Evolutionary fitness as a function of pubertal age in 22 subsistence-based traditional societies

<p>Abstract</p> <p>Context</p> <p>The age of puberty has fallen over the past 130 years in industrialized, western countries, and this fall is widely referred to as the secular trend for earlier puberty. The current study was undertaken to test two evolutionary theories: (a) the reproductive system maximizes the number of offspring in response to positive environmental cues in terms of energy balance, and (b) early puberty is a trade-off response for high mortality rate and reduced resource availability.</p> <p>Methods</p> <p>Using a sample of 22 natural-fertility societies of mostly tropical foragers, horticulturalists, and pastoralists from Africa, South America, Australia, and Southeastern Asia, this study compares indices of adolescence growth and menarche with those of fertility fitness in these non-industrial, traditional societies.</p> <p>Results</p> <p>The average age at menarche correlated with the first reproduction, but did not correlate with the total fertility rate TFR or reproductive fitness. The age at menarche correlated negatively with their average adult body mass, and the average adult body weight positively correlated with reproductive fitness. Survivorship did not correlate with the age at menarche or age indices of the adolescent growth spurt. The population density correlated positively with the age at first reproduction, but not with menarche age, TFR, or reproductive fitness.</p> <p>Conclusions</p> <p>Based on our analyses, we reject the working hypotheses that reproductive fitness is enhanced in societies with early puberty or that early menarche is an adaptive response to greater mortality risk. Whereas body mass is a measure of resources is tightly associated with fitness, the age of menarche is not.</p

A simple rule governs the evolution and development of hominin tooth size

The variation in molar tooth size in humans and our closest relatives (hominins) has strongly influenced our view of human evolution. The reduction in overall size and disproportionate decrease in third molar size have been noted for over a century, and have been attributed to reduced selection for large dentitions owing to changes in diet or the acquisition of cooking1, 2. The systematic pattern of size variation along the tooth row has been described as a ‘morphogenetic gradient’ in mammal, and more specifically hominin, teeth since Butler3 and Dahlberg4. However, the underlying controls of tooth size have not been well understood, with hypotheses ranging from morphogenetic fields3 to the clone theory5. In this study we address the following question: are there rules that govern how hominin tooth size evolves? Here we propose that the inhibitory cascade, an activator–inhibitor mechanism that affects relative tooth size in mammals6, produces the default pattern of tooth sizes for all lower primary postcanine teeth (deciduous premolars and permanent molars) in hominins. This configuration is also equivalent to a morphogenetic gradient, finally pointing to a mechanism that can generate this gradient. The pattern of tooth size remains constant with absolute size in australopiths (including Ardipithecus, Australopithecus and Paranthropus). However, in species of Homo, including modern humans, there is a tight link between tooth proportions and absolute size such that a single developmental parameter can explain both the relative and absolute sizes of primary postcanine teeth. On the basis of the relationship of inhibitory cascade patterning with size, we can use the size at one tooth position to predict the sizes of the remaining four primary postcanine teeth in the row for hominins. Our study provides a development-based expectation to examine the evolution of the unique proportions of human teeth

Morphometrics as an Insight Into Processes Beyond Tooth Shape Variation in a Bank Vole Population

Phenotype variation is a key feature in evolution, being produced by development and the target of the screening by selection. We focus here on a variable morphological feature: the third upper molar (UM3) of the bank vole, aiming at identifying the sources of this variation. Size and shape of the UM3 occlusal surface was quantified in successive samples of a bank vole population. The first source of variation was the season of trapping, due to differences in the age structure of the population in turn affecting the wear of the teeth. The second direction of variation corresponded to the occurrence, or not, of an additional triangle on the tooth. This intra-specific variation was attributed to the space available at the posterior end of the UM3, allowing or not the addition of a further triangle.This size variation triggering the shape polymorphism is not controlled by the developmental cascade along the molar row. This suggests that other sources of size variation, possibly epigenetic, might be involved. They would trigger an important shape variation as side-effect by affecting the termination of the sequential addition of triangles on the tooth

Investigating the efficacy of transcription factor-specific DNAzymes in animal models of inflammatory skin diseases

