with fibrocystic disease.

Reduced steroidogenesis in patients with PCDH19-female limited epilepsy.

PubMed

Trivisano, Marina; Lucchi, Chiara; Rustichelli, Cecilia; Terracciano, Alessandra; Cusmai, Raffaella; Ubertini, Grazia Maria; Giannone, Germana; Bertini, Enrico Silvio; Vigevano, Federico; Gecz, Jozef; Biagini, Giuseppe; Specchio, Nicola

2017-06-01

Patients affected by protocadherin 19 (PCDH19)-female limited epilepsy (PCDH19-FE) present a remarkable reduction in allopregnanolone blood levels. However, no information is available on other neuroactive steroids and the steroidogenic response to hormonal stimulation. For this reason, we evaluated allopregnanolone, pregnanolone, and pregnenolone sulfate by liquid chromatographic procedures coupled with electrospray tandem mass spectrometry in 12 unrelated patients and 15 age-matched controls. We also tested cortisol, estradiol, progesterone, and 17OH-progesterone using standard immunoassays. Apart from estradiol and progesterone, all the considered hormones were evaluated in basal condition and after stimulation with adrenocorticotropic hormone (ACTH). A generalized decrease in blood levels of almost all measured neuroactive steroids was found. When considering sexual development, cortisol and pregnenolone sulfate basal levels were significantly reduced in postpubertal girls affected by PCDH19-FE. Of interest, ACTH administration did not recover pregnenolone sulfate serum levels but restored cortisol to control levels. In prepubertal girls with PCDH19-FE, by challenging adrenal function with ACTH we disclosed defects in the production of cortisol, pregnenolone sulfate, and 17OH-progesterone, which were not apparent in basal condition. These findings point to multiple defects in peripheral steroidogenesis associated with and potentially relevant to PCDH19-FE. Some of these defects could be addressed by stimulating adrenocortical activity. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Influence of dietary protein level on the broiler chicken's response to methionine and betaine supplements.

PubMed

Garcia Neto, M; Pesti, G M; Bakalli, R I

2000-10-01

Two experiments were conducted to compare broiler chicken responses to methionine and betaine supplements when fed diets with low protein and relatively high metabolizable energy levels (17%, 3.3 kcal/g) or moderate protein and lower metabolizable energy levels (24%, 3.0 kcal/g), resulting in different levels of carcass fat. In Experiment 1, the basal diets were formulated with corn, soybean meal, poultry by-product meal, and poultry oil. In Experiment 2, glucose monohydrate was also added, so that identical amino acid profiles could be maintained in the 17 and 24% protein diets. On average, feeding the 17 vs. 24% protein diet decreased 21-d body weight gain by 20%, increased feed conversion ratio (FCR) by 13%, and increased abdominal fat pad weight by 104%. Methionine and betaine supplements improved the performance of chicks fed the 24% protein diet in both experiments, as indicated by body weight gain and FCR. Only supplementary methionine increased performance of chicks fed 17% protein diets, and then only in Experiment 2. Neither methionine nor betaine decreased abdominal fat pad size in either experiment. Methionine supplementation decreased relative liver size and increased breast muscle protein. Both methionine and betaine increased sample feather weight, but when expressed as a percentage of body weight, no significant differences were detected. It is concluded that increasing carcass fat by manipulating percentage dietary protein level or amino acid balance does not influence betaine's activity as a lipotropic agent.

Emerging Role of Corticosteroid-Binding Globulin in Glucocorticoid-Driven Metabolic Disorders.

PubMed

Moisan, Marie-Pierre; Castanon, Nathalie

2016-01-01

Glucocorticoid hormones (GCs) are critical for survival since they ensure the energy supply necessary to the body in an ever challenging environment. GCs are known to act on appetite, glucose metabolism, fatty acid metabolism, and storage. However, to be beneficial to the body, GC levels should be maintained in an optimal window of concentrations. Not surprisingly, conditions of GC excess or deficiency, e.g., Cushing's syndrome or Addison's disease, are associated with severe alterations of energy metabolism. Corticosteroid-binding globulin (CBG), through its high specific affinity for GCs, plays a critical role in regulating plasma GC levels and their access to target cells. Genetic studies in various species including humans have revealed that CBG is the major factor influencing interindividual genetic variability of plasma GC levels, both in basal and stress conditions. Some, but not all, of these genetic studies have also provided data linking CBG levels to body composition and insulin levels. The examination of CBG-deficient mice submitted to hyperlipidic diets unveiled specific roles for CBG in lipid storage and metabolism. An influence of CBG on appetite has not been reported but remains to be more finely analyzed. Finally, only male mice have been examined under high-fat diet, while obesity is affecting women even more than men. Overall, a role of CBG in GC-driven metabolic disorders is emerging in recent studies. Although subtle, the influence of CBG in these diseases could open the way to new therapeutic interventions since CBG is easily accessible in the blood.

Computational modelling of locomotor muscle moment arms in the basal dinosaur Lesothosaurus diagnosticus: assessing convergence between birds and basal ornithischians

PubMed Central

Bates, Karl T; Maidment, Susannah C R; Allen, Vivian; Barrett, Paul M

2012-01-01

Ornithischia (the ‘bird-hipped’ dinosaurs) encompasses bipedal, facultative quadrupedal and quadrupedal taxa. Primitive ornithischians were small bipeds, but large body size and obligate quadrupedality evolved independently in all major ornithischian lineages. Numerous pelvic and hind limb features distinguish ornithischians from the majority of other non-avian dinosaurs. However, some of these features, notably a retroverted pubis and elongate iliac preacetabular process, appeared convergently in maniraptoran theropods, and were inherited by their avian descendants. During maniraptoran/avian evolution these pelvic modifications led to significant changes in the functions of associated muscles, involving alterations to the moment arms and the activation patterns of pelvic musculature. However, the functions of these features in ornithischians and their influence on locomotion have not been tested and remain poorly understood. Here, we provide quantitative tests of bipedal ornithischian muscle function using computational modelling to estimate 3D hind limb moment arms for the most complete basal ornithischian, Lesothosaurus diagnosticus. This approach enables sensitivity analyses to be carried out to explore the effects of uncertainties in muscle reconstructions of extinct taxa, and allows direct comparisons to be made with similarly constructed models of other bipedal dinosaurs. This analysis supports some previously proposed qualitative inferences of muscle function in basal ornithischians. However, more importantly, this work highlights ambiguities in the roles of certain muscles, notably those inserting close to the hip joint. Comparative analysis reveals that moment arm polarities and magnitudes in Lesothosaurus, basal tetanuran theropods and the extant ostrich are generally similar. However, several key differences are identified, most significantly in comparisons between the moment arms of muscles associated with convergent osteological features in ornithischians and birds. Craniad migration of the iliofemoralis group muscles in birds correlates with increased leverage and use of medial femoral rotation to counter stance phase adduction moments at the hip. In Lesothosaurus the iliofemoralis group maintains significantly higher moment arms for abduction, consistent with the hip abduction mode of lateral limb support hypothesized for basal dinosaurs. Sensitivity analysis highlights ambiguity in the role of musculature associated with the retroverted pubis (puboischiofemoralis externus group) in ornithischians. However, it seems likely that this musculature may have predominantly functioned similarly to homologous muscles in extant birds, activating during the swing phase to adduct the lower limb through lateral rotation of the femur. Overall the results suggest that locomotor muscle leverage in Lesothosaurus (and by inference basal ornithischians in general) was more similar to that of other non-avian dinosaurs than the ostrich, representing what was probably the basal dinosaur condition. This work thereby contradicts previous hypotheses of ornithischian–bird functional convergence. PMID:22211275

Computational modelling of locomotor muscle moment arms in the basal dinosaur Lesothosaurus diagnosticus: assessing convergence between birds and basal ornithischians.

PubMed

Bates, Karl T; Maidment, Susannah C R; Allen, Vivian; Barrett, Paul M

2012-03-01

Ornithischia (the 'bird-hipped' dinosaurs) encompasses bipedal, facultative quadrupedal and quadrupedal taxa. Primitive ornithischians were small bipeds, but large body size and obligate quadrupedality evolved independently in all major ornithischian lineages. Numerous pelvic and hind limb features distinguish ornithischians from the majority of other non-avian dinosaurs. However, some of these features, notably a retroverted pubis and elongate iliac preacetabular process, appeared convergently in maniraptoran theropods, and were inherited by their avian descendants. During maniraptoran/avian evolution these pelvic modifications led to significant changes in the functions of associated muscles, involving alterations to the moment arms and the activation patterns of pelvic musculature. However, the functions of these features in ornithischians and their influence on locomotion have not been tested and remain poorly understood. Here, we provide quantitative tests of bipedal ornithischian muscle function using computational modelling to estimate 3D hind limb moment arms for the most complete basal ornithischian, Lesothosaurus diagnosticus. This approach enables sensitivity analyses to be carried out to explore the effects of uncertainties in muscle reconstructions of extinct taxa, and allows direct comparisons to be made with similarly constructed models of other bipedal dinosaurs. This analysis supports some previously proposed qualitative inferences of muscle function in basal ornithischians. However, more importantly, this work highlights ambiguities in the roles of certain muscles, notably those inserting close to the hip joint. Comparative analysis reveals that moment arm polarities and magnitudes in Lesothosaurus, basal tetanuran theropods and the extant ostrich are generally similar. However, several key differences are identified, most significantly in comparisons between the moment arms of muscles associated with convergent osteological features in ornithischians and birds. Craniad migration of the iliofemoralis group muscles in birds correlates with increased leverage and use of medial femoral rotation to counter stance phase adduction moments at the hip. In Lesothosaurus the iliofemoralis group maintains significantly higher moment arms for abduction, consistent with the hip abduction mode of lateral limb support hypothesized for basal dinosaurs. Sensitivity analysis highlights ambiguity in the role of musculature associated with the retroverted pubis (puboischiofemoralis externus group) in ornithischians. However, it seems likely that this musculature may have predominantly functioned similarly to homologous muscles in extant birds, activating during the swing phase to adduct the lower limb through lateral rotation of the femur. Overall the results suggest that locomotor muscle leverage in Lesothosaurus (and by inference basal ornithischians in general) was more similar to that of other non-avian dinosaurs than the ostrich, representing what was probably the basal dinosaur condition. This work thereby contradicts previous hypotheses of ornithischian-bird functional convergence. © 2012 The Authors. Journal of Anatomy © 2012 Anatomical Society.

Advanced technique for long term culture of epithelia in a continuous luminal-basal medium gradient.

PubMed

Schumacher, Karl; Strehl, Raimund; de, Vries Uwe; Minuth, Will W

2002-02-01

The majority of epithelia in our organism perform barrier functions on being exposed to different fluids at the luminal and basal sides. To simulate this natural situation under in vitro conditions for biomaterial testing and tissue engineering the epithelia have to withstand mechanical and fluid stress over a prolonged period of time. Leakage, edge damage and pressure differences in the culture system have to be avoided so that the epithelial barrier function is maintained. Besides, the environmental influences on important cell biological features such as, sealing or transport functions, have to remain upregulated and a loss of characteristics by dedifferentiation is prevented. Our aim is to expose embryonic renal collecting duct (CD) epithelia as model tissue for 14 days to fluid gradients and to monitor the development of tissue-specific features. For these experiments, cultured embryonic epithelia are placed in tissue carriers and in gradient containers, where different media are superfused at the luminal and basal sides. Epithelia growing on the tissue carriers act as a physiological barrier during the whole culture period. To avoid mechanical damage of the tissue and to suppress fluid pressure differences between the luminal and basal compartments improved transport of the medium and an elimination of unilaterally accumulated gas bubbles in the gradient container compartments by newly developed gas expander modules is introduced. By the application of these tools the yield of embryonic renal collecting duct epithelia with intact barrier function on a fragile natural support material could be increased significantly as compared to earlier experiments. Epithelia treated with a luminal NaCl load ranging from 3 to 24 mmol l were analyzed by immunohistochemical methods to determine the degree of differentiation. The tissue showed an upregulation of individual CD cell features as compared to embryonic epithelia in the neonatal kidney.

Effects of nonfiction guided interactive read-alouds and think-alouds on fourth grader's depth of content area science vocabulary knowledge and comprehension

NASA Astrophysics Data System (ADS)

Hanna, Tania Tamara

Effects of nonfiction guided interactive read-alouds and think-alouds as a supplement to basal science textbooks on three vocabulary measures, definitions, examples, and characteristics, and one multiple-choice comprehension measure were assessed for 127 fourth graders over three time periods: pretest, posttest, and a 2-week delayed posttest. Two of three fourth-grade elementary science teachers implemented a series of 12 content-enhanced guided interactive scripted lessons. Two of these teachers implemented two treatments each. The first condition employed basal science textbooks as the text for guided interactive read-alouds and think-alouds while the second treatment employed basal science textbooks in conjunction with nonfiction text sets as the texts for guided interactive read-alouds and think-alouds. The third teacher, guided by traditional lesson plans, provided students with silent independent reading instruction using basal science textbooks. Multivariate analyses of variance and analyses of variance tests showed that mean scores for both treatment groups significantly improved on definitions and characteristics measures at posttest and either stabilized or slightly declined at delayed posttest. The treatment-plus group lost considerably on the examples posttest measure. The treatment group improved mean scores on the examples posttest measure, outperforming the treatment-plus group and the control group. Alternately, the control group significantly improved on the delayed posttest examples measure. Additionally, the two groups implementing guided interactive read-alouds and think-alouds performed better than the independent reading group on multiple-choice comprehension measures at posttest and sustained those gains 2 weeks later on delayed posttests. Findings maintain the incremental nature of vocabulary acquisition and development research and emphasize the roles of listening and speaking as critical features for integrating vocabulary into long-term memory.

In-pot evaluation of different composted and pelletized organic fertilizers on soil carbon dioxide efflux and basal respiration

NASA Astrophysics Data System (ADS)

Opsi, Francesca; Cavallo, Eugenio; Cocco, Stefania; Corti, Giuseppe

2013-04-01

Climate change is one of the most important environmental problems and it is closely related to concentration changes of greenhouse gases (GHG) in the atmosphere, mainly due to anthropogenic activities. As a consequence, measures have been taken to reduce GHG emissions, some of which are associated with agriculture, as well as to the enhancement of soil carbon storage. Modern intensive farming activities have also raised problems related to the safe disposal of large volume of animal waste, such as pig slurry, where the excessive land spreading can lead to water pollution and GHG evolution to the atmosphere. Composting is a great environmentally sustainable option for recycling agricultural by-products, and pelletisation is a promising technology to reduce the large volume of mature composted material in pelleted fertilizers, more suitable for long-distance transport. This study consisted of a pot-incubation experience carried out in a greenhouse of the National Research Council of Italy, under controlled conditions. The aim of the research was to investigate the effect of a composted swine solid fraction (CS, 13% w/w) and swine solid fraction blended with sawdust and composted (CSS, 9% w/w), both also as a result of pelletisation process (CSP, 12% w/w and CSSP, 8% w/w, respectively), on soil organic matter mineralization and basal respiration. Results were obtained by monitoring CO2 efflux, basal respiration and microbial biomass C on amended soil, freshly collected in a vineyard planted on a Typic Ustorthent, fine-loamy, mixed, calcareous, mesic. Samples, adjusted and maintained to about 50-60% of water holding capacity, were conditioned at 25±3 °C for 31 days of incubation. The CO2 fluxes showed a high production at the initial stage of incubation, where differences among treatments were well-rendered. CSSP produced the highest values, while CSS showed values as lower as about 45%. Intermediate values, and similar to those found in the soil sample used as control, were reported by CS and CSP treatments. The daily basal respiration rate confirmed what was previously observed, namely that microorganisms of CSSP showed an increased level of respiration followed by CS, while CSP and CSS treatments were characterized by a lower respiration activity. The addition of fertilizers caused an inhibition of microorganisms in the soil. The CSSP and CS samples showed the lowest values of microbial biomass C and the highest metabolic quotient levels, which were ascribed to stress conditions that led to a greater consumption of energy and therefore a high respiration activity. The higher mineralization rate of CSSP in the soil suggested that this material should not be tested under field scale conditions, while the protective role in term of degradation played by sawdust to organic matter could be better expressed in free form compared to pelletized one.

