Anthropometric study of the facial index in the population of Central Serbia

The aim of this study was to determine the craniofacial parameters in the population of the central part of Serbia. The research was conducted on 700 persons (360 males and 340 females), aged 18-65 years, selected randomly. The measured parameters were morphological facial height and breadth. The standard spreading caliper with scale was used for the measurement of facial parameters. There were significant differences in the facial parameters of male compared to female subjects in all observed parameters. The mean value of the morphological facial height in the study population was 116.8 mm ± 7.28, maximum facial breadth 124.12 mm ± 8.44, while the mean value of the total facial index was 93.68 ± 6.86. The total facial index was calculated according to the formula and the obtained results were analyzed statistically using the t-test. The dominant phenotype in the studied population was leptoprosopic. The data obtained in our study may be useful in anthropological research, forensics, genetic research, as well as in medical clinical practice

Differential requirements for the canonical NF-κB transcription factors c-REL and RELA during the generation and activation of mature B cells

Signaling through the canonical nuclear factor‐κB (NF‐κB) pathway is critical for the generation and maintenance of mature B cells and for antigen‐dependent B‐cell activation. c‐REL (rel) and RELA (rela) are the downstream transcriptional activators of the canonical NF‐κB pathway. Studies of B cells derived from constitutional rel knockout mice and chimeric mice repopulated with rela–/– fetal liver cells provided evidence that the subunits can have distinct roles during B‐cell development. However, the B cell‐intrinsic functions of c‐REL and RELA during B‐cell generation and antigen‐dependent B‐cell activation have not been determined in vivo. To clarify this issue, we crossed mice with conditional rel and rela alleles individually or in combination to mice that express Cre‐recombinase in B cells. We here report that, whereas single deletion of rel or rela did not impair mature B‐cell generation and maintenance, their simultaneous deletion led to a dramatic reduction of follicular and marginal zone B cells. Upon T cell‐dependent immunization, B cell‐specific deletion of the c‐REL subunit alone abrogated the formation of germinal centers (GCs), whereas rela deletion did not affect GC formation. T‐independent responses were strongly impaired in mice with B cell‐specific deletion of rel, and only modestly in mice with RELA‐deficient B cells. Our findings identify differential requirements for the canonical NF‐κB subunits c‐REL and RELA at distinct stages of mature B‐cell development. The subunits are jointly required for the generation of mature B cells. During antigen‐dependent B‐cell activation, c‐REL is the critical subunit required for the initiation of the GC reaction and for optimal T‐independent antibody responses, with RELA being largely dispensable at this stage

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe

Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants

Background Hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories. Methods We used data from 1990 to 2019 on people aged 30-79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment. We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension. We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled to below 140/90 mm Hg (control). The model allowed for trends over time to be non-linear and to vary by age. Findings The number of people aged 30-79 years with hypertension doubled from 1990 to 2019, from 331 (95% credible interval 306-359) million women and 317 (292-344) million men in 1990 to 626 (584-668) million women and 652 (604-698) million men in 2019, despite stable global age-standardised prevalence. In 2019, age-standardised hypertension prevalence was lowest in Canada and Peru for both men and women; in Taiwan, South Korea, Japan, and some countries in western Europe including Switzerland, Spain, and the UK for women; and in several low-income and middle-income countries such as Eritrea, Bangladesh, Ethiopia, and Solomon Islands for men. Hypertension prevalence surpassed 50% for women in two countries and men in nine countries, in central and eastern Europe, central Asia, Oceania, and Latin America. Globally, 59% (55-62) of women and 49% (46-52) of men with hypertension reported a previous diagnosis of hypertension in 2019, and 47% (43-51) of women and 38% (35-41) of men were treated. Control rates among people with hypertension in 2019 were 23% (20-27) for women and 18% (16-21) for men. In 2019, treatment and control rates were highest in South Korea, Canada, and Iceland (treatment >70%; control >50%), followed by the USA, Costa Rica, Germany, Portugal, and Taiwan. Treatment rates were less than 25% for women and less than 20% for men in Nepal, Indonesia, and some countries in sub-Saharan Africa and Oceania. Control rates were below 10% for women and men in these countries and for men in some countries in north Africa, central and south Asia, and eastern Europe. Treatment and control rates have improved in most countries since 1990, but we found little change in most countries in sub-Saharan Africa and Oceania. Improvements were largest in high-income countries, central Europe, and some upper-middle-income and recently high-income countries including Costa Rica, Taiwan, Kazakhstan, South Africa, Brazil, Chile, Turkey, and Iran. Interpretation Improvements in the detection, treatment, and control of hypertension have varied substantially across countries, with some middle-income countries now outperforming most high-income nations. The dual approach of reducing hypertension prevalence through primary prevention and enhancing its treatment and control is achievable not only in high-income countries but also in low-income and middle-income settings. Copyright (C) 2021 World Health Organization; licensee Elsevier

Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants

Background Hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories. Methods We used data from 1990 to 2019 on people aged 30–79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment. We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension. We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled to below 140/90 mm Hg (control). The model allowed for trends over time to be non-linear and to vary by age. Findings The number of people aged 30–79 years with hypertension doubled from 1990 to 2019, from 331 (95% credible interval 306–359) million women and 317 (292–344) million men in 1990 to 626 (584–668) million women and 652 (604–698) million men in 2019, despite stable global age-standardised prevalence. In 2019, age-standardised hypertension prevalence was lowest in Canada and Peru for both men and women; in Taiwan, South Korea, Japan, and some countries in western Europe including Switzerland, Spain, and the UK for women; and in several low-income and middle-income countries such as Eritrea, Bangladesh, Ethiopia, and Solomon Islands for men. Hypertension prevalence surpassed 50% for women in two countries and men in nine countries, in central and eastern Europe, central Asia, Oceania, and Latin America. Globally, 59% (55–62) of women and 49% (46–52) of men with hypertension reported a previous diagnosis of hypertension in 2019, and 47% (43–51) of women and 38% (35–41) of men were treated. Control rates among people with hypertension in 2019 were 23% (20–27) for women and 18% (16–21) for men. In 2019, treatment and control rates were highest in South Korea, Canada, and Iceland (treatment >70%; control >50%), followed by the USA, Costa Rica, Germany, Portugal, and Taiwan. Treatment rates were less than 25% for women and less than 20% for men in Nepal, Indonesia, and some countries in sub-Saharan Africa and Oceania. Control rates were below 10% for women and men in these countries and for men in some countries in north Africa, central and south Asia, and eastern Europe. Treatment and control rates have improved in most countries since 1990, but we found little change in most countries in sub-Saharan Africa and Oceania. Improvements were largest in high-income countries, central Europe, and some upper-middle-income and recently high-income countries including Costa Rica, Taiwan, Kazakhstan, South Africa, Brazil, Chile, Turkey, and Iran. Interpretation Improvements in the detection, treatment, and control of hypertension have varied substantially across countries, with some middle-income countries now outperforming most high-income nations. The dual approach of reducing hypertension prevalence through primary prevention and enhancing its treatment and control is achievable not only in high-income countries but also in low-income and middle-income settings

Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants.

BACKGROUND: Hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories. METHODS: We used data from 1990 to 2019 on people aged 30-79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment. We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension. We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled to below 140/90 mm Hg (control). The model allowed for trends over time to be non-linear and to vary by age. FINDINGS: The number of people aged 30-79 years with hypertension doubled from 1990 to 2019, from 331 (95% credible interval 306-359) million women and 317 (292-344) million men in 1990 to 626 (584-668) million women and 652 (604-698) million men in 2019, despite stable global age-standardised prevalence. In 2019, age-standardised hypertension prevalence was lowest in Canada and Peru for both men and women; in Taiwan, South Korea, Japan, and some countries in western Europe including Switzerland, Spain, and the UK for women; and in several low-income and middle-income countries such as Eritrea, Bangladesh, Ethiopia, and Solomon Islands for men. Hypertension prevalence surpassed 50% for women in two countries and men in nine countries, in central and eastern Europe, central Asia, Oceania, and Latin America. Globally, 59% (55-62) of women and 49% (46-52) of men with hypertension reported a previous diagnosis of hypertension in 2019, and 47% (43-51) of women and 38% (35-41) of men were treated. Control rates among people with hypertension in 2019 were 23% (20-27) for women and 18% (16-21) for men. In 2019, treatment and control rates were highest in South Korea, Canada, and Iceland (treatment >70%; control >50%), followed by the USA, Costa Rica, Germany, Portugal, and Taiwan. Treatment rates were less than 25% for women and less than 20% for men in Nepal, Indonesia, and some countries in sub-Saharan Africa and Oceania. Control rates were below 10% for women and men in these countries and for men in some countries in north Africa, central and south Asia, and eastern Europe. Treatment and control rates have improved in most countries since 1990, but we found little change in most countries in sub-Saharan Africa and Oceania. Improvements were largest in high-income countries, central Europe, and some upper-middle-income and recently high-income countries including Costa Rica, Taiwan, Kazakhstan, South Africa, Brazil, Chile, Turkey, and Iran. INTERPRETATION: Improvements in the detection, treatment, and control of hypertension have varied substantially across countries, with some middle-income countries now outperforming most high-income nations. The dual approach of reducing hypertension prevalence through primary prevention and enhancing its treatment and control is achievable not only in high-income countries but also in low-income and middle-income settings. FUNDING: WHO

