scholarly journals Evolution of hominin detoxification: Neanderthal and modern human AHR respond similarly to TCDD

2018 ◽  
Author(s):  
Jac M.M.J.G. Aarts ◽  
Gerrit M. Alink ◽  
Henk J. Franssen ◽  
Wil Roebroeks
Keyword(s):  
Codon Usage ◽  
Cultured Cells ◽  
Modern Human ◽  
Cytochrome P450 1A1 ◽  
Coding Region ◽  
Modern Humans ◽  
Response Curves ◽  
Aromatic Hydrocarbon Receptor ◽  
Significant Difference

ABSTRACTIn studies of hominin adaptations to fire use, the role of the aromatic hydrocarbon receptor (AHR) in the evolution of hominin detoxification, especially regarding toxic smoke components, has been highlighted, including statements that the modern human AHR is significantly better at dealing with smoke toxins. We compared the AHR-controlled induction of cytochrome P450 1A1 (CYP1A1) in cultured cells transfected with an Altai-Neanderthal respectively a modern human reference AHR expression construct, and exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We compared the complete AHR mRNA sequences including the untranslated regions (UTRs), maintaining the original codon usage, in HeLa human cervix epithelial adenocarcinoma cells. Our experiments complement a previous study of the AHR coding region optimized for mammalian codon usage and expressed in rat cells. Our results show no significant difference in CYP1A1 induction by TCDD between Neanderthal and modern human AHR (instead of a previously reported 150-1000 times difference range before), demonstrating that expression in a homologous cellular background is of major importance. The two dose-response curves almost coincide, except for a higher extrapolated maximum induction level for the Neanderthal AHR, possibly caused by a 5’-UTR G-variant known from modern humans (rs7796976). Our results are strongly at odds with a major role of the modern human AHR in the evolution of hominin detoxification of smoke components and consistent with our previous study which concluded that efficient detoxification alleles are more dominant in ancient hominins than in modern humans based on 18 relevant genes in addition to AHR.

scholarly journals Evolution of Hominin Detoxification: Neanderthal and Modern Human Ah Receptor Respond Similarly to TCDD

2020 ◽  
Author(s):  
Jac M M J G Aarts ◽  
Gerrit M Alink ◽  
Henk J Franssen ◽  
Wil Roebroeks
Keyword(s):  
Codon Usage ◽  
Modern Human ◽  
Ah Receptor ◽  
Coding Region ◽  
Modern Humans ◽  
Protein Activity ◽  
Response Curves ◽  
Human Dose ◽  
Significant Difference

Abstract In studies of hominin adaptations to fire use, the role of the aryl hydrocarbon receptor (AHR) in the evolution of detoxification has been highlighted, including statements that the modern human AHR confers a significantly better capacity to deal with toxic smoke components than the Neanderthal AHR. To evaluate this, we compared the AHR-controlled induction of cytochrome P4501A1 (CYP1A1) mRNA in HeLa human cervix epithelial adenocarcinoma cells transfected with an Altai-Neanderthal or a modern human reference AHR expression construct, and exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We compared the complete AHR mRNA sequences including the untranslated regions (UTRs), maintaining the original codon usage. We observe no significant difference in CYP1A1 induction by TCDD between Neanderthal and modern human AHR, whereas a 150–1,000 times difference was previously reported in a study of the AHR coding region optimized for mammalian codon usage and expressed in rat cells. Our study exemplifies that expression in a homologous cellular background is of major importance to determine (ancient) protein activity. The Neanderthal and modern human dose–response curves almost coincide, except for a slightly higher extrapolated maximum for the Neanderthal AHR, possibly caused by a 5′-UTR G-variant known from modern humans (rs7796976). Our results are strongly at odds with a major role of the modern human AHR in the evolution of hominin detoxification of smoke components and consistent with our previous study based on 18 relevant genes in addition to AHR, which concluded that efficient detoxification alleles are more dominant in ancient hominins, chimpanzees, and gorillas than in modern humans.

scholarly journals Is Response to Genotoxic Stress Similar in Populations of African and European Ancestry? A Study of Dose-Response After in vitro Irradiation

2021 ◽  
Vol 12 ◽  
Author(s):  
Mamadou Soumboundou ◽  
Julien Dossou ◽  
Yossef Kalaga ◽  
Innocent Nkengurutse ◽  
Ibrahima Faye ◽  
...  
Keyword(s):  
Chromosomal Aberrations ◽  
Dose Response ◽  
Genotoxic Stress ◽  
European Ancestry ◽  
Response Curves ◽  
Blood Samples ◽  
Dicentric Chromosomes ◽  
Significant Difference ◽  
Dose Response Curves