Optimal cutoff value of basal anti-mullerian hormone in iranian infertile women for prediction of ovarian hyper-stimulation syndrome and poor response to stimulation.

PubMed

Aghssa, Malek Mansour; Tarafdari, Azam Manshadi; Tehraninejad, Ensieh Shahrokh; Ezzati, Mohammad; Bagheri, Maryam; Panahi, Zahra; Mahdavi, Saeed; Abbasi, Mehrshad

2015-09-10

We intended to establish the threshold of Anti-Mullerian Hormone (AMH) for detection of Ovarian Hyper-Stimulation Syndrome (OHSS) and poor response to treatment in Iranian infertile women. Pre-stimulation menstrual cycle day-3 hormonal indices including basal AMH values were measured in 105 infertile women aged 32.5 ± 4.3 years. Patients underwent long GnRH agonist Controlled Ovarian Hyperstimulation (COH) in a referral infertility center (Tehran, Iran). The gonadotropin dose was determined based on the age and basal serum Follicular Stimulating Hormone (FSH) level. The IVF/ICSI cycles were followed and the clinical and sonographic data were recorded. Sixteen cases developed OHSS. The prevalence of PCOS was higher in subjects with OHSS [62.5 % (38.8-86.2) vs. 17 % (9.2-24.9)]. The patients with OHSS had higher ovarian follicular count [23.7 (3.2) vs. 9.1 (0.5); p < 0.05], collected oocytes [13.5 (1.9) vs. 6.9 (0.5); p < 0.05] and AMH level [7.9 (0.7) vs. 3.6 (0.3); p < 0.05]. Basal AMH level and oocyte yields (but not age, BMI, and PCOS) correlated with occurrence of OHSS; and only the AMH levels were associated with poor ovarian response (oocytes yield ≤ 4). The optimal cutoff value for the prediction of OHSS was 6.95 ng/ml (area under the receiver operating characteristics curve: 0.86; CI: 0.78-0.95; sensitivity: 75 %; specificity: 84 %; odds ratio for occurrence of OHSS: 9 and p < 0.001). The optimal cut point to discriminate poor response (oocytes ≤4) was 1.65 ng/ml ( AUC : 0.8; CI: 0.69-0.91; sensitivity: 89 % specificity : 71 %; and OR = 23.8 and P value <0.001). Iranian women with basal AMH level > 6.95 ng/ml are at high risk of developing OHSS and those with AMH level < 1.65 ng/ml are poor responders.

Follicle-stimulating hormone receptor-mediated uptake of sup 45 Ca sup 2+ by cultured rat Sertoli cells does not require activation of cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding proteins or adenylate cyclase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grasso, P.; Reichert, L.E. Jr.

1990-08-01

We have previously reported that FSH stimulates flux of 45Ca2+ into cultured Sertoli cells from immature rats via voltage-sensitive and voltage-independent calcium channels. In the present study, we show that this effect of FSH does not require cholera toxin (CT)- or pertussis toxin (PT)-sensitive guanine nucleotide binding (G) protein or activation of adenylate cyclase (AC). Significant stimulation of 45Ca2+ influx was observed within 1 min, and maximal response (3.2-fold over basal levels) was achieved within 2 min after exposure to FSH. FSH-stimulated elevations in cellular cAMP paralleled increases in 45Ca2+ uptake, suggesting a possible coupling of AC activation to 45Ca2+more » influx. (Bu)2cAMP, however, was not able to enhance 45Ca2+ uptake over basal levels at a final concentration of 1000 microM, although a concentration-related increase in androstenedione conversion to estradiol was evident. Exposure of Sertoli cells to CT (10 ng/ml) consistently stimulated basal levels of androstenedione conversion to estradiol but had no effect on basal levels of 45Ca2+ uptake. Similarly, CT had no effect on FSH-induced 45Ca2+ uptake, but potentiated FSH-stimulated estradiol synthesis. PT (10 ng/ml) augmented basal and FSH-stimulated estradiol secretion without affecting 45Ca2+ influx. The adenosine analog N6-phenylisopropyladenosine, which binds to Gi-coupled adenosine receptors on Sertoli cells, inhibited FSH-stimulated androgen conversion to estradiol in a dose-related (1-1000 nM) manner, but FSH-stimulated 45Ca2+ influx remained unchanged. Our results show that in contrast to FSH-stimulated estradiol synthesis, the flux of 45Ca2+ into Sertoli cells in response to FSH is not mediated either directly or indirectly by CT- or PT-sensitive G protein, nor does it require activation of AC. Our data further suggest that the FSH receptor itself may function as a calcium channel.« less

Dopamine D1 receptor activation maintains motor coordination and balance in rats.

PubMed

Avila-Luna, Alberto; Gálvez-Rosas, Arturo; Durand-Rivera, Alfredo; Ramos-Languren, Laura-Elisa; Ríos, Camilo; Arias-Montaño, José-Antonio; Bueno-Nava, Antonio

2018-02-01

Dopamine (DA) modulates motor coordination, and its depletion, as in Parkinson's disease, produces motor impairment. The basal ganglia, cerebellum and cerebral cortex are interconnected, have functional roles in motor coordination, and possess dopamine D 1 receptors (D 1 Rs), which are expressed at a particularly high density in the basal ganglia. In this study, we examined whether the activation of D 1 Rs modulates motor coordination and balance in the rat using a beam-walking test that has previously been used to detect motor coordination deficits. The systemic administration of the D 1 R agonist SKF-38393 at 2, 3, or 4 mg/kg did not alter the beam-walking scores, but the subsequent administration of the D 1 R antagonist SCH-23390 at 1 mg/kg did produce deficits in motor coordination, which were reversed by the full agonist SKF-82958. The co-administration of SKF-38393 and SCH-23390 did not alter the beam-walking scores compared with the control group, but significantly prevented the increase in beam-walking scores induced by SCH-23390. The effect of the D 1 R agonist to prevent and reverse the effect of the D 1 R antagonist in beam-walking scores is an indicator that the function of D 1 Rs is necessary to maintain motor coordination and balance in rats. Our results support that D 1 Rs mediate the SCH-23390-induced deficit in motor coordination.

GROα regulates human embryonic stem cell self-renewal or adoption of a neuronal fate

PubMed Central

Krtolica, Ana; Larocque, Nick; Genbacev, Olga; Ilic, Dusko; Coppe, Jean-Philippe; Patil, Christopher K.; Zdravkovic, Tamara; McMaster, Michael; Campisi, Judith; Fisher, Susan J.

2012-01-01

Previously we reported that feeders formed from human placental fibroblasts (hPFs) support derivation and long-term self-renewal of human embryonic stem cells (hESCs) under serum-free conditions. Here, we show, using antibody array and ELISA platforms, that hPFs secrete ~6-fold higher amounts of the CXC-type chemokine, GROα, than IMR 90, a human lung fibroblast line, which does not support hESC growth. Furthermore, immunocytochemistry and immunoblot approaches revealed that hESCs express CXCR, a GROα receptor. We used this information to develop defined culture medium for feeder-free propagation of hESCs in an undifferentiated state. Cells passaged as small aggregates and maintained in the GROα-containing medium had a normal karyotype, expressed pluripotency markers, and exhibited apical–basal polarity, i.e., had the defining features of pluripotent hESCs. They also differentiated into the three primary (embryonic) germ layers and formed teratomas in immunocompromised mice. hESCs cultured as single cells in the GROα-containing medium also had a normal karyotype, but they downregulated markers of pluripotency, lost apical–basal polarity, and expressed markers that are indicative of the early stages of neuronal differentiation—βIII tubulin, vimentin, radial glial protein, and nestin. These data support our hypothesis that establishing and maintaining cell polarity is essential for the long-term propagation of hESCs in an undifferentiated state and that disruption of cell–cell contacts can trigger adoption of a neuronal fate. PMID:21396766

Long-term Culture and Cloning of Primary Human Bronchial Basal Cells that Maintain Multipotent Differentiation Capacity and CFTR Channel Function.

PubMed

Peters-Hall, Jennifer Ruth; Coquelin, Melissa L; Torres, Michael J; LaRanger, Ryan; Alabi, Busola Ruth; Sho, Sei; Calva-Moreno, Jose Francisco; Thomas, Philip J; Shay, Jerry William

2018-05-03

While primary cystic fibrosis (CF) and non-CF human bronchial epithelial basal cells (HBECs) accurately represent in vivo phenotypes, one barrier to their wider use has been a limited ability to clone and expand cells in sufficient numbers to produce rare genotypes using genome editing tools. Recently, conditional reprogramming of cells (CRC) with a ROCK inhibitor and culture on an irradiated fibroblast feeder layer resulted in extension of the lifespan of HBECs, but differentiation capacity and CF transmembrane conductance regulator (CFTR) function decreased as a function of passage. This report details modifications to the standard HBEC CRC protocol (Mod CRC), including the use of bronchial epithelial growth medium instead of F-medium and 2% oxygen instead of 21% oxygen, that extend HBEC lifespan while preserving multipotent differentiation capacity and CFTR function. Critically, Mod CRC conditions support clonal growth of primary HBECs from a single cell and the resulting clonal HBEC population maintains multipotent differentiation capacity, including CFTR function, permitting gene editing of these cells. As a proof of concept, CRISPR/Cas9 genome editing and cloning was used to introduce insertions/deletions in CFTR exon 11. Mod CRC conditions overcome many barriers to the expanded use of HBECs for basic research and drug screens. Importantly, Mod CRC conditions support the creation of isogenic cell lines in which CFTR is mutant or wild-type in the same genetic background with no history of CF to enable determination of the primary defects of mutant CFTR.

The effects of extreme nutritional conditions on the neurochemistry of reward and addiction

NASA Astrophysics Data System (ADS)

Pothos, Emmanuel N.

2001-08-01

Weight loss is a frequent problem in space flights. We now claim that it may affect performance and drug-seeking behavior by altering midbrain neurochemistry. In food-deprived rats (20-30% underweight) basal extracellular dopamine levels in the nucleus accumbens decrease to 40-50% of normal and locomotion is depressed. However, amphetamine-induced dopamine release and locomotion are higher than in controls (1825% vs. 595% after a 25 μM d-amphetamine intraaccumbens infusion). The lower basal and the higher stimulated dopamine levels suggest that the neurotransmitter accumulates presynaptically in the accumbens of the underweight rats due to subnormal basal release. Psychostimulants are more rewarding for underweight subjects possibly because they release significantly more dopamine from elevated presynaptic stores into the accumbens. Consequently, weight loss can lead both to depression of performance and propensity to substance abuse. These effects should be considered when providing nutritional resources for space flights so that weight loss is limited.

Hormonal and metabolic effects of neuroglucopenia.

PubMed

Molina, P E; Eltayeb, K; Hourani, H; Okamura, K; Nanney, L B; Williams, P; Abumrad, N N

1993-06-18

We examined the role of central neuroglucopenia, induced by intracerebroventricular (i.c.v.) administration of 2-deoxyglucose (2-DG), on glucose and amino acid kinetics in conscious dogs. Group 1 received i.c.v. 2-DG at 2.5 mg.kg-1 x min-1 for 15 min. Group 2 received an equal intravenous (i.v.) amount of 2-DG. In the i.c.v. group, plasma glucose levels rose from 106 +/- 4 mg/dl to a peak of 204 +/- 12 mg/dl by 90 min. Blood lactate increased from 689 +/- 1 to 2,812 +/- 5 mumol/l and blood alanine not change from basal (256 +/- 41 mumol/l). The rate of hepatic glucose production, determined isotopically, was increased 2-fold over basal (P < 0.01). Significant increases (P < 0.001) over basal were also noted in plasma epinephrine, norepinephrine, insulin, glucagon and cortisol. Leucine rate of appearance (Ra) showed a 30% decrease from basal to 2.4 +/- 0.05 mumol.kg-1 x min-1 (P < 0.01). In group 2 plasma glucose levels were not altered but plasma cortisol and glucagon showed a modest transient increase above basal (P < 0.05). No significant changes were noted in amino acid kinetics. These findings suggest that periventricular neuroglucopenia, in the absence of peripheral glucose deprivation, is accompanied by hyperglycemia secondary to enhanced hepatic glucose production with decreased glucose utilization and by increased hepatic uptake of gluconeogenic precursors. These, however, were not accompanied by increased whole body proteolysis as was previously seen with generalized glucopenia resulting from insulin-induced hypoglycemia.

CRB2 in immature photoreceptors determines the superior-inferior symmetry of the developing retina to maintain retinal structure and function.

PubMed

Quinn, Peter M; Alves, C Henrique; Klooster, Jan; Wijnholds, Jan

2018-06-08

The mammalian apical-basal determinant Crumbs homolog-1 (CRB1) plays a crucial role in retinal structure and function by the maintenance of adherens junctions between photoreceptors and Müller glial cells. Patients with mutations in the CRB1 gene develop retinal dystrophies, including early-onset retinitis pigmentosa and Leber congenital amaurosis. Previously, we showed that Crb1 knockout mice developed a slow-progressing retinal phenotype at foci in the inferior retina, whiles specific ablation of Crb2 in immature photoreceptors lead to an early-onset phenotype throughout the retina. Here, we conditionally disrupted one or both alleles of Crb2 in immature photoreceptors, on a genetic background lacking Crb1, and studied the retinal dystrophies thereof. Our data showed that disruption of one allele of Crb2 in immature photoreceptors caused a substantial aggravation of the Crb1 phenotype in the entire inferior retina. The photoreceptor layer showed early-onset progressive thinning limited to the inferior retina while the superior retina maintained intact. Surprisingly, disruption of both alleles of Crb2 in immature photoreceptors further aggravated the phenotype. Throughout the retina, photoreceptor synapses were disrupted and photoreceptor nuclei intermingled with nuclei of the inner nuclear layer. In the superior retina, the ganglion cell layer appeared thicker due to ectopic nuclei of photoreceptors. In conclusion, the data suggest that CRB2 is required to maintain retinal progenitor and photoreceptor cell adhesion and prevent photoreceptor ingression into the immature inner retina. We hypothesise, from these animal models, that decreased levels of CRB2 in immature photoreceptors adjust retinitis pigmentosa due to loss of CRB1 into Leber congenital amaurosis phenotype.