Inflammatory skin diseases cover a wide range of skin conditions that cause dry, itchy, scaly skin and affects millions around the world. Current therapies are mostly symptomatic and often associated with a wide range of side effects. Therefore, there is a growing need for a more specific therapy targeting key molecules in the pathogenesis of such diseases. Investigations revealed a central role for different T helper subsets in the immunopathology of these skin diseases. Atopic dermatitis (Th2), contact dermatitis (Th1) and Psoriasis (Th1, Th17), are associated with one or more of these Th-phenotypes. The differentiation and activation of T helper subtypes is regulated by different transcription factors. This study focused on two specific transcription factors GATA3 and Tbet, which regulate the differentiation and activation of Th2 and Th1, respectively. The levels of these transcription factors were found to be elevated in diseases with the respective Th phenotype, which made them interesting targets for DNAzyme-based therapy. In order to test the efficacy of such transcription factor-specific DNAzymes, two different animal models of inflammatory allergic skin diseases were established. In the first model skin injury and the hapten oxazolone were used to elicit a Th2-dominant contact hypersensitivity with features similar to those of atopic dermatitis. In the second model, Ovalbumin was used to induce a Th1-dominated inflammation in OVA-specific T cell receptor- transgenic mice after systemic sensitization with OVA/CFA. Effects of topical preventive treatment with GATA3-specific DNAzyme (hgd40) were investigated in the oxazolone model. The DNAzymes were formulated in w/o/w emulsion for protection against degradation and an enhanced skin penetration. Compared to placebo and control non-specific DNAzyme ODNg3, prophylactic treatment with hgd40 significantly reduced skin swelling. It also resulted in lower numbers of CD4+ cells infiltrating the dermis. This was associated with a downregulation of GATA3 mRNA expression in the skin early in the sensitization phase. Similar reduction in skin swelling was also observed after a semi-therapeutic treatment, in which hgd40 was first applied 24 h prior to challenge but not during sensitization. Using the OVA/CFA model, effects of the Tbet-specific DNAzyme td32 treatment were evaluated. Data indicated a significant reduction in skin swelling following prophylactic treatment with emulsions containing td32. No such effect was observed in the control DNAzyme ODNg3 or placebo groups. In addition, no influence on the progression of skin swelling in this Th1-skewed skin inflammation after treatment with hgd40 was detected, which further supports the hypothesis of specific targeting of Tbet. In summary, this study shows that treatment with DNAzymes, targeting Th1- and Th2- specific transcription factors Tbet and GATA3 improved inflammatory symptoms in vivo. These results pose the DNAzyme as promising tools for future topical treatment of inflammatory skin diseases

Rolle von T-Zellen bei COPD: Einfluss von Zigarettenrauch-Komponenten auf Differenzierungsprozesse von Th-Subpopulationen

Die chronisch obstruktive Lungenerkrankung (COPD) ist eine weit verbreitete chronisch-entzündliche Erkrankung der Lunge, die mit weltweit steigenden Mortalitätsraten assoziiert ist. Die häufigste Ursache der COPD ist chronische Rauchexposition. Die pathogenen Mechanismen, die zur Ausprägung der Erkrankung führen, sind bisher noch weitgehend unklar. Allerdings wird aktuell diskutiert, dass autoimmune Prozesse, wahrscheinlich gerichtet gegen degradierte Komponenten der extrazellulären Matrix und dabei Th1/Th17 Zellen an der Induktion und/oder Perpetuierung der Erkrankung beteiligt sind. Vor diesem Hintergrund verfolgen wir die Hypothese, dass Zigarettenrauch einen direkten modifizierenden Einfluss auf die Differenzierung von T-Helferzellen hat. Um diese Hypothese zu testen, wurde der Einfluss von Zigarettenrauch- konditioniertem Medium (CSE) auf die Entwicklung von naїven und differenzierten T-Zellen in vitro untersucht. Diese Ergebnisse wurden anhand eines murinen chronischen Rauchexpositionsmodells in vivo evaluiert. Die Aktivität verschiedener Th Subtypen wurde mithilfe von mRNA Expressionsanalysen, intrazellulären FACS Messungen, Sekretionsassay und cytokine cytometric bead assay bestimmt. In vitro verzögert CSE die Proliferation von Th1 Zellen, unterstützt aber gleichzeitig deren Differenzierung nachgewiesen durch eine signifikant höhere IFN + Produktion. Gleichzeitig inhibiert CSE die Differenzierung von Tregs deutlich. Die Gabe von CSE auf bereits differenzierte Th Subtypen zeigte, dass im Gegensatz zu Th1 Zellen bereits differenzierte Th17 Zellen stabilisiert bzw. unterstützt werden. Außerdem konnte gezeigt werden, dass CSE während der Th2 Polarisation zu einem Wechsel zu einem IL-9 produzierenden Phänotyp führt und die IL-9 Produktion in Th9 Zellen signifikant induziert bzw. verstärkt. Diese in vitro Ergebnisse konnten in vivo verifiziert werden. Die chronische Exposition von Zigarettenrauch führte systemisch zu einer signifikant reduzierten relativen Zellzahl von Tregs und lokal (Lunge) zu einer signifikant gesteigerten relativen Zellzahl von IL-17+ und IL-9+ CD4+-Zellen. Mit diesen Ergebnissen kann erstmalig gezeigt werden, dass Zigarettenrauch-Komponenten einen direkten Einfluss auf die Differenzierung und Aktivierung von verschiedenen Th Subtypen hat. Dabei wird ein potentiell autoimmun-assoziierter inflammatorischer Phänotyp mit verstärkter Th1 Aktivität, stabilen Th17 Zellen, weniger Tregs und einer gesteigerten IL-9 Produktion generiert. Somit führt Zigarettenrauch-Exposition zu Änderungen des lokalen Zytokin-Milieus, welches eine chronische Inflammation und autoimmune Prozesse unterstützen und so einen wesentlichen Einfluss auf die Pathogenese in der COPD haben kann