Background: Exposure to genotoxic stress such as radiation is an important public health issue affecting a large population. The necessity of analyzing cytogenetic effects of such exposure is related to the need to estimate the associated risk. Cytogenetic biological dosimetry is based on the relationship between the absorbed dose and the frequency of scored chromosomal aberrations. The influence of confounding factors on radiation response is a topical issue. The role of ethnicity is unclear. Here, we compared the dose-response curves obtained after irradiation of circulating lymphocytes from healthy donors of African and European ancestry.Materials and Methods: Blood samples from six Africans living in Africa, five Africans living in Europe, and five Caucasians living in Europe were exposed to various doses (0–4 Gy) of X-rays at a dose-rate of 0.1 Gy/min using an X-RAD320 irradiator. A validated cohort composed of 14 healthy Africans living in three African countries was included and blood samples were irradiated using the same protocols. Blood lymphocytes were cultured for 48 h and chromosomal aberrations scored during the first mitosis by telomere and centromere staining. The distribution of dicentric chromosomes was determined and the Kruskal-Wallis test was used to compare the dose-response curves of the two populations.Results: No spontaneous dicentric chromosomes were detected in African donors, thus establishing a very low background of unstable chromosomal aberrations relative to the European population. There was a significant difference in the dose response curves between native African and European donors. At 4 Gy, African donors showed a significantly lower frequency of dicentric chromosomes (p = 8.65 10–17), centric rings (p = 4.0310–14), and resulting double-strand-breaks (DSB) (p = 1.32 10–18) than European donors. In addition, a significant difference was found between African donors living in Europe and Africans living in Africa.Conclusion: This is the first study to demonstrate the important role of ethnic and environmental factors that may epigenetically influence the response to irradiation. It will be necessary to establish country-of-origen-specific dose response curves to practice precise and adequate biological dosimetry. This work opens new perspective for the comparison of treatments based on genotoxic agents, such as irradiation.

scholarly journals Moderate hypothermia attenuates α1-adrenoceptor-mediated contraction in human varicose spermatic vein: The role of nitric oxide(Short communication)

2016 ◽  
Vol 103 (4) ◽  
pp. 481-486 ◽  
Author(s):  
KE Nurullahoglu-Atalik ◽  
A Cenker
Keyword(s):  
Nitric Oxide ◽  
Short Communication ◽  
Spermatic Vein ◽  
Moderate Hypothermia ◽  
Response Curves ◽  
Adrenoceptor Agonist ◽  
Significant Difference ◽  
Endothelial Nitric Oxide ◽  
Higher Sensitivity

The effects of moderate hypothermia (28 °C) on the response of human varicose spermatic vein to α1-adrenoceptor agonist phenylephrine and the role of endothelial nitric oxide (NO) in these effects were studied. Concentration–response curves for phenylephrine (10−9 to 3 × 10−4 M) were recorded in rings with and without endothelium at 37 and 28 °C. To further analyze the role of NO, in the response to phenylephrine during hypothermia, the effects of this agonist in the presence of NG-nitro-L-arginine methyl ester (10−4 M) were also determined. Under every condition tested, phenylephrine produced a marked, concentration-dependent contraction. Sensitivity of intact veins to the agonist was consistently lower at 28 °C than at 37 °C. There was no significant difference in phenylephrine response at 28 and 37 °C in vessels without endothelium but at 28 °C veins without endothelium showed a higher sensitivity than intact veins to phenylephrine. The sensitivity of veins with and without endothelium to nitroprusside (10−9 to 3 × 10−3 M) was significantly decreased during hypothermia, and endothelium removal did not affect the relaxation to this nitrovasodilator. These results suggest that moderate hypothermia decreases the sensitivity of human varicose spermatic vein to phenylephrine probably by increasing the availability of endothelial NO.

Role of Teachers in Building the Concept of Sustainable Development: Success or Failure

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Ayaz Muhammad Khan ◽  
Amber Jamshaid ◽  
Tayyibah Roohi ◽  
Amna Ramzan
Keyword(s):  
Sustainable Development ◽  
Primary School ◽  
Sampling Technique ◽  
School Teachers ◽  
Primary School Teachers ◽  
Primary Level ◽  
Significant Difference ◽  
Role Of Teachers ◽  
Major Factors

Sustainable Development (SD) is a rich, challenging and thought-provoking construct in social sciences. The main purpose of this paper was to identify and explore the role played by primary school teachers in building up the idea of sustainable development (SD) among students. This paper was intended to identify that how a teacher can successfully execute the concept of SD by influencing students’ minds at the primary level. Quantitative survey technique were utilized for data collection. All the primary school teachers of Lahore division comprised the population of the study. Through multistage sampling technique, 352 primary school teachers were selected as participants of the study. A self-developed SD questionnaire incorporating four major factors (teachers’ awareness, pedagogy, curricular and co-curricular activities) with Cronbach’s alpha value = .93 was used to measure the role of teachers in building the sustainability concept among students at primary level. The results indicated a significant mean score difference among SD scores of teachers, sector wise (private and public). Furthermore, the results also reconnoitered the significant difference (p=.04) between the mean scores of female and male teachers in building up the SD concept in students’ minds.