SIRT1 directly regulates SOX2 to maintain self-renewal and multipotency in bone marrow-derived mesenchymal stem cells.

PubMed

Yoon, Dong Suk; Choi, Yoorim; Jang, Yeonsue; Lee, Moses; Choi, Woo Jin; Kim, Sung-Hwan; Lee, Jin Woo

2014-12-01

SOX2 is crucial for the maintenance of the self-renewal capacity and multipotency of mesenchymal stem cells (MSCs); however, the mechanism by which SOX2 is regulated remains unclear. Here, we report that RNA interference of sirtuin 1 (SIRT1) in human bone marrow (BM)-derived MSCs leads to a decrease of SOX2 protein, resulting in the deterioration of the self-renewal and differentiation capacities of BM-MSCs. Using immunoprecipitation, we demonstrated direct binding between SIRT1 and SOX2 in HeLa cells overexpressing SOX2. We further discovered that the RNA interference of SIRT1 induces the acetylation, nuclear export, and ubiquitination of SOX2, leading to proteasomal degradation in BM-MSCs. SOX2 suppression by trichostatin A (TSA), a known histone deacetylase inhibitor, was reverted by treatment with resveratrol (0.1 and 1 µM), a known activator of SIRT1 in BM-MSCs. Furthermore, 0.1 and 1 µM resveratrol reduced TSA-mediated acetylation and ubiquitination of SOX2 in BM-MSCs. SIRT1 activation by resveratrol enhanced the colony-forming ability and differentiation potential to osteogenic and adipogenic lineages in a dose-dependent manner. However, the enhancement of self-renewal and multipotency by resveratrol was significantly decreased to basal levels by RNA interference of SOX2. These results strongly suggest that the SIRT1-SOX2 axis plays an important role in maintaining the self-renewal capability and multipotency of BM-MSCs. In conclusion, our findings provide evidence for positive SOX2 regulation by post-translational modification in BM-MSCs through the inhibition of nuclear export and subsequent ubiquitination, and demonstrate that SIRT1-mediated deacetylation contributes to maintaining SOX2 protein in the nucleus. © 2014 AlphaMed Press.

A measurement error model for physical activity level as measured by a questionnaire with application to the 1999-2006 NHANES questionnaire.

PubMed

Tooze, Janet A; Troiano, Richard P; Carroll, Raymond J; Moshfegh, Alanna J; Freedman, Laurence S

2013-06-01

Systematic investigations into the structure of measurement error of physical activity questionnaires are lacking. We propose a measurement error model for a physical activity questionnaire that uses physical activity level (the ratio of total energy expenditure to basal energy expenditure) to relate questionnaire-based reports of physical activity level to true physical activity levels. The 1999-2006 National Health and Nutrition Examination Survey physical activity questionnaire was administered to 433 participants aged 40-69 years in the Observing Protein and Energy Nutrition (OPEN) Study (Maryland, 1999-2000). Valid estimates of participants' total energy expenditure were also available from doubly labeled water, and basal energy expenditure was estimated from an equation; the ratio of those measures estimated true physical activity level ("truth"). We present a measurement error model that accommodates the mixture of errors that arise from assuming a classical measurement error model for doubly labeled water and a Berkson error model for the equation used to estimate basal energy expenditure. The method was then applied to the OPEN Study. Correlations between the questionnaire-based physical activity level and truth were modest (r = 0.32-0.41); attenuation factors (0.43-0.73) indicate that the use of questionnaire-based physical activity level would lead to attenuated estimates of effect size. Results suggest that sample sizes for estimating relationships between physical activity level and disease should be inflated, and that regression calibration can be used to provide measurement error-adjusted estimates of relationships between physical activity and disease.

The Role of Basal Channels in Ice Shelf Calving.

NASA Astrophysics Data System (ADS)

Dow, C. F.; Lee, W. S.; Greenbaum, J. S.; Greene, C. A.; Blankenship, D. D.; Poinar, K.; Forrest, A.; Young, D. A.; Zappa, C. J.

2017-12-01

Increased rates of ice shelf break-up drives acceleration of grounded glacial ice into the ocean, resulting in sea-level rise. Ice shelves are vulnerable to thinning, which make them more susceptible to calving. Here, we examine basal channels under three ice shelves that locally thin the ice and drive formation of transverse ice shelf fractures. The basal channels also cause surface depressions due to hydrostatic buoyancy effects and can draw in surface water to form rivers. These rivers exacerbate thinning by surface melting and hydraulic loading, and can accelerate rifting when they flow into the transverse fractures. Our investigation focuses on Nansen Ice Shelf in the Ross Sea Embayment, East Antarctica. We use ice-sounding radar and single-beam laser altimeter data from two aerogeophysical campaigns conducted in 2011 and 2014, ice surface DEM reconstruction, and satellite imagery analysis, to examine the role of a substantial basal channel in the stability of this ice shelf. Nansen Ice Shelf calved two large icebergs totaling 214 km2 in area in April 2016. The transverse fracture that eventually rifted to form these icebergs initiated directly over the basal channel in 1987. In years when surface water formed on Nansen Ice Shelf, a river flowed into the transverse fracture. In November 2016, we identified a new fracture over the basal channel during in-situ data collection. We compare the Nansen Ice Shelf fractures with those at other vulnerable ice-shelf systems, including Petermann Glacier in Greenland and Totten Glacier in East Antarctica, to evaluate the role that basal channels may play in simultaneous basal and surface weakening and their consequent effect on ice-shelf rifting and stability.

A comparison of basal and eye-flush tears for the analysis of cat tear proteins.

PubMed

Petznick, Andrea; Evans, Margaret D M; Madigan, Michele C; Markoulli, Maria; Garrett, Qian; Sweeney, Deborah F

2011-02-01

To identify a rapid and effective tear collection method providing sufficient tear volume and total protein content (TPC) for analysis of individual proteins in cats. Domestic adult short-haired cats (12-37 months; 2.7-6.6 kg) were used in the study. Basal tears without stimulation and eye-flush tears after instillation of saline (10 μl) were collected using microcapillary tubes from animal eyes either unwounded control or wounded with 9-mm central epithelial debridement giving four groups with n = 3. Tear comparisons were based on total time and rate for tear collection, TPC using micro bicinchoninic acid (BCA), tear immunoglobulin A (IgA), total matrix-metalloproteinase (MMP)-9 concentration using sandwich enzyme-linked immunosorbent assay (ELISA) and MMP-9 activity. Eye-flush tears were collected significantly faster than basal tears in wounded eyes with higher rates for tear collection in unwounded control and wounded eyes. TPC was significantly lower in eye-flush tears compared to basal tears. The relative proportion of tear IgA normalized to TPC (% IgA of TPC) was not significantly different between basal and eye-flush tears. In unwounded control eyes, MMP-9 was slightly higher in eye-flush than in basal tears; activity of MMP-9 in both tear types was similar. In wounded eyes, eye-flush tears showed highest MMP-9 levels and activity on Day 1, which subsequently decreased to Day 7. MMP-9 activity in basal tears from wounded eyes did not display changes in expression. Eye-flush tears can be collected rapidly providing sufficient tear volume and TPC. This study also indicates that eye-flush tears may be more suitable than basal tears for the analysis of MMPs following corneal wounding. © 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.

Morphological evidence and direct estimates of rapid melting beneath Totten Glacier Ice Shelf, East Antarctica

NASA Astrophysics Data System (ADS)

Greenbaum, Jamin; Schroeder, Dustin; Grima, Cyril; Habbal, Feras; Dow, Christine; Roberts, Jason; Gwyther, David; van Ommen, Tas; Siegert, Martin; Blankenship, Donald

2017-04-01

Totten Glacier drains at least 3.5 meters of eustatic sea level potential from marine-based ice in the Aurora Subglacial Basin (ASB) in East Antarctica, more than the combined total of all glaciers in West Antarctica. Totten Glacier has been the most rapidly thinning glacier in East Antarctica since satellite altimetry time series began and the nature of the thinning suggests that it is driven by enhanced basal melting due to ocean processes. While grounded ice thinning rates have been steady, recent work has shown that Totten's floating ice shelf may not have the same thinning behavior; as a result, it is critical to observe ice shelf and cavity boundary conditions and basal processes to understand this apparent discrepancy. Warm Modified Circumpolar Deep Water (MCDW), which has been linked to glacier retreat in West Antarctica, has been observed in summer and winter on the nearby Sabrina Coast continental shelf and deep depressions in the seafloor provide access for MCDW to reach the ice shelf cavity. Given its northern latitude, numerical ice sheet modeling indicates that Totten Glacier may be prone to retreat caused by hydrofracture in a warming climate, so it is important to understand how intruding MCDW is affecting thinning of Totten Glacier's ice shelf. Here we use post-processed, focused airborne radar observations of the Totten Glacier Ice Shelf to delineate multi-km wide basal channels and flat basal terraces associated with high basal reflectivity and specularity (flatness) anomalies and correspondingly large ice surface depressions that indicate active basal melting. Using a simple temperature-attenuation model, and basal roughness corrections, we present basal melt rates associated with the radar reflection and specularity anomalies and compare them to those derived from numerical ocean circulation modeling and an ice flow divergence calculation. Sub-ice shelf ocean circulation modeling and under-ice robotic observations of Pine Island Glacier Ice Shelf in West Antarctica and the Petermann Glacier Ice Shelf in Greenland have shown that basal terraces associated with large basal channels are an indication of rapidly melting ice shelves. In this context, these new results identify an East Antarctic example of rapid basal melting processes and demonstrate that airborne radar can be used to identify basal characteristics and processes relevant to ice shelf stability.

Autoadjusting-CPAP effect on serum Leptin concentrations in Obstructive Sleep Apnoea patients

PubMed Central

Drummond, Marta; Winck, João C; Guimarães, João T; Santos, Ana C; Almeida, João; Marques, José A

2008-01-01

Background Leptin is an hormone that regulates body weight. Studies have shown increasing leptin concentrations according to body mass index (BMI) and intermittent hypoxia. Our aim is to evaluate the basal leptin levels in OSA patients and its possible relation to OSA severity, independently of confounders and investigate the Autoadjusting-CPAP effect on leptin values. Methods In ninety eight male patients with moderate to severe OSA leptin serum levels were evaluated before therapy, 9 days and 6 months after therapy. Results In this group mean age was 55.3 years, mean BMI was 33.2 Kg/m2 and mean Apnoea- Hypopnea Index (AHI) was 51.7/h. Mean basal serum leptin value was 12.1 ug/L. Univariate analysis showed a significant correlation between serum leptin values and BMI (R = 0.68; p < 0.001), waist-hip ratio (R = 0.283; p = 0.004) and AHI (R = 0.198; p = 0.048); in stepwise multiple regression analysis only BMI (p < 0.001) was a predictor of serum leptin values. One week after therapy, mean leptin serum level decreased to 11.0 ug/L and 6 months after it was 11.4 ug/L. (p = 0.56 and p = 0.387, respectively) Conclusion Baseline leptin serum levels positively correlate with BMI, fat distributioand OSA severity. BMI is the only predictor of basal leptin levels. Treatment with Autoadjusting-CPAP has a small effect on leptin levels. PMID:18828917

Suppression of gastrin release and gastric secretion by gastric inhibitory polypeptide (GIP) and vasoactive intestinal polypeptide (VIP).

PubMed Central

Villar, H V; Fender, H R; Rayford, P L; Bloom, S R; Ramus, N I; Thompson, J C

1976-01-01

Five dogs prepared with Heidenhain pouches received infusions of saline, GIP and VIP before and after a standard meat meal. Blood samples were obtained under basal conditions and at subsequent intervals for measurement of gastrin, insulin, GIP and VIP by radioimmunoassay. GIP and VIP infusions had no effect on basal levels of gastrin. GIP and VIP (in common with secretin and glucagon) were found to suppress food-stimulated release of gastrin and gastrin-stimulated acid secretion from the Heidenhain pouch. Insulin levels were significantly elevated during GIP and VIP infusions. Food released GIP (and perhaps VIP. PMID:938120

Is applicable thermodynamics of negative temperature for living organisms?

NASA Astrophysics Data System (ADS)

Atanasov, Atanas Todorov

2017-11-01

During organismal development the moment of sexual maturity can be characterizes by nearly maximum basal metabolic rate and body mass. Once the living organism reaches extreme values of the mass and the basal metabolic rate, it reaches near equilibrium thermodynamic steady state physiological level with maximum organismal complexity. Such thermodynamic systems that reach equilibrium steady state level at maximum mass-energy characteristics can be regarded from the prospective of thermodynamics of negative temperature. In these systems the increase of the internal and free energy is accompanied with decrease of the entropy. In our study we show the possibility the living organisms to regard as thermodynamic system with negative temperature

Effect of perinatal asphyxia and carbamazepine treatment on cortical dopamine and DOPAC levels.

PubMed

López-Pérez, Silvia J; Morales-Villagrán, Alberto; Medina-Ceja, Laura

2015-02-13

One of the most important manifestations of perinatal asphyxia is the occurrence of seizures, which are treated with antiepileptic drugs, such as carbamazepine. These early seizures, combined with pharmacological treatments, may influence the development of dopaminergic neurotransmission in the frontal cortex. This study aimed to determine the extracellular levels of dopamine and its main metabolite DOPAC in 30-day-old rats that had been asphyxiated for 45 min in a low (8%) oxygen chamber at a perinatal age and treated with daily doses of carbamazepine. Quantifications were performed using microdialysis coupled to a high-performance liquid chromatography (HPLC) system in basal conditions and following the use of the chemical stimulus. Significant decreases in basal and stimulated extracellular dopamine and DOPAC content were observed in the frontal cortex of the asphyxiated group, and these decreases were partially recovered in the animals administered daily doses of carbamazepine. Greater basal dopamine concentrations were also observed as an independent effect of carbamazepine. Perinatal asphyxia plus carbamazepine affects extracellular levels of dopamine and DOPAC in the frontal cortex and stimulated the release of dopamine, which provides evidence for the altered availability of dopamine in cortical brain areas during brain development.

[Effect of acute hypoxia on the intensity of free radical processes in the basal nuclei of the brain, and the rat behaviour in the open field test under conditions of altered photoperiod].

PubMed

Sopova, I Iu; Zamorskiĭ, I I

2011-03-01

The effect of acute hypoxia on the intensity of free radical processes in the basal nuclei (the nucleus caudatus, globus pallidus. nucleus accumbens. amygdaloid complex) of the brain, and the rat behaviour in the open field test has been studied under conditions of altered photoperiod. It has been shown that constant darkness levels the effect of acute hypoxia on the intensity of lipid peroxidation, preserves the activity of superoxide dismutase and catalase at a higher level, lowers the activity of glutathione peroxidase. Under light, the sensitivity of basal nuclei neurons to acute hypoxia is enhanced, the latter being reflected in intensification of lipid peroxidation at the expense of increased formation of dien conjugates. The activity of catalase at that considerably exceeds the level of even intact rats in all the structures. It has been established that an altered photoperiod modulates the effect of acute hypoxia on the parameters of rat's activity in the open field, the character of their change depending on the nature of a photophase change.