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions

Die Rolle der Transkriptionsfaktoren Icsbp und Klf4 in der Enwicklung Myeloider Zellen

Title 1. Introduction 1 2. Problem statement 18 3. Materials 19 4. Methods 26 5\. Results 45 6. Discussion 95 7. Conclusions 105 8. Summary 106 9. Zusammenfassung 108 References 111 Appendix 127Icsbp deletion leads to changed differentiation program of myeloid progenitors reflected in high production of granulocytes and low production of macrophages. In order to study the underlying mechanism of this switch, the gene expression profiles of isolated granulocyte-macrophage progenitors (GMP) from Icsbp+/+ and Icsbp-/- mice were compared, revealing deregulation of other hematopoietic transcription factors. The goal of this work was to investigate the contribution of one of these additional deregulations to the observed Icsbp-/- mouse phenotype, namely the down-regulation of the transcription factor Klf4. The experiments described in this work identify Klf4 as a factor which has a strong influence on myeloid progenitors, directing them to differentiate along the macrophage lineage, as shown by significantly higher percentage of macrophage colonies developing from Klf4-ERT2 over-expressing myeloid progenitors. Klf4-ERT2 led to the macrophage maturation even when the progenitors were cultured with granulocyte-colony stimulating factor (G- CSF) or when expressed in the Icsbp-/- cells (which have propensity to form granulocytes), suggesting the ability of Klf4 to override granulocyte- promoting effects of both extracellular and intracellular signals and reprogram the cell fate to the macrophage lineage. Up-regulation of several putative macrophage genes and down-regulation of genes involved in granulocyte proliferation suggested that Klf4 exerts it macrophage promoting effect by coordinating molecular changes which precede the commitment to this lineage. Another feature of the Klf4-ERT2 over-expression is its strong cytostatic effect on developing myeloid cells, suggesting that Klf4 acts as a proliferation/differentiation switch in the myeloid development. p21Waf1 is Klf4 transcriptional targets whose contribution to the Klf4 effects on myeloid cells was analyzed by over-expressing p21Waf1 in Klf4+/+ and Klf4-/- myeloid progenitors. In addition to the full-length p21Waf1 over-expression, the compartmentalized p21Waf1 expression was simulated by the ability of the p21-ERT2 fusion construct to translocate in the nucleus in the presence of the ERT2-ligand or to stay sequestered in the cytosol in the ligand absence. Enhanced macrophage formation was observed in all cases of forced p21Waf1 expression, suggesting that p21Waf1 itself enhances macrophage maturation. Since the reduction in the colony formation was observed only when p21Waf1 was allowed to enter the nucleus, we conclude that the roles of p21Waf1 in differentiation and cell cycle control can be decoupled and depend on the subcellular localization of p21Waf1. Another aspect of myelopoiesis, development of eosinophilic granulocytes, was analyzed. The gene profiling of Icsbp+/+ and Icsbp-/- GMPs identified strong down-regulation of several eosinophil-specific genes in the absence of Icsbp, suggesting perturbed eosinophilopoiesis. We confirmed that Icsbp-/- eosinophil progenitors are reduced in number and have aberrant differentiation profile. This defective eosinophil proliferation is based on reduced expression of the main eosinophil growth factor receptor, Il-5Rα and reduced expression of an important eosinophil intrinsic factor, Gata1. Summarized, this work identifies Klf4 as novel macrophage maturation promoting factor, whose effects in myelopoiesis are partially mediated by its downstream target p21Waf. Additionally, this work revealed previously undetected myeloipoietic defect in Icsbp-/- mice, namely perturbed development of eosinophils, identifying thereby Icsbp as an important factor in eosinophilopoiesis.Der Icsbp Knockout veraendert das Differenzierungsprogramm myeloider Progenitoren, was sich in einer erhoehten Produktion von Granulozyten und einer erniedrigten Produktion von