OVARIAN ASCORBIC ACID DEPLETION TEST FOR LUTEINIZING HORMONE

1967 ◽  
Vol 56 (4) ◽  
pp. 619-625 ◽  
Author(s):  
Hans Jacob Koed ◽  
Christian Hamburger
Keyword(s):  
Ascorbic Acid ◽  
Luteinizing Hormone ◽  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Human Origin ◽  
Response Curves ◽  
Significant Difference ◽  
The Mean ◽  
Different Levels

ABSTRACT Comparison of the dose-response curves for LH of ovine origin (NIH-LH-S8) and of human origin (IRP-HMG-2) using the OAAD test showed a small, though statistically significant difference, the dose-response curve for LH of human origin being a little flatter. Two standard curves for ovine LH obtained with 14 months' interval, were parallel but at different levels of ovarian ascorbic acid. When the mean ascorbic acid depletions were calculated as percentages of the control levels, the two curves for NIH-LH-S8 were identical. The use of standards of human origin in the OAAD test for LH activity of human preparations is recommended.

STUDIES ON SULFATION FACTOR (SF) ACTIVITY OF HUMAN SERUM

1960 ◽  
Vol XXXV (III) ◽  
pp. 381-396 ◽  
Author(s):  
Sven Almqvist
Keyword(s):  
Human Serum ◽  
Normal Serum ◽  
Treatment Level ◽  
Response Curves ◽  
Normal Children ◽  
Significant Difference ◽  
Human Sera ◽  
Normal Humans ◽  
Pre Treatment ◽  
Dose Levels

ABSTRACT The sulfation factor (SF) activity of human sera has been estimated using a modification of the method of Daughaday et al. (1959). Each assay was statistically evaluated. The method had a mean precision of 0.14 and, used as an assay of GH of human serum, a sensitivity in three pituitary dwarfs of 0.1 to 0.6 μg of HGH/ml of serum. SF activity was found at all ages between 1 month and 75 years. There was a significantly lower mean SF activity below the age of half a year. Three cases of pituitary dwarfism had significantly low SF activities of sera. There was no significant difference between the SF activities of sera from untreated pituitary dwarfs and the sera from normal children below half a year of age. Dose-response curves with large volumes of sera from pituitary dwarfs and small volumes of sera from normal humans had the same slopes. Four mg of HGH prepared according to the method of Li & Papkoff (1956) resulted in a normal serum SF activity in each of the three dwarfs. A significant (P < 0.01) linear relationship was found between the concentration of SF activity of sera from these subjects and the logarithm of the dose of HGH given with dose levels of 1, 2 and 4 mg daily for three days. The decline of serum SF activity to the pre-treatment level following HGH in one dwarf suggested a half life not different from that indicated by others for growth hormone.

Effectiveness Of Toilet Training Education On Mother's Behavior And Toddler Age Toilet Training Ability (18-36 Months)

2020 ◽  
Vol 5 (2) ◽  
pp. 49-55
Author(s):  
Hafiko Andresni ◽  
Zahtamal Zahtamal ◽  
Winda Septiani ◽  
Mitra Mitra ◽  
Lita Lita
Keyword(s):  
Sampling Technique ◽  
T Test ◽  
The Body ◽  
Toilet Training ◽  
Wilcoxon Test ◽  
Control Group ◽  
Maternal Knowledge ◽  
Control Group Design ◽  
Significant Difference