Differential effects of cyclic and constant stress on ATP release and mucociliary transport by human airway epithelia

PubMed Central

Button, Brian; Picher, Maryse; Boucher, Richard C

2007-01-01

In the lungs, the first line of defence against bacterial infection is the thin layer of airway surface liquid (ASL) lining the airway surface. The superficial airway epithelium exhibits complex regulatory pathways that blend ion transport to adjust ASL volume to maintain proper mucociliary clearance (MCC). We hypothesized that stresses generated by airflow and transmural pressures during breathing govern ASL volume by regulating the rate of epithelial ATP release. Luminal ATP, via interactions with apical membrane P2-purinoceptors, regulates the balance of active ion secretion versus absorption to maintain ASL volume at optimal levels for MCC. In this study we tested the hypothesis that cyclic compressive stress (CCS), mimicking normal tidal breathing, regulates ASL volume in airway epithelia. Polarized tracheobronchial epithelial cultures from normal and cystic fibrosis (CF) subjects responded to a range of CCS by increasing the rate of ATP release. In normal airway epithelia, the CCS-induced increase in ASL ATP concentration was sufficient to induce purinoceptor-mediated increases in ASL height and MCC, via inhibition of epithelial Na+-channel-mediated Na+ absorption and stimulation of Cl− secretion through CFTR and the Ca2+-activated chloride channels. In contrast, static, non-oscillatory stress did not stimulate ATP release, ion transport or MCC, emphasizing the importance of rhythmic mechanical stress for airway defence. In CF airway cultures, which exhibit basal ASL depletion, CCS was partially effective, producing less ASL volume secretion than in normal cultures, but a level sufficient to restore MCC. The present data suggest that CCS may (1) regulate ASL volume in the normal lung and (2) improve clearance in the lungs of CF patients, potentially explaining the beneficial role of exercise in lung defence. PMID:17317749

Effect of hypothyroidism on insulin sensitivity and glucose tolerance in dogs.

PubMed

Hofer-Inteeworn, Natalie; Panciera, David L; Monroe, William E; Saker, Korinn E; Davies, Rebecca Hegstad; Refsal, Kent R; Kemnitz, Joseph W

2012-04-01

To determine the effects of hypothyroidism on insulin sensitivity, glucose tolerance, and concentrations of hormones counter-regulatory to insulin in dogs. 8 anestrous mixed-breed bitches with experimentally induced hypothyroidism and 8 euthyroid control dogs. The insulin-modified frequently sampled IV glucose tolerance test and minimal model analysis were used to determine basal plasma insulin and glucose concentrations, acute insulin response to glucose, insulin sensitivity, glucose effectiveness, and disposition index. Growth hormone response was assessed by stimulation and suppression tests. Additionally, basal serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) concentrations and urine cortisol-to-creatinine concentration ratios were measured and dual energy x-ray absorptiometry was performed to evaluate body composition. Insulin sensitivity was lower in the hypothyroid group than in the euthyroid group, whereas acute insulin response to glucose was higher. Glucose effectiveness and disposition index were not different between groups. Basal serum GH and IGF-1 concentrations as well as abdominal fat content were high in hypothyroid dogs, but urine cortisol-to-creatinine concentration ratios were unchanged. Hypothyroidism appeared to negatively affect glucose homeostasis by inducing insulin resistance, but overall glucose tolerance was maintained by increased insulin secretion in hypothyroid dogs. Possible factors affecting insulin sensitivity are high serum GH and IGF-1 concentrations and an increase in abdominal fat. In dogs with diseases involving impaired insulin secretion such as diabetes mellitus, concurrent hypothyroidism can have important clinical implications.

Gait variability and basal ganglia disorders: stride-to-stride variations of gait cycle timing in Parkinson's disease and Huntington's disease

NASA Technical Reports Server (NTRS)

Hausdorff, J. M.; Cudkowicz, M. E.; Firtion, R.; Wei, J. Y.; Goldberger, A. L.

1998-01-01

The basal ganglia are thought to play an important role in regulating motor programs involved in gait and in the fluidity and sequencing of movement. We postulated that the ability to maintain a steady gait, with low stride-to-stride variability of gait cycle timing and its subphases, would be diminished with both Parkinson's disease (PD) and Huntington's disease (HD). To test this hypothesis, we obtained quantitative measures of stride-to-stride variability of gait cycle timing in subjects with PD (n = 15), HD (n = 20), and disease-free controls (n = 16). All measures of gait variability were significantly increased in PD and HD. In subjects with PD and HD, gait variability measures were two and three times that observed in control subjects, respectively. The degree of gait variability correlated with disease severity. In contrast, gait speed was significantly lower in PD, but not in HD, and average gait cycle duration and the time spent in many subphases of the gait cycle were similar in control subjects, HD subjects, and PD subjects. These findings are consistent with a differential control of gait variability, speed, and average gait cycle timing that may have implications for understanding the role of the basal ganglia in locomotor control and for quantitatively assessing gait in clinical settings.

Simulation-Based Evaluation of Dose-Titration Algorithms for Rapid-Acting Insulin in Subjects with Type 2 Diabetes Mellitus Inadequately Controlled on Basal Insulin and Oral Antihyperglycemic Medications.

PubMed

Ma, Xiaosu; Chien, Jenny Y; Johnson, Jennal; Malone, James; Sinha, Vikram

2017-08-01

The purpose of this prospective, model-based simulation approach was to evaluate the impact of various rapid-acting mealtime insulin dose-titration algorithms on glycemic control (hemoglobin A1c [HbA1c]). Seven stepwise, glucose-driven insulin dose-titration algorithms were evaluated with a model-based simulation approach by using insulin lispro. Pre-meal blood glucose readings were used to adjust insulin lispro doses. Two control dosing algorithms were included for comparison: no insulin lispro (basal insulin+metformin only) or insulin lispro with fixed doses without titration. Of the seven dosing algorithms assessed, daily adjustment of insulin lispro dose, when glucose targets were met at pre-breakfast, pre-lunch, and pre-dinner, sequentially, demonstrated greater HbA1c reduction at 24 weeks, compared with the other dosing algorithms. Hypoglycemic rates were comparable among the dosing algorithms except for higher rates with the insulin lispro fixed-dose scenario (no titration), as expected. The inferior HbA1c response for the "basal plus metformin only" arm supports the additional glycemic benefit with prandial insulin lispro. Our model-based simulations support a simplified dosing algorithm that does not include carbohydrate counting, but that includes glucose targets for daily dose adjustment to maintain glycemic control with a low risk of hypoglycemia.

The role of Toujeo®, insulin glargine U-300, in the treatment of diabetes mellitus.

PubMed

Brown, Meagan A; Davis, Courtney S; Fleming, Laurie W; Fleming, Joshua W

2016-09-01

The purpose of this article is to educate nurse practitioners about the role of Toujeo®, insulin glargine U-300 (Gla-300), which is a new option for the treatment of diabetes mellitus. A comprehensive literature search was conducted using MEDLINE with the key terms: insulin glargine 300, Toujeo, Gla-300, and EDITION for clinical trial data. Other resources included package inserts, drug information websites, and the World Health Organization (WHO). Gla-300 appears to be a safe and effective option for basal insulin therapy. In clinical trials, it was shown to be equally efficacious as Gla-100 with fewer episodes of hypoglycemia and slightly less weight gain, and subjects receiving Gla-300 required approximately 10 units more basal insulin to obtain the same hemoglobin A1c (HbA1c) as subjects receiving Gla-100. This new basal therapy option represents a potential advantage for patients who require higher doses of insulin because of the higher concentration of Gla-300. The lower incidence of hypoglycemia and more predictable pharmacokinetics could offer a significant therapeutic benefit in difficult-to-control patients with diabetes mellitus. The biggest disadvantage of this product is the slightly higher insulin dosage that is required to improve and/or maintain patients' HbA1c. ©2016 American Association of Nurse Practitioners.

Insulin Glargine 300 U/mL: A Review in Diabetes Mellitus.

PubMed

Blair, Hannah A; Keating, Gillian M

2016-03-01

Insulin glargine 300 U/mL (Toujeo(®)) is a long-acting basal insulin analogue approved for the treatment of diabetes mellitus. Insulin glargine 300 U/mL has a more stable and prolonged pharmacokinetic/pharmacodynamic profile than insulin glargine 100 U/mL (Lantus(®)), with a duration of glucose-lowering activity exceeding 24 h. In several 6-month phase III trials, insulin glargine 300 U/mL achieved comparable glycaemic control to that seen with insulin glargine 100 U/mL in patients with type 1 or type 2 diabetes, albeit with consistently higher daily basal insulin requirements. These improvements in glycaemic control were maintained during longer-term (12 months) treatment. Insulin glargine 300 U/mL was generally associated with a lower risk of nocturnal hypoglycaemia than insulin glargine 100 U/mL in insulin-experienced patients with type 2 diabetes, while the risk of nocturnal hypoglycaemia did not significantly differ between treatment groups in insulin-naïve patients with type 2 diabetes or in patients with type 1 diabetes. To conclude, once-daily subcutaneous insulin glargine 300 U/mL is an effective and generally well tolerated basal insulin therapy option for patients with type 1 or type 2 diabetes.

The use of vismodegib to shrink keratocystic odontogenic tumors in patients with basal cell nevus syndrome.

PubMed

Ally, Mina S; Tang, Jean Y; Joseph, Timmy; Thompson, Bobbye; Lindgren, Joselyn; Raphael, Maria Acosta; Ulerio, Grace; Chanana, Anita M; Mackay-Wiggan, Julian M; Bickers, David R; Epstein, Ervin H

2014-05-01

Keratocystic odontogenic tumors (KCOTs) of the jaw affect more than 65% of patients with basal cell nevus syndrome (BCNS). Surgery frequently causes facial disfigurement and is not always curative. Most BCNS-related and some sporadic KCOTs have malignant activation of the Hedgehog signaling pathway. We examined the effect of vismodegib (an oral Hedgehog pathway inhibitor) on KCOT size in patients with BCNS enrolled in a clinical trial testing vismodegib for basal cell carcinoma prevention (NCT00957229), using pretreatment and posttreatment magnetic resonance imaging. Four men and 2 women had pretreatment KCOTs (mean longest diameter, 2.0 cm; range, 0.7-3.3 cm), occurring primarily in the mandible. Patients were treated with vismodegib, 150 mg/d, for a mean (SD) of 18.0 (4.8) months (range, 11-24 months). Four patients experienced a size reduction and 2 had no change. Vismodegib reduced the mean longest diameter of KCOTs in all patients by 1.0 cm (95% CI, 0.03-1.94; P = .02) or 50% from baseline. We observed no enlargement of existing KCOTs or new KCOT development. Vismodegib shrinks some KCOTs in patients with BCNS and may offer an alternative to surgical therapy. These effects were maintained for at least 9 months after drug cessation in 1 patient. Further studies assessing long-term efficacy and optimal maintenance regimens should be performed.

Altered Effective Connectivity Network of the Basal Ganglia in Low-Grade Hepatic Encephalopathy: A Resting-State fMRI Study with Granger Causality Analysis

PubMed Central

Zhong, Jianhui; Zhang, Zhiqiang; Ni, Ling; Jiao, Qing; Liao, Wei; Zheng, Gang; Lu, Guangming

2013-01-01

Background The basal ganglia often show abnormal metabolism and intracranial hemodynamics in cirrhotic patients with hepatic encephalopathy (HE). Little is known about how the basal ganglia affect other brain system and is affected by other brain regions in HE. The purpose of this study was to investigate whether the effective connectivity network associated with the basal ganglia is disturbed in HE patients by using resting-state functional magnetic resonance imaging (rs-fMRI). Methodology/Principal Findings Thirty five low-grade HE patients and thirty five age- and gender- matched healthy controls participated in the rs-fMRI scans. The effective connectivity networks associated with the globus pallidus, the primarily affected region within basal ganglia in HE, were characterized by using the Granger causality analysis and compared between HE patients and healthy controls. Pearson correlation analysis was performed between the abnormal effective connectivity and venous blood ammonia levels and neuropsychological performances of all HE patients. Compared with the healthy controls, patients with low-grade HE demonstrated mutually decreased influence between the globus pallidus and the anterior cingulate cortex (ACC), cuneus, bi-directionally increased influence between the globus pallidus and the precuneus, and either decreased or increased influence from and to the globus pallidus in many other frontal, temporal, parietal gyri, and cerebellum. Pearson correlation analyses revealed that the blood ammonia levels in HE patients negatively correlated with effective connectivity from the globus pallidus to ACC, and positively correlated with that from the globus pallidus to precuneus; and the number connectivity test scores in patients negatively correlated with the effective connectivity from the globus pallidus to ACC, and from superior frontal gyrus to globus pallidus. Conclusions/Significance Low-grade HE patients had disrupted effective connectivity network of basal ganglia. Our findings may help to understand the neurophysiological mechanisms underlying the HE. PMID:23326484

Activity of the rat osteocalcin basal promoter in osteoblastic cells is dependent upon homeodomain and CP1 binding motifs.

PubMed

Towler, D A; Bennett, C D; Rodan, G A

1994-05-01

A detailed analysis of the transcriptional machinery responsible for osteoblast-specific gene expression should provide tools useful for understanding osteoblast commitment and differentiation. We have defined three cis-elements important for basal activity of the rat osteocalcin (OC) promoter, located at about -200 to -180, -170 to -138, and -121 to -64 relative to the transcription initiation site. A motif (TCTGATTGTGT) present in the region between -200 and -170 that binds a multisubunit CP1/NFY/CBF-like CAAT factor complex contributes significantly to high level basal activity and presumably functions as the CAAT box for the rat OC promoter. We show that the region -121 to 32 is sufficient to confer osteoblastic cell type specificity in transient transfection assays of cultured cell lines using luciferase as a reporter. The basal promoter is active in rodent osteoblastic cell lines, but not in rodent fibroblastic or muscle cell lines. Although the rat OC box (-100 to -74) contains a CAAT motif, we could not detect CP1-like CAAT factor binding to this region. In fact, we demonstrate that a Msx-1 (Hox 7.1) homeodomain binding motif (ACTAATTG; bottom strand) in the 3'-end of the rat OC box is necessary for high level activity of the rat OC basal promoter in osteoblastic cells. A nuclear factor that recognizes this motif appears to be present in osteoblastic ROS 17/2.8 cells, which produce OC, but not in fibroblastic ROS 25/1 cells, which fail to express OC. This ROS 17/2.8 nuclear factor also recognizes the A/T-rich DNA cognates of the homeodomain-containing POU family of transcription factors. Taken together, these data suggest that a ubiquitous CP1-like CAAT factor and a cell type-restricted homeodomain containing (Msx or POU family) transcription factor interact with the proximal rat OC promoter to direct appropriate basal OC transcription in osteoblastic cells.

Criteria for Seismic Splay Fault Activation During Subduction Earthquakes

NASA Astrophysics Data System (ADS)

Dedontney, N.; Templeton, E.; Bhat, H.; Dmowska, R.; Rice, J. R.