Makrophagen manifestiert. Um den zugrunde liegenden Mechanismen fuer diese Veraenderung auf die Spur zu kommen, wurden Granulozyten-Makrophagen-Vorlaeuferzellen (GMP) aus Icsbp+/+ und Icsbp-/- Maeusen isoliert und ihre Expressionsmuster verglichen. Diese Analyse offenbarte eine Deregulierung mehrerer haematopoietischer Transkriptionsfaktoren. Ziel dieser Arbeit war es, den Beitrag einer dieser zusaetzlichen Deregulierungen zum Icsbp-/- Phaenotyp zu untersuchen, der Herabregulierung des Klf4 Transkriptionsfaktors. Die in dieser Arbeit vorgestellten Ergebnisse zeigen, dass Klf4 die Entwicklung myeloider Progenitoren erheblich beeinflusst, indem er die Differenzierung entlang der Makrophagenlinie steuert, was sich anhand der signifikant erhoehten Prozentsaetze von Makrophagenkolonien erkennen laesst, die sich aus Klf4-ERT2 ueberexprimierenden myeloiden Progenitoren entwickeln. Klf4-ERT2 ueberexpression fuehrt sogar zu vermehrter Makrophagenreifung, wenn die Kolonien in G-SCF kultiviert werden oder wenn Klf4-ERT2 in Icsbp-/- Zellen (die eine verstaerkte Neigung haben, Granulozyten zu bilden) exprimiert wird. Durch die Klf4 Ueberexpression koennen also offenbar sowohl extrazellulaere als auch intrazellulaere Granulozyten-foerdernde Faktoren uebergangen werden und die Entwicklung der Zellen in Richtung Makrophagen gesteuert werden. Die Heraufregulierung mehrerer mutmasslich Makrophagen-spezifischer Gene und die Herabregulierung von Genen, die in die Granulozytenentwicklung involviert sind deuten darauf hin, dass Klf4 seinen Makrophagen-foerdernden Effekt durch die Koordinierung molekularer Veraenderungen ausuebt, die der Festlegung auf diese Linie vorausgehen. Ein weiteres Merkmal der Klf4 Ueberexpression besteht in einem starken zytostatischen Effekt auf die sich entwickelnden myeloiden Zellen, was deutet auf eine Funktion von Klf4 als Proliferations/Differenzierungsschalter in der myeloiden Entwicklung hin. p21Waf1 ist eines der durch Klf4 regulierten Gene, dessen Beitrag zu den bei Klf4 verursachten Veraenderungen bei der Entwicklung myeloider Progenitoren, durch p21Waf1 Uberexprimierung in Klf4+/+ und Klf4-/- myeloiden Progenitoren analysiert wurde. Zudem wurde die kompartimentalisierte Ueberexpression von p21Waf1 getestet, indem ein p21- ERT2 Konstrukt durch Zugabe des ERT2-Liganden dazu gebracht wurde, in den Zellkern zu wandern, waehrend es ohne Ligand im Cytosol verblieb. Sowohl bei cytosolischer, als auch bei nukleaerer Ueberexpression von p21Waf1 kam es zu einer verstaerkten Bildung von Makrophagen. Dies deutet darauf hin, dass p21Waf1 fuer den Phaenotyp der Klf4 Ueberexprimierenden Zellen verantwortlich ist. Da der zytostatische Effekt nur dann beobachtet wurde, wenn p21Waf1 in den Zellkern translozieren konnte, koennen wir feststellen, dass die Rollen von p21Waf1 bei Zelldifferenzierung und Zellwachstum unabhaengig voneinander sind und haengen von der subzellulären Lokalisierung des Faktors ab. Neben der Analyse der Faktoren, die die Entwicklung von Makrophagen und neutrophiler Granulozyten steuern, wurde noch ein anderer Aspekt der Myelopoiese untersucht: die Entwicklung eosinophiler Granulozyten. Der Vergleich der Expressionsmuster der Icsbp+/+ und Icsbp-/- GMP ergab eine starke Herabregulierung mehrerer eosinophil- spezifischer Gene, was eine gestoerte Eosiniphilopoiese in Icsbp-/- Maeusen vermuten liess. Tatsaechlich konnte eine reduzierte Zahl und gestoerte Diferenzierungs Potenzial von eosinophilen Progenitoren in Icsbp-/- Maeusen beobachtet werden. Die defekte Proliferation der Icsbp-/- Eosinophilen laesst sich auf eine verminderte Expression des wichtigsten Eosinophilen- Wachstumsfaktors, Il5-R(Alpha) und eines wichtigen intrinsischen Faktors, Gata1 zurueckfuehren. Durch diese Arbeit konnte Klf4 als ein neuer Makroplagen-Reifungs- Faktor identifiziert werden, dessen Effekte auf die Myelopoiese zumindest teilweise durch sein Zielgen p21Waf1 ausgeuebt werden. Zudem wurde in dieser Arbeit als ein bisher unbekannter myelopoietischer Defekt die gestoerte Entwicklung in Icsbp-/- Maeusen entdeckt, wodurch Icsbp als ein wichtiger Faktor in der Eosinophilopoiese identifiziert wurde