ABSTRACT Toilet training is an effort to train children to be able to control and urinate (BAK) and defecate (BAB). Toilet training is one of the main tasks of children at toddler age. Toilet training is one of the main tasks of children in toddler age which is very important to be done to create independence in children in controlling BAK and BAB and children know the parts of the body and their functions. Data in 2012 shows that ± 60% of parents do not teach toilet training to children from an early age. The aim of the study was to find out the effectiveness of toilet training education on maternal behavior and toilet skills in toddler age training (18-36 months). The study was conducted in July-August 2018. This type of quantitative research used the design of the Quasy pretest and posttest experiment with non-equivalent control group design. Samples were 36 mothers and 36 children with purposive sampling technique. Data analysis used Paired t test, Wilcoxon test, Man-Whitney test an Independent t test. The results showed that toilet training education through lecture methods, modules and maze games was more effective than toilet training education through lecture and leaflet methods on children's knowledge and abilities. Conversely, for the role of mothers in supervision there is no significant difference in effectiveness. Health education is recommended in health promotion programs to increase maternal knowledge, the role of mothers and the ability of toilet training children independently. Keywords: Toilet training, Lecture method, Module, Maze game, Leaflet, Knowledge, Role of mother, Children's ability.

Magistri Legis. Eine Studie zur dogmatischen Funktion im industriellen System

2011 ◽  
Vol 2 (2) ◽  
pp. 69-112
Author(s):  
Pierre Legendre
Keyword(s):  
Social Function ◽  
Modern Human ◽  
Human Behaviour ◽  
Cultural Reproduction ◽  
Industrial System ◽  
The West ◽  
History Of ◽  
History Of Law ◽  
New Look

"Der Beitrag reevaluiert die «dogmatische Funktion», eine soziale Funktion, die mit biologischer und kultureller Reproduktion und folglich der Reproduktion des industriellen Systems zusammenhängt. Indem sie sich auf der Grenze zwischen Anthropologie und Rechtsgeschichte des Westens situiert, nimmt die Studie die psychoanalytische Frage nach der Rolle des Rechts im Verhalten des modernen Menschen erneut in den Blick. </br></br>This article reappraises the dogmatic function, a social function related to biological and cultural reproduction and consequently to the reproduction of the industrial system itself. On the borderline of anthropology and of the history of law – applied to the West – this study takes a new look at the question raised by psychoanalysis concerning the role of law in modern human behaviour. "

Clash of signs: Putting bilingualism back into language evolution

2020 ◽  
Author(s):  
Steven Samuel
Keyword(s):  
Language Evolution ◽  
Modern Human ◽  
Alarm Calls ◽  
Bilingual Children ◽  
Human Language ◽  
Typically Developing ◽  
Typically Developing Children ◽  
Modern Humans ◽  
The Real ◽  
Multiple Languages

Research and thinking into the cognitive aspects of language evolution has usually attempted to account for how the capacity for learning even one modern human language developed. Bilingualism has perhaps been thought of as something to think about only once the ‘real’ puzzle of monolingualism is solved, but this would assume in turn (and without evidence) that bilingualism evolved after monolingualism. All typically-developing children (and adults) are capable of learning multiple languages, and the majority of modern humans are at least bilingual. In this paper I ask whether by skipping bilingualism out of language evolution we have missed a trick. I propose that exposure to synonymous signs, such as food and alarm calls, are a necessary precondition for the abstracting away of sound from referent. In support of this possibility is evidence that modern day bilingual children are better at breaking this ‘word magic’ spell. More generally, language evolution should be viewed through the lens of bilingualism, as this is the end state we are attempting to explain.

SUBLINGUAL VITAMIN D3 DRUG THERAPY IN VITAMIN D DEFICIENCY PATIENTS AT PRAVARA RURAL HOSPITAL

2019 ◽  
pp. 18-20
Author(s):  
Sanjeeva Kumar Goud T ◽  
Rahul Kunkulol
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Vitamin D3 ◽  
Serum Vitamin ◽  
Cross Sectional ◽  
Serum Vitamin D ◽  
Significant Difference ◽  
Before And After

The present study was aimed to study the effect of Sublingual Vitamin D3 on Serum Vitamin D level in Vitamin D deficiency patients. This was a cross-sectional and interventional study. All the Vitamin D deficiency patients of age 18-60years and either gender, willing to participate in the study were included. Patients who had greater than 20 ng/ml were excluded from the study. The total number of participants in our study was 200, out of these 111 males and 89 females, the mean age in our study was 51.07 ± 7.39Yrs. All volunteers were given sublingual vitamin D3 (60,000IU) in six doses every fifteen days of follow up for 3 months. The subject’s serum 25(OH)D levels were estimated before and after the treatment of sublingual vitamin D3. There was a statistically significant difference in serum vitamin D3 level before 16.61±6.71 ng/ml and after 35.80±7.80 ng/ml after treatment with Sublingual Vitamin D3. Six doses of 60,000IU of Vitamin D3 sublingual route having improved the role of serum 25(OH)D levels in the treatment of Vitamin D3 deficiency patients.Keywords: Vitamin D3; Sublingual route

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