2008-12-01

As sediment is added to the accretionary prism or removed from the forearc, the material overlying the plate interface must deform to maintain a wedge structure. One of the ways this internal deformation is achieved is by slip on splay faults branching from the main detachment, which are possibly activated as part of a major seismic event. As a rupture propagates updip along the plate interface, it will reach a series of junctions between the shallowly dipping detachment and more steeply dipping splay faults. The amount and distribution of slip on these splay faults and the detachment determines the seafloor deformation and the tsunami waveform. Numerical studies by Kame et al. [JGR, 2003] of fault branching during dynamic slip-weakening rupture in 2D plane strain showed that branch activation depends on the initial stress state, rupture velocity at the branching junction, and branch angle. They found that for a constant initial stress state, with the maximum principal stress at shallow angles to the main fault, branch activation is favored on the compressional side of the fault for a range of branch angles. By extending the part of their work on modeling the branching behavior in the context of subduction zones, where critical taper wedge concepts suggest the angle that the principal stress makes with the main fault is shallow, but not horizontal, we hope to better understand the conditions for splay fault activation and the criteria for significant moment release on the splay. Our aim is to determine the range of initial stresses and relative frictional strengths of the detachment and splay fault that would result in seismic splay fault activation. In aid of that, we conduct similar dynamic rupture analyses to those of Kame et al., but use explicit finite element methods, and take fuller account of overall structure of the zone (rather than focusing just on the branching junction). Critical taper theory requires that the basal fault be weaker than the overlying material, so we build on previous work by incorporating the effect of strength contrasts between the basal and splay faults. The relative weakness of the basal fault is often attributed to high pore pressures, which lowers the effective normal stress and brings the basal fault closer to failure. We vary the initial stress state, while maintaining a constant principal stress orientation, to see how the closeness to failure affects the branching behavior for a variety of branch step-up angles.

A 10-Year Evaluation of Prescribed Winter Burns in Uneven-Aged Stands of Pinus taeda L. and P. echinata Mill.: Woody Understorey Vegetation Response

Treesearch

Michael D. Cain

1993-01-01

Abstract.The effects of burning cycles and pine basal area levels were assessed on natural pine regeneration and hardwood development in uneven-aged stands of loblolly andshortleafpines (Pinw taeda L. and P. echinata Mill.). The treatments included an unburned control and prescribed winter burrs at 3-, 6-, and 9-yr intervals. Basal area treatments were 9, 14, 18, and...

Single and Combined Effects of Deoxynivalenol Mycotoxin and a Microbial Feed Additive on Lymphocyte DNA Damage and Oxidative Stress in Broiler Chickens

PubMed Central

Awad, Wageha A.; Ghareeb, Khaled; Dadak, Agnes; Hess, Michael; Böhm, Josef

2014-01-01

The immune and intestinal epithelial cells are particularly sensitive to the toxic effects of deoxynivalenol (DON). The aim of this experiment was to study the effects of DON and/or a microbial feed additive on the DNA damage of blood lymphocytes and on the level of thiobarbituric acid reactive substance (TBARS) as an indicator of lipid peroxidation and oxidative stress in broilers. A total of forty 1-d-old broiler chicks were randomly assigned to 1 of 4 dietary treatments (10 birds per group) for 5 wk. The dietary treatments were 1) basal diet; 2) basal diet contaminated with 10 mg DON/kg feed; 3) basal diet contaminated with 10 mg DON/kg feed and supplemented with 2.5 kg/ton of feed of Mycofix Select; 4) basal diet supplemented with Mycofix Select (2.5 kg/ton of feed). At the end of the feeding trial, blood were collected for measuring the level of lymphocyte DNA damage of blood and the TBARS level was measured in plasma, heart, kidney, duodenum and jejunum. The dietary exposure of DON caused a significant increase (P = 0.001) of DNA damage in blood lymphocytes (31.99±0.89%) as indicated in the tail of comet assay. Interestingly addition of Mycofix Select to DON contaminated diet decreased (P = 0.001) the DNA damage (19.82±1.75%) induced by DON. In order to clarify the involvement of lipid peroxidation in the DNA damage of DON, TBARS levels was measured. A significant increase (P = 0.001) in the level of TBARS (23±2 nmol/mg) was observed in the jejunal tissue suggesting that the lipid peroxidation might be involved in the DNA damage. The results indicate that DON is cytotoxic and genotoxic to the chicken intestinal and immune cells and the feed additive have potential ability to prevent DNA damage induced by DON. PMID:24498242

Hypoxia Induces an Increase in Intracellular Magnesium via Transient Receptor Potential Melastatin 7 (TRPM7) Channels in Rat Hippocampal Neurons in Vitro*

PubMed Central

Zhang, Jing; Zhao, Fengbo; Zhao, Yin; Wang, Jing; Pei, Lei; Sun, Ning; Shi, Jing

2011-01-01

TRPM7, a divalent cation channel, plays an important role in neurons damaged from cerebral ischemia due to permitting intracellular calcium overload. This study aimed to explore whether magnesium was transported via a TRPM7 channel into the intracellular space of rat hippocampal neurons after 1 h of oxygen-glucose deprivation (OGD) and acute chemical ischemia (CI) by using methods of the Mg2+ fluorescent probe Mag-Fura-2 to detect intracellular magnesium concentration ([Mg2+]i) and flame atomic absorption spectrometry to measure extracellular magnesium concentration ([Mg2+]o). The results showed that the neuronal [Mg2+]i was 1.51-fold higher after 1 h of OGD at a basal level, and the increase of neuronal [Mg2+]i reached a peak after 1 h of OGD and was kept for 60 min with re-oxygenation. Meanwhile, the [Mg2+]o decreased after 1 h of OGD and recovered to the pre-ischemic level within 15 min after re-oxygenation. In the case of CI, the [Mg2+]i peak immediately appeared in hippocampal neurons. This increase of [Mg2+]i declined by removing extracellular magnesium in OGD or CI. Furthermore, by using Gd3+ or 2-aminoethoxydiphenyl borate to inhibit TRPM7 channels, the [Mg2+]i increase, which was induced by OGD or CI, was attenuated without altering the basal level of [Mg2+]i. By silencing TRPM7 with shRNA in hippocampal neurons, it was found that not only was the increase of [Mg2+]i induced by OGD or CI but also the basal levels of [Mg2+]i were attenuated. In contrast, overexpression of TRPM7 in HEK293 cells exaggerated both the basal levels and increased [Mg2+]i after 1 h of OGD/CI. These results suggest that anoxia induced the increase of [Mg2+]i via TRPM7 channels in rat hippocampal neurons. PMID:21487014

Gravity Perception in a Cladoceran-zooplankter: Anatomy of Antennal Socket Setae of Daphnia Magna

NASA Technical Reports Server (NTRS)

Meyers, D. G.

1985-01-01

Night orientation in Daphnia magna was recently associated with setae on the basal socket of the swimming antennae. Daphnids are suspected of maintaining nocturnal equilibrium by monitoring the gravity vector through upward setal deflections caused by sinking between antennal swimming strokes. Setae appear to be hydrodynamic rheoceptors that sense the gravity vector indirectly by mechanoreceptivity to the direction and velocity of water currents. Neuroanatomical stains have revealed cell bodies at the base of the setal shafts, dendritic connections through to the distal ends of the shafts, and axonal tracts around the antennal socket connecting with an additional cell body and continuing toward the brain. These anatomical observations combined with previous scanning electron microscopy studies suggest that the setae are similar to mechanoreceptors and propreceptors used by higher crustaceans to sense water currents and gravity, and maintained balance.

The neural substrates of driving at a safe distance: a functional MRI study.

PubMed

Uchiyama, Yuji; Ebe, Kazutoshi; Kozato, Akio; Okada, Tomohisa; Sadato, Norihiro

2003-12-11

An important driving skill is the ability to maintain a safe distance from a preceding car. To determine the neural substrates of this skill we performed functional magnetic resonance imaging of simulated driving in 21 subjects. Subjects used a joystick to adjust their own driving speed in order to maintain a constant distance from a preceding car traveling at varying speeds. The task activated multiple brain regions. Activation of the cerebellum may reflect visual feedback during smooth tracking of the preceding car. Co-activation of the basal ganglia, thalamus and premotor cortex is related to movement selection. Activation of a premotor-parietal network is related to visuo-motor co-ordination. Task performance was negatively correlated with anterior cingulate activity, consistent with the role of this region in error detection and response selection.

Leptin-induced basal Akt phosphorylation and its implication in exercise-mediated improvement of insulin sensitivity.

PubMed

Zheng, Xianjie; Niu, Sen

2018-01-29

Physical exercise is an efficient therapeutical tool in the management of insulin resistance (IR) and related metabolic diseases. Leptin, the well-known obesity hormone and the absence of which leads to IR, showed controversial effects on IR as research continues. Thus, in this study, a detailed investigation of the effect of leptin on exercise-mediated improvement of insulin sensitivity and its underlying mechanism was carried out. Using a rat model of chronic or acute swimming exercise training, we found that serum leptin increased 1 h after either acute exercise or the last session of chronic exercise, when impaired insulin action was observed in previous reports. However, chronic exercise reducd basal serum leptin levels and promoted insulin sensitivity compared with sedentary controls or rats subjected to one bout of aerobic exercise. Our animal results indicated the potential linkage between leptin and insulin sensitivity, which is further investigated in the skeletal muscle L6 cells. Leptin treatment in L6 cells promoted the basal levels of insulin signaling as well as glucose uptake, while blocking JAK2 signaling with either pharmacological intervention (JAK2 inhibitor AG490) or genetic manipulation (siRNA knockdown) decreased the basal levels of insulin signaling. Furthermore, leptin treatment inhibited insulin-stimulated insulin signaling and glucose uptake, while blocking JAK2 signaling restored leptin-attenuated insulin sensitivity. Taken together, our results demonstrated that reduced serum leptin, at least in part, contributes to exercise-mediated improvement of insulin sensitivity, indicating JAK2 as a potent therapeutical target of insulin resistance. Copyright © 2018 Elsevier Inc. All rights reserved.

Enhanced basal activation of mitogen-activated protein kinases in adipocytes from type 2 diabetes: potential role of p38 in the downregulation of GLUT4 expression.

PubMed

Carlson, Christian J; Koterski, Sandra; Sciotti, Richard J; Poccard, German Braillard; Rondinone, Cristina M

2003-03-01

Serine and threonine kinases may contribute to insulin resistance and the development of type 2 diabetes. To test the potential for members of the mitogen-activated protein (MAP) kinase family to contribute to type 2 diabetes, we examined basal and insulin-stimulated Erk 1/2, JNK, and p38 phosphorylation in adipocytes isolated from healthy and type 2 diabetic individuals. Maximal insulin stimulation increased the phosphorylation of Erk 1/2 and JNK in healthy control subjects but not type 2 diabetic patients. Insulin stimulation did not increase p38 phosphorylation in either healthy control subjects or type 2 diabetic patients. In type 2 diabetic adipocytes, the basal phosphorylation status of these MAP kinases was significantly elevated and was associated with decreased IRS-1 and GLUT4 in these fat cells. To determine whether MAP kinases were involved in the downregulation of IRS-1 and GLUT4 protein levels, selective inhibitors were used to inhibit these MAP kinases in 3T3-L1 adipocytes treated chronically with insulin. Inhibition of Erk 1/2, JNK, or p38 had no effect on insulin-stimulated reduction of IRS-1 protein levels. However, inhibition of the p38 pathway prevented the insulin-stimulated decrease in GLUT4 protein levels. In summary, type 2 diabetes is associated with an increased basal activation of the MAP kinase family. Furthermore, upregulation of the p38 pathway might contribute to the loss of GLUT4 expression observed in adipose tissue from type 2 diabetic patients.

Ground-Water Availability from the Hawi Aquifer in the Kohala Area, Hawaii

USGS Publications Warehouse

Underwood, Mark R.; Meyer, William; Souza, William R.

1995-01-01

A ground-water study consisting of test-well drilling, aquifer tests, and numerical simulation was done to investigate ground-water availability in the basal part of the Hawi aquifer between the western drainage divide of Pololu Valley and Upolu Point in Kohala, Hawaii. The test-well drilling provided information on geology, water levels, water quality, vertical extent of the freshwater, and the thickness of the freshwater-saltwater transition zone in that aquifer. A total of 12 test wells were drilled at eight locations. Aquifer tests were done at five locations to estimate the hydraulic conductivity of the aquifer. Using information on the distribution of recharge, vertical extent of freshwater, hydraulic conductivity, and geometry of the basal aquifer, a numerical model was used to simulate the movement of water into, through, and out of the basal aquifer, and the effect of additional pumping on the water levels in the aquifer. Results of the modeling indicate that ground-water withdrawal of 20 million gallons per day above the existing withdrawal of 0.6 million gallons per day from the basal aquifer is hydrologically feasible, but that spacing, depth, and pumping rates of individual wells are important. If pumping is concentrated, the likelihood of saltwater intrusion is increased. The additional withdrawal of 20 million gallons per day would result in a reduction of ground-water discharge to the ocean by an amount equal to pumpage. Although model-calculated declines in water-level outside the area of pumping are small, pumping could cause some reduction of streamflow near the mouth of Pololu Stream.

Effect of partial supplementation of sun-dried Azolla as a protein source on the immunity and antioxidant status of commercial broilers.

PubMed

Chichilichi, Biswal; Mohanty, G P; Mishra, S K; Pradhan, C R; Behura, N C; Das, A; Behera, K

2015-09-01

The present study was conducted to evaluate the effect of partial supplementation of sun-dried Azolla as a protein source on the immunity of commercial broilers in coastal Odisha. A 180 day-old broiler chicks were distributed in six dietary treatments viz. C1: Basal diet, C2: Basal diet + enzyme, T1: Basal diet +5% protein from Azolla, T2: Basal diet + 5% protein from Azolla + enzyme, T3: Basal diet +10% protein from Azolla, and T4: Basal diet + 10% protein from Azolla + enzyme. Cutaneous basophilc hypersensitivity (CBH) and humoral immunity response were determined at the 38(th) day of age. At 42(nd) day, the weight of lymphoid organs, an antioxidant enzyme, and lipid peroxidation activity were determined. The CBH response did not differ significantly among the treated groups, but the sheep red blood cells response was significantly higher in T4. The weight of lymphoid organs or immune organs of all the treated groups did not differ significantly (p>0.05). The erythrocyte catalase level of T4 group was found to be significantly higher than rest of the treated groups except T3. It may be concluded that supplementation of Azolla at 10% of dietary protein requirement along with enzyme supplementation in an isonitrogenous diet showed a better immune response in broilers.

Effect of partial supplementation of sun-dried Azolla as a protein source on the immunity and antioxidant status of commercial broilers

PubMed Central

Chichilichi, Biswal; Mohanty, G. P.; Mishra, S. K.; Pradhan, C. R.; Behura, N. C.; Das, A.; Behera, K.

2015-01-01

Aim: The present study was conducted to evaluate the effect of partial supplementation of sun-dried Azolla as a protein source on the immunity of commercial broilers in coastal Odisha. Materials and Methods: A 180 day-old broiler chicks were distributed in six dietary treatments viz. C1: Basal diet, C2: Basal diet + enzyme, T1: Basal diet +5% protein from Azolla, T2: Basal diet + 5% protein from Azolla + enzyme, T3: Basal diet +10% protein from Azolla, and T4: Basal diet + 10% protein from Azolla + enzyme. Cutaneous basophilc hypersensitivity (CBH) and humoral immunity response were determined at the 38th day of age. At 42nd day, the weight of lymphoid organs, an antioxidant enzyme, and lipid peroxidation activity were determined. Results: The CBH response did not differ significantly among the treated groups, but the sheep red blood cells response was significantly higher in T4. The weight of lymphoid organs or immune organs of all the treated groups did not differ significantly (p>0.05). The erythrocyte catalase level of T4 group was found to be significantly higher than rest of the treated groups except T3. Conclusion: It may be concluded that supplementation of Azolla at 10% of dietary protein requirement along with enzyme supplementation in an isonitrogenous diet showed a better immune response in broilers. PMID:27047208

A Small Molecule Inverse Agonist for the Human Thyroid-Stimulating Hormone Receptor

PubMed Central

Neumann, Susanne; Huang, Wenwei; Eliseeva, Elena; Titus, Steve; Thomas, Craig J.; Gershengorn, Marvin C.

2010-01-01

Small molecule inverse agonists for the TSH receptor (TSHR) may be used as probes of the role of basal (or agonist-independent or constitutive) signaling and may have therapeutic potential as orally active drugs to inhibit basal signaling in patients with thyroid cancer and in some patients with hyperthyroidism. We describe the first small-molecule ligand [1;2-(3-((2,6-dimethylphenoxy)methyl)-4-methoxyphenyl)-3-(furan-2-ylmethyl)-2,3-dihydroquinazolin-4(1H)-one] that exhibits inverse agonist properties at TSHR. 1 inhibits basal and TSH-stimulated signaling, measured as cAMP production, by TSHRs in HEK-EM 293 cells stably expressing wild-type TSHRs; the antagonism of TSH-mediated signaling is competitive. 1 also inhibits basal signaling by wild-type TSHRs, and four constitutively active mutants of TSHR expressed transiently in HEK-EM 293 cells. 1 was active under more physiologically relevant conditions in primary cultures of human thyrocytes expressing endogenous TSHRs where it inhibited basal levels of mRNA transcripts for thyroglobulin, thyroperoxidase, sodium iodide symporter, and TSHR. These data serve as proof of principle that small, drug-like molecules can inhibit basal signaling by TSHR. We suggest that this small molecule is a lead compound for the development of higher-potency inverse agonists that can be used as probes of TSHR biology with therapeutic potential. PMID:20427476

Task-phase-specific dynamics of basal forebrain neuronal ensembles

PubMed Central

Tingley, David; Alexander, Andrew S.; Kolbu, Sean; de Sa, Virginia R.; Chiba, Andrea A.; Nitz, Douglas A.

2014-01-01

Cortically projecting basal forebrain neurons play a critical role in learning and attention, and their degeneration accompanies age-related impairments in cognition. Despite the impressive anatomical and cell-type complexity of this system, currently available data suggest that basal forebrain neurons lack complexity in their response fields, with activity primarily reflecting only macro-level brain states such as sleep and wake, onset of relevant stimuli and/or reward obtainment. The current study examined the spiking activity of basal forebrain neuron populations across multiple phases of a selective attention task, addressing, in particular, the issue of complexity in ensemble firing patterns across time. Clustering techniques applied to the full population revealed a large number of distinct categories of task-phase-specific activity patterns. Unique population firing-rate vectors defined each task phase and most categories of task-phase-specific firing had counterparts with opposing firing patterns. An analogous set of task-phase-specific firing patterns was also observed in a population of posterior parietal cortex neurons. Thus, consistent with the known anatomical complexity, basal forebrain population dynamics are capable of differentially modulating their cortical targets according to the unique sets of environmental stimuli, motor requirements, and cognitive processes associated with different task phases. PMID:25309352

Genetic activation, inactivation and deletion reveal a limited and nuanced role for somatostatin-containing basal forebrain neurons in behavioral state control.

PubMed

Anaclet, Christelle; De Luca, Roberto; Venner, Anne; Malyshevskaya, Olga; Lazarus, Michael; Arrigoni, Elda; Fuller, Patrick M

2018-05-07

Recent studies have identified an especially important role for basal forebrain GABAergic (BF VGAT ) neurons in the regulation of behavioral waking and fast cortical rhythms associated with cognition. However, BF VGAT neurons comprise several neurochemically and anatomically distinct sub-populations, including parvalbumin- and somatostatin-containing BF VGAT neurons (BF Parv and BF SOM ), and it was recently reported that optogenetic activation of BF SOM neurons increases the probability of a wakefulness to non-rapid-eye movement (NREM) sleep transition when stimulated during the animal's rest period. This finding was unexpected given that most BF SOM neurons are not NREM sleep active and that central administration of the synthetic SOM analog, octreotide, suppresses NREM sleep or increases REM sleep. Here we employed a combination of genetically-driven chemogenetic and optogenetic activation, chemogenetic inhibition and ablation approaches to further explore the in vivo role of BF SOM neurons in arousal control. Our findings indicate that acute activation or inhibition of BF SOM neurons is neither wakefulness- nor NREM sleep-promoting, is without significant effect on the EEG, and that chronic loss of these neurons is without effect on total 24h sleep amounts, although a small but significant increase in waking was observed in the lesioned mice during the early active period. Our in vitro cell recordings further reveal electrophysiological heterogeneity in BF SOM neurons, specifically suggesting at least two distinct sub-populations. Taken together our data support the more nuanced view that BF SOM are electrically heterogeneous and are not NREM sleep- or wake-promoting per se , but may exert, in particular during the early active period, a modest inhibitory influence on arousal circuitry. SIGNIFICANCE STATEMENT The cellular basal forebrain (BF) is a highly complex area of the brain that is implicated in a wide-range of higher-level neurobiological processes, including regulating and maintaining normal levels of electrocortical and behavioral arousal. The respective in vivo roles of BF cell populations and their neurotransmitter systems in the regulation of electrocortical and behavioral arousal remains incompletely understood. Here we seek to define the neurobiological contribution of GABAergic somatostanin-containing BF neurons to arousal control. Understanding the respective contribution of BF cell populations to arousal control may provide critical insight into the pathogenesis of a host of neuropsychiatric and neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, schizophrenia and the cognitive impairments of normal aging. Copyright © 2018 the authors.

Effect of acute swim stress on plasma corticosterone and brain monoamine levels in bidirectionally selected DxH recombinant inbred mouse strains differing in fear recall and extinction.

PubMed

Browne, Caroline A; Hanke, Joachim; Rose, Claudia; Walsh, Irene; Foley, Tara; Clarke, Gerard; Schwegler, Herbert; Cryan, John F; Yilmazer-Hanke, Deniz

2014-12-01

Stress-induced changes in plasma corticosterone and central monoamine levels were examined in mouse strains that differ in fear-related behaviors. Two DxH recombinant inbred mouse strains with a DBA/2J background, which were originally bred for a high (H-FSS) and low fear-sensitized acoustic startle reflex (L-FSS), were used. Levels of noradrenaline, dopamine, and serotonin and their metabolites 3,4-dihydroxyphenyacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were studied in the amygdala, hippocampus, medial prefrontal cortex, striatum, hypothalamus and brainstem. H-FSS mice exhibited increased fear levels and a deficit in fear extinction (within-session) in the auditory fear-conditioning test, and depressive-like behavior in the acute forced swim stress test. They had higher tissue noradrenaline and serotonin levels and lower dopamine and serotonin turnover under basal conditions, although they were largely insensitive to stress-induced changes in neurotransmitter metabolism. In contrast, acute swim stress increased monoamine levels but decreased turnover in the less fearful L-FSS mice. L-FSS mice also showed a trend toward higher basal and stress-induced corticosterone levels and an increase in noradrenaline and serotonin in the hypothalamus and brainstem 30 min after stress compared to H-FSS mice. Moreover, the dopaminergic system was activated differentially in the medial prefrontal cortex and striatum of the two strains by acute stress. Thus, H-FSS mice showed increased basal noradrenaline tissue levels compatible with a fear phenotype or chronic stressed condition. Low corticosterone levels and the poor monoamine response to stress in H-FSS mice may point to mechanisms similar to those found in principal fear disorders or post-traumatic stress disorder.

Effect of Acute Swim Stress on Plasma Corticosterone and Brain Monoamine Levels in Bidirectionally Selected DxH Recombinant Inbred Mouse Strains Differing in Fear Recall and Extinction

PubMed Central

Browne, Caroline A.; Hanke, Joachim; Rose, Claudia; Walsh, Irene; Foley, Tara; Clarke, Gerard; Schwegler, Herbert; Cryan, John F.; Yilmazer-Hanke, Deniz

2015-01-01

Stress-induced changes in plasma corticosterone and central monoamine levels were examined in mouse strains that differ in fear-related behaviors. Two DxH recombinant inbred mouse strains with a DBA/2J background, which were originally bred for a high (H-FSS) and low fear-sensitized acoustic startle reflex (L-FSS), were used. Levels of noradrenaline, dopamine, and serotonin and their metabolites (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were studied in the amygdala, hippocampus, medial prefrontal cortex, striatum, hypothalamus, and brainstem. H-FSS mice exhibited increased fear levels and a deficit in fear extinction (within-session) in the auditory fear-conditioning test, and depressive-like behavior in the acute forced swim stress test. They had higher tissue noradrenaline and serotonin levels and lower dopamine and serotonin turnover under basal conditions, although they were largely insensitive to stress-induced changes in neurotransmitter metabolism. In contrast, acute swim stress increased monoamine levels but decreased turnover in the less fearful L-FSS mice. L-FSS mice also showed a trend toward higher basal and stress-induced corticosterone levels and an increase in noradrenaline and serotonin in the hypothalamus and brainstem 30 minutes after stress compared to H-FSS mice. Moreover, the dopaminergic system was activated differentially in the medial prefrontal cortex and striatum of the two strains by acute stress. Thus, H-FSS mice showed increased basal noradrenaline tissue levels compatible with a fear phenotype or chronic stressed condition. Low corticosterone levels and the poor monoamine response to stress in H-FSS mice may point to mechanisms similar to those found in principal fear disorders or posttraumatic stress disorder. PMID:25117886

Plasma Concentration of Prolactin, Testosterone Might Be Associated with Brain Response to Visual Erotic Stimuli in Healthy Heterosexual Males

PubMed Central

Seo, Younghee; Kim, Ji-Woong; Choi, Jeewook

2009-01-01

Objective Many studies have showed that excess or lack of sexual hormones, such as prolactin and testosterone, induced the sexual dysfunction in humans. Little, however, is known about the role of sexual hormones showing normal range in, especially, the basal state unexposed to any sexual stimulation. We hypothesized sexual hormones in the basal state may affect sexual behavior. Methods We investigated the association of the sexual hormones level in the basal hormonal state before visual sexual stimulation with the sexual response-related brain activity during the stimulation. Twelve heterosexual men were recorded the functional MRI signals of their brain activation elicited by passive viewing erotic (ERO), happy-faced (HA) couple, food and nature pictures. Both plasma prolacitn and testosterone concentrations were measured before functional MR scanning. A voxel wise regression analyses were performed to investigate the relationship between the concentration of sexual hormones in basal state and brain activity elicited by ERO minus HA, not food minus nature, contrast. Results The plasma concentration of prolactin in basal state showed positive association with the activity of the brain involving cognitive component of sexual behavior including the left middle frontal gyrus, paracingulate/superior frontal/anterior cingulate gyri, bilateral parietal lobule, right angular, bilateral precuneus and right cerebellum. Testosterone in basal state was positively associated with the brain activity of the bilateral supplementary motor area which related with motivational component of sexual behavior. Conclusion Our results suggested sexual hormones in basal state may have their specific target regions or network associated with sexual response. PMID:20046395

Plasma concentration of prolactin, testosterone might be associated with brain response to visual erotic stimuli in healthy heterosexual males.

PubMed

Seo, Younghee; Jeong, Bumseok; Kim, Ji-Woong; Choi, Jeewook

2009-09-01

Many studies have showed that excess or lack of sexual hormones, such as prolactin and testosterone, induced the sexual dysfunction in humans. Little, however, is known about the role of sexual hormones showing normal range in, especially, the basal state unexposed to any sexual stimulation. We hypothesized sexual hormones in the basal state may affect sexual behavior. We investigated the association of the sexual hormones level in the basal hormonal state before visual sexual stimulation with the sexual response-related brain activity during the stimulation. Twelve heterosexual men were recorded the functional MRI signals of their brain activation elicited by passive viewing erotic (ERO), happy-faced (HA) couple, food and nature pictures. Both plasma prolacitn and testosterone concentrations were measured before functional MR scanning. A voxel wise regression analyses were performed to investigate the relationship between the concentration of sexual hormones in basal state and brain activity elicited by ERO minus HA, not food minus nature, contrast. The plasma concentration of prolactin in basal state showed positive association with the activity of the brain involving cognitive component of sexual behavior including the left middle frontal gyrus, paracingulate/superior frontal/anterior cingulate gyri, bilateral parietal lobule, right angular, bilateral precuneus and right cerebellum. Testosterone in basal state was positively associated with the brain activity of the bilateral supplementary motor area which related with motivational component of sexual behavior. Our results suggested sexual hormones in basal state may have their specific target regions or network associated with sexual response.

Basal Ganglia Dopamine-gamma-Aminobutyric Acid-Acetylcholine Interaction in Organophosphate-Induced Neurotoxicity. Appendices

DTIC Science & Technology

1982-12-01

Animals were maintained ad llbltua on standard laboratory chow and tap water and were housed in a room with automatic 12 hour light and dark cycles and...supernatant fluid was centrl- fuged at 20,000 x g for 20 min to obtain a crude mitochondria ! pellet. The crude mitochondrlal pellet was resuspended...chow and tap water and wer- housed in a room with automatic 12 hour light and dark cycles and temperature set at 25.5 ± 1.8°C. DUsopropylfli’oro

Cytokine production capacity in depression and anxiety.

PubMed

Vogelzangs, N; de Jonge, P; Smit, J H; Bahn, S; Penninx, B W

2016-05-31

Recent studies have suggested that immune function may be dysregulated in persons with depressive and anxiety disorders. Few studies examined the expression of cytokines in response to ex vivo stimulation of blood by lipopolysaccharide (LPS) to study the innate production capacity of cytokines in depression and anxiety. To investigate this, baseline data from the Netherlands Study of Depression and Anxiety (NESDA) were used, including persons (18-65 years; 66% women) with current (that is, past month; N=591) or remitted (N=354) DSM-IV depressive or anxiety disorders and healthy controls (N=297). Depressive and anxiety symptoms were measured by means of the Inventory of Depressive Symptomatology (IDS) and the Beck Anxiety Inventory (BAI). Using Multi-Analyte Profiling technology, plasma levels of 13 cytokines were assayed after whole blood stimulation by addition of LPS. Basal plasma levels of C-reactive protein, interleukin-6 and tumor necrosis factor-α were also available. A basal and a LPS summary index were created. Results show that LPS-stimulated inflammation was associated with increased odds of current depressive/anxiety disorders (odds ratio (OR)=1.28, P=0.009), as was the case for basal inflammation (OR=1.28, P=0.001). These associations were no longer significant after adjustment for lifestyle and health (OR=1.13, P=0.21; OR=1.07, P=0.45, respectively). After adjustment for lifestyle and health, interleukin-8 was associated with both remitted (OR=1.25, P=0.02) and current (OR=1.28, P=0.005) disorders. In addition, LPS-stimulated inflammation was associated with more severe depressive (β=0.129, P<0.001) and anxiety (β=0.165, P<0.001) symptoms, as was basal inflammation. Unlike basal inflammation, LPS-stimulated inflammation was still associated with (anxiety) symptom severity after adjustment for lifestyle and health (IDS: interleukin (IL)-8, MCP-1, MMP2; BAI: LPS index, IL-6, IL-8, IL-10, IL-18, MCP-1, MMP2, TNF-β). To conclude, lifestyle and health factors may partly explain higher levels of basal, as well as LPS-stimulated inflammation in persons with depressive and anxiety disorders. However, production capacity of several cytokines was positively associated with severity of depressive and in particular anxiety symptoms, even while taking lifestyle and health factors into account. Elevated IL-8 production capacity in both previously and currently depressed and anxious persons might indicate a genetic vulnerability for these disorders.

SOX2 and PI3K Cooperate to Induce and Stabilize a Squamous-Committed Stem Cell Injury State during Lung Squamous Cell Carcinoma Pathogenesis

PubMed Central

Kim, Bo Ram; Van de Laar, Emily; Tarumi, Shintaro; Hasenoeder, Stefan; Wang, Dennis; Virtanen, Carl; Bandarchi, Bizhan; Pham, Nhu An; Lee, Sharon; Keshavjee, Shaf; Tsao, Ming-Sound; Moghal, Nadeem

2016-01-01

Although cancers are considered stem cell diseases, mechanisms involving stem cell alterations are poorly understood. Squamous cell carcinoma (SQCC) is the second most common lung cancer, and its pathogenesis appears to hinge on changes in the stem cell behavior of basal cells in the bronchial airways. Basal cells are normally quiescent and differentiate into mucociliary epithelia. Smoking triggers a hyperproliferative response resulting in progressive premalignant epithelial changes ranging from squamous metaplasia to dysplasia. These changes can regress naturally, even with chronic smoking. However, for unknown reasons, dysplasias have higher progression rates than earlier stages. We used primary human tracheobronchial basal cells to investigate how copy number gains in SOX2 and PIK3CA at 3q26-28, which co-occur in dysplasia and are observed in 94% of SQCCs, may promote progression. We find that SOX2 cooperates with PI3K signaling, which is activated by smoking, to initiate the squamous injury response in basal cells. This response involves SOX9 repression, and, accordingly, SOX2 and PI3K signaling levels are high during dysplasia, while SOX9 is not expressed. By contrast, during regeneration of mucociliary epithelia, PI3K signaling is low and basal cells transiently enter a SOX2LoSOX9Hi state, with SOX9 promoting proliferation and preventing squamous differentiation. Transient reduction in SOX2 is necessary for ciliogenesis, although SOX2 expression later rises and drives mucinous differentiation, as SOX9 levels decline. Frequent coamplification of SOX2 and PIK3CA in dysplasia may, thus, promote progression by locking basal cells in a SOX2HiSOX9Lo state with active PI3K signaling, which sustains the squamous injury response while precluding normal mucociliary differentiation. Surprisingly, we find that, although later in invasive carcinoma SOX9 is generally expressed at low levels, its expression is higher in a subset of SQCCs with less squamous identity and worse clinical outcome. We propose that early pathogenesis of most SQCCs involves stabilization of the squamous injury state in stem cells through copy number gains at 3q, with the pro-proliferative activity of SOX9 possibly being exploited in a subset of SQCCs in later stages. PMID:27880766

Inhibition of basal and stimulated release of endothelin-1 from guinea pig tracheal epithelial cells in culture by beta 2-adrenoceptor agonists and cyclic AMP enhancers.

PubMed

Yang, Quan; Battistini, Bruno; Pelletier, Stéphane; Sirois, Pierre

2007-10-01

The effects of cyclic AMP-related compounds and beta adrenoceptor agonists on the basal and lipopolysaccharide (LPS)-stimulated release of endothelin-1 (ET-1) from guinea-pig tracheal epithelial cells (GPTEpCs) in culture were studied. Forskolin (a potent activator of adenylyl cyclase), 8-bromo-cyclic AMP (a cyclic AMP analogue), salbutamol and salmeterol (two beta 2-adrenoceptor agonists), were used to increase cyclic AMP levels. Cultured GPTEpCs released ET-1 continuously over a 24 h incubation period. The values reached 1,938 +/- 122 pg/mg of total cell proteins after 24 h. LPS (10 microg/ml) significantly stimulated the release of ET-1 by 1.6- to 1.8-fold, up to 1,262 +/- 56 pg/mg total cell proteins after an 8 h incubation period. Compound 8-bromo-cyclic AMP (10(-5), 10(-4) and 10(-3) M) reduced the basal release of ET-1 from GPTEpCs by up to 31% (P < 0.01) and the LPS stimulated release by up to 42% (P < 0.05), after an 8 h incubation period. Forskolin (10(-6), 10(-5) and 10(-4) M) also inhibited the basal release of ET-1 by up to 28% (P < 0.05) and LPS-stimulated release of ET-1 by up to 50% (P < 0.05), after an 8 h incubation period. At the concentration of 10(-5) M, forskolin increased cyclic AMP levels in GPTEpCs by 17-fold (P < 0.001) in the medium, 15 min after the beginning of the incubation. Salbutamol (10(-8) to 10(-6) M) had no effect on the basal production and release of ET-1 after 8 h. Conversely, this short acting beta 2-adrenoceptor agonist significantly reduced LPS-mediated increase of ET-1 production by up to 55% (P < 0.05) after an 8 h incubation period. Salmeterol (10(-9) M to 10(-5) M) inhibited basal and LPS-stimulated production and release of ET-1 after an 8 h incubation period (between 44 and 51%, P < 0.01). Both salbutamol and salmeterol (10(-6) M) increase cyclic AMP levels by five- and twofold, respectively (P < 0.05). In summary, these observations indicate that beta 2-adrenoceptor agonists or cyclic AMP enhancers can modulate both basal and more markedly, the enhanced production of ET-1 from LPS-activated guinea pig airway EpCs. In addition, these compounds increase cyclic AMP levels in the cells. It is suggested that there is a correlation between cyclic AMP increase and inhibition of ET-1 release by guinea pig airway EpCs. Since ET-1 production was shown to be elevated in asthmatic subjects and in patients suffering from other inflammatory lung disorders, the inhibition of its production by beta adrenoceptor agonists, such as salbutamol and salmeterol, could be added to their therapeutical benefits.

A Novel mouse model of enhanced proteostasis: Full-length human heat shock factor 1 transgenic mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pierce, Anson, E-mail: piercea2@uthscsa.edu; Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, 78229; The Department of Veteran's Affairs, South Texas Veterans Health Care System, San Antonio, Texas, 78284

2010-11-05

Research highlights: {yields} Development of mouse overexpressing native human HSF1 in all tissues including CNS. {yields} HSF1 overexpression enhances heat shock response at whole-animal and cellular level. {yields} HSF1 overexpression protects from polyglutamine toxicity and favors aggresomes. {yields} HSF1 overexpression enhances proteostasis at the whole-animal and cellular level. -- Abstract: The heat shock response (HSR) is controlled by the master transcriptional regulator heat shock factor 1 (HSF1). HSF1 maintains proteostasis and resistance to stress through production of heat shock proteins (HSPs). No transgenic model exists that overexpresses HSF1 in tissues of the central nervous system (CNS). We generated a transgenicmore » mouse overexpressing full-length non-mutant HSF1 and observed a 2-4-fold increase in HSF1 mRNA and protein expression in all tissues studied of HSF1 transgenic (HSF1{sup +/0}) mice compared to wild type (WT) littermates, including several regions of the CNS. Basal expression of HSP70 and 90 showed only mild tissue-specific changes; however, in response to forced exercise, the skeletal muscle HSR was more elevated in HSF1{sup +/0} mice compared to WT littermates and in fibroblasts following heat shock, as indicated by levels of inducible HSP70 mRNA and protein. HSF1{sup +/0} cells elicited a significantly more robust HSR in response to expression of the 82 repeat polyglutamine-YFP fusion construct (Q82YFP) and maintained proteasome-dependent processing of Q82YFP compared to WT fibroblasts. Overexpression of HSF1 was associated with fewer, but larger Q82YFP aggregates resembling aggresomes in HSF1{sup +/0} cells, and increased viability. Therefore, our data demonstrate that tissues and cells from mice overexpressing full-length non-mutant HSF1 exhibit enhanced proteostasis.« less

Effect of basal forebrain stimulation on extracellular acetylcholine release and blood flow in the olfactory bulb.

PubMed

Uchida, Sae; Kagitani, Fusako

2017-05-12

The olfactory bulb receives cholinergic basal forebrain input, as does the neocortex; however, the in vivo physiological functions regarding the release of extracellular acetylcholine and regulation of regional blood flow in the olfactory bulb are unclear. We used in vivo microdialysis to measure the extracellular acetylcholine levels in the olfactory bulb of urethane-anesthetized rats. Focal chemical stimulation by microinjection of L-glutamate into the horizontal limb of the diagonal band of Broca (HDB) in the basal forebrain, which is the main source of cholinergic input to the olfactory bulb, increased extracellular acetylcholine release in the ipsilateral olfactory bulb. When the regional cerebral blood flow was measured using laser speckle contrast imaging, the focal chemical stimulation of the HDB did not significantly alter the blood flow in the olfactory bulb, while increases were observed in the neocortex. Our results suggest a functional difference between the olfactory bulb and neocortex regarding cerebral blood flow regulation through the release of acetylcholine by cholinergic basal forebrain input.

Presence of negative charge on the basal planes of New York talc.

PubMed

Burdukova, E; Becker, M; Bradshaw, D J; Laskowski, J S

2007-11-01

Potentiometric titration measurements as well as rheological measurements of talc aqueous suspensions indicate that the behavior of the New York talc particles is consistent with the presence of a negative charge on their basal planes. The possibility of the presence of a negative electrical charge on the basal planes of talc particles is analyzed in this paper. Samples of New York talc were studied using electron microprobe analysis and dehydration techniques and the exact chemical formula of New York talc was determined. It was found that there exists a deficiency of protons in the tetrahedral layers of talc, resulting from substitution of Si(4+) ions with Al(3+) and Ti(3+) ions. The comparison of the level of substitution of Si(4+) ions with ions of a lower valency was found to be of a similar order of magnitude as that found in other talc deposits. This strongly points to the presence of a negative charge on the talc basal planes.

Correlations of hair level with salivary level in cortisol and cortisone.

PubMed

Zhang, Quan; Chen, Zheng; Chen, Shenghuo; Yu, Tian; Wang, Juxia; Wang, Weiwen; Deng, Huihua

2018-01-15

Contrary findings exist on the consistency between hair cortisol and salivary cortisol in assessing the basal activity of the hypothalamic-pituitary-adrenal (HPA) axis. The mismatches in temporal characteristic and the indices of hair and salivary cortisol might be potential reasons for the inconsistency. The aim of this study was to investigate the consistency between hair and salivary levels in cortisol and cortisone by directly examining the correlation between hair level and salivary level with different temporal characteristics (acute, short-term and long-term levels) and reflecting different HPA functions (basal level and reactivity level) in the well-matched time span. A longitudinal design within a five-week period was conducted in a sample of 44 healthy female college students (mean age: 18.8yrs.; age range: 18-22yrs) of Han nationality with the exclusion criteria, such as use of oral contraceptives or glucocorticoids and bleached hairs, etc. Four saliva samples (awakening, awakening+30min, awakening+4h and awakening+9h) were collected from an identical participant on three separate days with an interval of one week and 1-cm hair segment nearest to the scalp was collected two weeks later after completing saliva collection. Cortisol and cortisone in saliva and hair were simultaneously measured with high performance liquid chromatography tandem mass spectrometry. There were significantly moderate correlations in cortisol and cortisone between hair level and three-day average of single-day salivary level, but low to moderate correlations between hair level and single-point and single-day salivary level. Hair cortisol and cortisone were unrelated to single-day level and three-day average of diurnal slope and cortisol awakening response of salivary cortisol and cortisone, respectively. The considerable consistency between hair level and long-term salivary level in cortisol and cortisone implies that cortisol and cortisone in hair are valid biomarkers of cumulative exposure of cortisol and cortisone to retrospectively reflect long-term basal activity of the HPA system. Copyright © 2017 Elsevier Inc. All rights reserved.

Neuroprotection and aging of the cholinergic system: a role for the ergoline derivative nicergoline (Sermion).

PubMed

Giardino, L; Giuliani, A; Battaglia, A; Carfagna, N; Aloe, L; Calza', L

2002-01-01

The aging brain is characterized by selective neurochemical changes involving several neural populations. A deficit in the cholinergic system of the basal forebrain is thought to contribute to the development of cognitive symptoms of dementia. Attempts to prevent age-associated cholinergic vulnerability and deterioration therefore represent a crucial point for pharmacotherapy in the elderly. In this paper we provide evidence for the protective effect of nicergoline (Sermion) on the degeneration of cholinergic neurons induced by nerve growth factor deprivation. Nerve growth factor deprivation was induced by colchicine administration in rats 13 and 18 months old. Colchicine induces a rapid and substantial down-regulation of choline acetyltransferase messenger RNA level in the basal forebrain in untreated adult, middle-aged and old rats. Colchicine failed to cause these effects in old rats treated for 120 days with nicergoline 10 mg/kg/day, orally. Moreover, a concomitant increase of both nerve growth factor and brain-derived neurotrophic factor content was measured in the basal forebrain of old, nicergoline-treated rats. Additionally, the level of messenger RNA for the brain isoform of nitric oxide synthase in neurons of the basal forebrain was also increased in these animals. Based on the present findings, nicergoline proved to be an effective drug for preventing neuronal vulnerability due to experimentally induced nerve growth factor deprivation.

The diagnosis of nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, based on serum basal or post-ACTH stimulation 17-hydroxyprogesterone, can lead to false-positive diagnosis.

PubMed

Ambroziak, Urszula; Kępczyńska-Nyk, Anna; Kuryłowicz, Alina; Małunowicz, Ewa Maria; Wójcicka, Anna; Miśkiewicz, Piotr; Macech, Magdalena

2016-01-01

As nonclassic congenital adrenal hyperplasia (NCCAH) needs to be taken into account in women with hyperandrogenism, we aimed to assess whether the recommended level of poststimulated 17OHP ≥30 nmol/l confirms NCCAH. Forty, consecutive women with biochemical and/or clinical hyperandrogenism (aged 25·4, 18-38) suspected of having NCCAH were recruited to the study. In patients with 17OHP level between 5·1 and 29·9 nmol/l an ACTH stimulation test was performed. In patients with basal or poststimulated 17OHP ≥30 nmol/l, twenty-four-hour urinary steroid profile (USP) analysis was performed and CYP21A2 mutation was assessed. In selected patients with poststimulated 17OHP <30 nmol/l USP was also performed. The group was divided into two subgroups with basal or poststimulated 17OHP ≥30 nmol/l (group A) and with poststimulated 17OHP <30 nmol/l (group B). Among 40 patients, basal or poststimulated 17OHP ≥30 nmol/l was found in 21, but NCCAH was confirmed by USP followed by genetic testing only in 5 (24%). Four patients were diagnosed as heterozygotes, and in twelve, no CYP21A2 mutation was detected. The diagnosis of NCCAH based only on serum 17OHP measurements (basal or poststimulated) may lead to false-positive diagnosis when performed by immunoassay with a cut-off value of ≥30 nmol/l. The definitive diagnosis can be established based on USP and/or genetic testing. © 2015 John Wiley & Sons Ltd.

Preliminary evidence that acute stress moderates basal testosterone's association with retaliatory behavior.

PubMed

Prasad, Smrithi; Narayanan, Jayanth; Lim, Vivien K G; Koh, Gerald C H; Koh, David S Q; Mehta, Pranjal H

2017-06-01

A contribution to a special issue on Hormones and Human Competition. Testosterone is theorized to increase retaliation after social provocation. However, empirical evidence in support of these theories is mixed. The present research investigated whether acute stress causally suppresses testosterone's association with retaliation. We also explored sex differences in behavioral responses to acute stress. Thirty-nine participants (51.28% male) were randomly assigned to a high- or low-stress condition. Then participants engaged in 20 one-shot rounds of the ultimatum game, which was used to assess retaliatory behavioral responses to unfair treatment. Participants provided two saliva samples to measure testosterone and cortisol concentrations - one sample before the stress manipulation, and the second after the ultimatum game (20minutes post-stressor). Results revealed a positive association between basal testosterone and retaliation in the low-stress condition, but not in the high-stress condition. Further, cortisol concentrations increased in the high- compared to the low-stress condition, and these cortisol changes moderated the association between basal testosterone and retaliation. The associations between basal testosterone and retaliation under varying levels of stress were similar in men and women. However, there was a sex difference in behavioral responses to the stress manipulation that was independent of testosterone. In women, the high-stress condition reduced retaliation compared to the low-stress condition, whereas in men the opposite pattern emerged. Collectively, this study (i) provides preliminary evidence that experimentally manipulated stress blocks basal testosterone's association with retaliation, and (ii) reveals a sex difference in retaliation under varying levels of stress. Discussion focuses on mechanisms, limitations, and the need for follow-up studies with larger sample sizes. Copyright © 2016 Elsevier Inc. All rights reserved.

Basal expression of insulin-like growth factor 1 receptor determines intrinsic resistance of cancer cells to a phosphatidylinositol 3-kinase inhibitor ZSTK474

PubMed Central

Isoyama, Sho; Kajiwara, Gensei; Tamaki, Naomi; Okamura, Mutsumi; Yoshimi, Hisashi; Nakamura, Naoki; Kawamura, Kento; Nishimura, Yumiko; Namatame, Nachi; Yamori, Takao; Dan, Shingo

2015-01-01

Drug resistance often critically limits the efficacy of molecular targeted drugs. Although pharmacological inhibition of phosphatidylinositol 3-kinase (PI3K) is an attractive therapeutic strategy for cancer therapy, molecular determinants for efficacy of PI3K inhibitors (PI3Kis) remain unclear. We previously identified that overexpression of insulin-like growth factor 1 receptor (IGF1R) contributed to the development of drug resistance after long-term exposure to PI3Kis. In this study, we examined the involvement of basal IGF1R expression in intrinsic resistance of drug-naïve cancer cells to PI3Kis and whether inhibition of IGF1R overcomes the resistance. We found that cancer cells highly expressing IGF1R showed resistance to dephosphorylation of Akt and subsequent antitumor effect by ZSTK474 treatment. Knockdown of IGF1R by siRNAs facilitated the dephosphorylation and enhanced the drug efficacy. These cells expressed tyrosine-phosphorylated insulin receptor substrate 1 at high levels, which was dependent on basal IGF1R expression. In these cells, the efficacy of ZSTK474 in vitro and in vivo was improved by its combination with the IGF1R inhibitor OSI-906. Finally, we found a significant correlation between the basal expression level of IGF1R and the inefficacy of ZSTK474 in an in vivo human cancer panel, as well as in vitro. These results suggest that basal IGF1R expression affects intrinsic resistance of cancer cells to ZSTK474, and IGF1R is a promising target to improve the therapeutic efficacy. The current results provide evidence of combination therapy of PI3Kis with IGF1R inhibitors for treating IGF1R-positive human cancers. PMID:25483727

Importance of serum basal tryptase levels in children with insect venom allergy.

PubMed

Yavuz, S T; Sackesen, C; Sahiner, U M; Buyuktiryaki, B; Arik Yilmaz, E; Sekerel, B E; Soyer, O U; Tuncer, A

2013-03-01

The importance of serum basal tryptase (sBT) levels on patients with venom allergy is highlighted in recent adulthood studies. The aim of this study was to evaluate the sBT levels of venom-allergic children with varying severity of clinical reactions. We also aimed to document the association between sBT levels and severe systemic reactions (SR). Serum basal tryptase levels were estimated by UniCAP (Pharmacia & Upjohn, Uppsala, Sweden). Children who suffered from large local reaction (LLR) or SR after insect stings were included along with healthy control subjects without a history of any local or SR after insect stings. A total of 128 children (55 with SR, 18 with LLR, and 55 age and sex-matched control subjects) with a median age of 8.9 years (range 3.2-17.4) were enrolled. Severe SR was encountered in 24 (44%) patients with SRs. The median level of sBT in children with SRs (median, interquartile range) [4.2 μg/l (3.6-4.9)] was significantly higher than in children with LLRs [3.1 μg/l (2.5-4.0)] and healthy control subjects [2.9 μg/l (2.3-3.4)] (P < 0.001). Logistic regression analysis revealed sBT ≥ 4.8 μg/l as a significant risk factor for severe SR (5.7 [1.5-21.4]; P = 0.01) in children with venom allergy. Our results indicate that sBT levels are associated with a higher risk of severe SR in children with insect venom hypersensitivity. Determination of sBT levels may help clinicians to identify patients under risk of severe SRs and optimal and timely use of therapeutic interventions in children with venom allergy. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Regulatory peptides in the plasma of patients with chronic cardiac failure at rest and during exercise.

PubMed

Nicholls, D P; Riley, M; Elborn, J S; Stanford, C F; Shaw, C; McKillop, J M; Buchanan, K D

1992-10-01

The levels of several regulatory peptides were measured in peripheral plasma samples from individuals with chronic cardiac failure (CCF) and matched controls in both the resting state and during a short period of maximal exercise. Basal levels of noradrenaline (NA; 705 +/- 114 vs 195 +/- 54 ng.l-1; mean +/- SEM; P < 0.05), plasma renin activity (PRA; 12.9 +/- 2.9 vs 2.1 +/- 0.3 ng AI ml-1.h-1; P < 0.05) and aldosterone (ALDO; 325 +/- 49 vs 87 +/- 8 ng.l-1; P < 0.05) were all raised in the patients with CCF, and increased further with exercise. Basal circulating levels of atrial natriuretic peptide (ANP) were also significantly higher in the CCF group compared to controls (136 +/- 35 vs 27 +/- 5 ng.l-1; P < 0.01), but the response to exercise was attenuated, so that at peak exercise, no significant difference was observed. Basal circulating levels of gastrin-releasing peptide (GRP) (29 +/- 4 vs 40 +/- 4 ng.l-1; P < 0.05) and secretin (13 +/- 1 vs 32 +/- 4 ng.l-1; P < 0.05) were significantly lower in the CCF group when compared to controls and there was no significant change in the levels of either peptide with exercise. Levels of neurokinin A (NKA), neuropeptide Y (NPY) and neurotensin (NT) were somewhat higher in patients, but the differences were not significant, and there were no changes during exercise. There were also no significant differences in the levels of vasoactive intestinal peptide (VIP), glucose-dependent insulinotropic polypeptide (GIP), insulin or glucagon in either experimental group both before and during exercise. We have therefore identified different circulating levels of certain regulatory peptides in patients with CCF, but the significance of these remains unclear.

Fetal programming of adrenal androgen excess: lessons from a nonhuman primate model of polycystic ovary syndrome.

PubMed

Abbott, David H; Zhou, Rao; Bird, Ian M; Dumesic, Daniel A; Conley, Alan J

2008-01-01

Adrenal androgen excess is found in adult female rhesus monkeys previously exposed to androgen treatment during early gestation. In adulthood, such prenatally androgenized female monkeys exhibit elevated basal circulating levels of dehydroepiandrosterone sulfate (DHEAS), typical of polycystic ovary syndrome (PCOS) women with adrenal androgen excess. Further androgen and glucocorticoid abnormalities in PA female monkeys are revealed by acute ACTH stimulation: DHEA, androstenedione and corticosterone responses are all elevated compared to responses in controls. Pioglitazone treatment, however, diminishes circulating DHEAS responses to ACTH in both prenatally androgenized and control female monkeys, while increasing the 17-hydroxyprogesterone response and reducing the DHEA to 17-hydroxyprogesterone ratio. Since 60-min post-ACTH serum values for 17-hydroxyprogesterone correlate negatively with basal serum insulin levels (all female monkeys on pioglitazone and placebo treatment combined), while similar DHEAS values correlate positively with basal serum insulin levels, circulating insulin levels may preferentially support adrenal androgen biosynthesis in both prenatally androgenized and control female rhesus monkeys. Overall, our findings suggest that differentiation of the monkey adrenal cortex in a hyperandrogenic fetal environment may permanently upregulate adult adrenal androgen biosynthesis through specific elevation of 17,20-lyase activity in the zona fasciculata-reticularis. As adult prenatally androgenized female rhesus monkeys closely emulate PCOS-like symptoms, excess fetal androgen programming may contribute to adult adrenal androgen excess in women with PCOS.

Fetal programming of adrenal androgen excess: lessons from a nonhuman primate model of polycystic ovary syndrome

PubMed Central

Abbott, David H; Zhou, Rao; Bird, Ian M; Dumesic, Daniel A; Conley, Alan J

2008-01-01

Adrenal androgen excess is found in adult female rhesus monkeys previously exposed to androgen treatment during early gestation. In adulthood, such prenatally androgenized female monkeys exhibit elevated basal circulating levels of DHEAS, typical of PCOS women with adrenal androgen excess. Further androgen and glucocorticoid abnormalities in PA female monkeys are revealed by acute ACTH stimulation: DHEA, androstenedione and corticosterone responses are all elevated compared to responses in controls. Pioglitazone treatment, however, diminishes circulating DHEAS responses to ACTH in both prenatally androgenized and control female monkeys, while increasing the 17-hydroxyprogesterone response and reducing the DHEA to 17-hydroxyprogesterone ratio. Since 60-min post-ACTH serum values for 17-hydroxyprogesterone correlate negatively with basal serum insulin levels (all female monkeys on pioglitazone and placebo treatment combined), while similar DHEAS values correlate positively with basal serum insulin levels, circulating insulin levels may preferentially support adrenal androgen biosynthesis in both prenatally androgenized and control female rhesus monkeys. Overall, our findings suggest that differentiation of the monkey adrenal cortex in a hyperandrogenic fetal environment may permanently upregulate adult adrenal androgen biosynthesis through specific elevation of 17,20-lyase activity in the zona fasciculata-reticularis. As adult prenatally androgenized female rhesus monkeys closely emulate PCOS-like symptoms, excess fetal androgen programming may contribute to adult adrenal androgen excess in women with PCOS. PMID:18493139

Effects of the tricothecene mycotoxin diacetoxyscirpenol on egg production of broiler breeders.

PubMed

Brake, J; Hamilton, P B; Kittrell, R S

2002-12-01

Three experiments were conducted to determine the effects of 4,15-diacetoxyscirpenol (DAS) on egg quality and egg production of broiler breeders. In Experiment 1, feed containing 0, 1.25, 2.5, or 5.0 mg DAS/ kg was fed from 67 to 69 wk of age followed by a 3-wk recovery period on a slat-litter floor. In Experiment 2, individually caged broiler breeder females were studied from 23 to 31 wk of age. The basal diet containing 0, 5, 10, or 20 mg DAS/kg was fed from 25 to 27 wk of age. In Experiment 3, individually caged broiler breeder hens were studied from 23 to 32 wk of age. DAS was fed at levels of 0 (basal), 5, 10, and 20 mg DAS/kg for 2 wk beginning at Week 24, followed by the basal breeder diet for 7 wk. Egg production was not affected by levels of up to 5 mg DAS/kg in the older hens of Experiment 1. When fed from 25 to 27 wk of age in Experiment 2, DAS decreased egg production at the 20 mg/kg level only. When fed from 24 to 25 wk of age in Experiment 3, DAS had no significant effect on egg production or egg quality. Short-term consumption of DAS at levels that might naturally occur appears to have little effect on broiler breeder egg production.

Hepatoprotective effects of parsley, basil, and chicory aqueous extracts against dexamethasone-induced in experimental rats

PubMed Central

Soliman, Hanan A.; El-Desouky, Mohamed A.; Hozayen, Walaa G.; Ahmed, Rasha R.; Khaliefa, Amal K.

2016-01-01

Aim: The objective of this study is to investigate the hypoglycemic, hypolipidemic, and hepatoprotective effects of the aqueous extract of parsley, basil, and chicory whole plant in normal and dexamethasone (Dex) rats. Materials and Methods: 50 female albino rats were used in this study and divided into 5 groups (for each 10). Group (1) fed basal diet and maintained as negative control group. Group (2) received Dex in a dose of (0.1 mg/kg b. wt.). Groups 3, 4, and 5 were treated with Dex along with three different plant extracts of parsley, basil, and chicory (2 g/kg b. wt.), (400 mg/kg b. wt.), and (100 mg/kg b. wt.), respectively. Results: All these groups were treated given three times per week for 8 consecutive weeks. Dex-induced alterations in the levels of serum glucose, triglyceride, cholesterol, low-density lipoprotein-cholesterol levels and cardiovascular indices and serum alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities, liver thiobarbituric acid (TBARS) levels increased, while high-density lipoprotein-cholesterol, total protein, albumin, and liver glutathione (GSH) levels decreased. On the other hand, plant extracts succeeded to modulate these observed abnormalities resulting from Dex as indicated by the reduction of glucose, cholesterol, TBARS, and the pronounced improvement of the investigated biochemical and antioxidant parameters. Conclusions: It was concluded that probably, due to its antioxidant property, parsley, basil, and chicory extracts have hepatoprotective effects in Dex-induced in rats. PMID:27069727