Early growth cessation and reproduction are predicted to maximize fitness under conditions of high adult mortality, factors that could explain the pygmy phenotype of many rainforest hunter-gatherers. This life-history hypothesis is... more
Early growth cessation and reproduction are predicted to maximize fitness under conditions of high adult mortality, factors that could explain the pygmy phenotype of many rainforest hunter-gatherers. This life-history hypothesis is elegant but contentious in part because it lacks a clear biological mechanism. One mechanism stems from the field of human immunological ecology and the concept of inflammation “memory” across the life cycle and into subsequent generations. Maternal exposures to disease can influence immunological cues present in breast milk; because maternal provisioning via lactation occurs during critical periods of development, it is plausible that these cues can also mediate early growth cessation and small body size. Such epigenetic hypotheses are difficult to test, but the concept of developmental programming is attractive because it could explain how the stature of a population can change over time, in terms of both secular increases and rapid intergenerational decreases. Here we explore this concept by focusing on the Aeta, a population of former hunter-gatherers, and the Ilocano, a population of rice farmers. We predicted that Aeta mothers would produce breast milk with higher concentrations of four bioactive factors due to high infectious burdens. Further, we predicted that the concentrations of these factors would be highest in the cohort of women born in the early 1990s, when exposure to infectious disease was acute following the eruption of Mount Pinatubo in June 1991. We analyzed levels of adiponectin, C-reactive protein, and epidermal growth factor in the milk of 24 Aeta and 31 Ilocano women and found no detectable differences, whereas levels of transforming growth factor-2 were elevated among the Aeta, particularly as a function of maternal age. We found no difference between cohorts divided by the volcanic eruption (n = 43 born before, n = 12 born after). We discuss the implications of our findings for the terminal investment hypothesis and we suggest that the historical ecology of the Aeta is a promising model system for testing epigenetic hypotheses focused on the evolution of small body size.
A review of the role of the TGF-β-activin-nodal branch in pulmonary arterial hypertension and how this knowledge has not only provided insight into understanding its pathogenesis, but has also paved the way for possible novel therapeutic... more
A review of the role of the TGF-β-activin-nodal branch in pulmonary arterial hypertension and how this knowledge has not only provided insight into understanding its pathogenesis, but has also paved the way for possible novel therapeutic approaches https://bit.ly/2Pujk8O
The transforming growth factor-β (TGF-β) superfamily includes several groups of multifunctional proteins that form two major branches, namely the TGF-β–activin–nodal branch and the bone morphogenetic protein (BMP)–growth differentiation... more
The transforming growth factor-β (TGF-β) superfamily includes several groups of multifunctional proteins that form two major branches, namely the TGF-β–activin–nodal branch and the bone morphogenetic protein (BMP)–growth differentiation factor (GDF) branch. The response to the activation of these two branches, acting through canonical (small mothers against decapentaplegic (Smad) 2/3 and Smad 1/5/8, respectively) and noncanonical signalling pathways, are diverse and vary for different environmental conditions and cell types. An extensive body of data gathered in recent years has demonstrated a central role for the cross-talk between these two branches in a number of cellular processes, which include the regulation of cell proliferation and differentiation, as well as the transduction of signalling cascades for the development and maintenance of different tissues and organs. Importantly, alterations in these pathways, which include heterozygous germline mutations and/or alterations i...
Context: Orthodontic force causes the compression of the periodontal ligament in inhibiting vascularization on the pressure side of orthodontic tooth movement (OTM), while on the opposite side, the periodontal ligament is stretched.... more
Context: Orthodontic force causes the compression of the periodontal ligament in inhibiting vascularization on the pressure side of orthodontic tooth movement (OTM), while on the opposite side, the periodontal ligament is stretched. Hyperbaric oxygen therapy (HBOT) can increase the dissolved oxygen in the blood, which can affect the tissue regeneration of the periodontal ligament. Aims: To evaluate the effect of HBO 2.4 absolute atmospheres (ATA) for 3 × 30 minutes with 5 minutes interval for 7 days as an adjuvant therapy to accelerate periodontal ligament remodeling during OTM in Cavia cobaya. Methods: The study was an experimental laboratory research with a completely randomized design. Twenty-four males C. cobaya were divided into three groups, (X1) as the control group, (X2) as the group with orthodontic force, and (X3) as the group with orthodontic force followed by HBO 2.4 ATA. Matrix Metalloproteinase (MMP)-8 and Transforming Growth Factor (TGF)-β expressions were measured by using immunohistochemistry. OTM was then examined by applying linear distance and analyzed by employing ratio test (p<0.05). Results: Ratio analysis shows HBO 2.4 ATA for 3 × 30 minutes once a day with 5 minutes intervals for 7 days has increased MMP-8 expressions in the pressure area and TGF-β in the tension area (p<0.05). Conclusions: HBO 2.4 ATA for 3 × 30 minutes once a day for 7 with 5 minutes intervals is able to effectively accelerate the periodontal ligament remodeling process expressed by the increased expression MMP-8, especially within the pressure area and TGF-β in the tension area.
Aim: Estrogen receptor-α (ER-α) activation drives the progression of luminal breast cancers. Signaling by transforming growth factor-β (TGF-β) typically opposes the actions of ER-α; it also induces epithelial-mesenchymal transition (EMT)... more
Aim: Estrogen receptor-α (ER-α) activation drives the progression of luminal breast cancers. Signaling by transforming growth factor-β (TGF-β) typically opposes the actions of ER-α; it also induces epithelial-mesenchymal transition (EMT) programs that promote breast cancer dissemination, stemness and chemoresistance. The impact of EMT programs on nongenomic ER-α signaling remains unknown and was studied herein.
Methods: MCF-7 and BT474 cells were stimulated with TGF-β to induce EMT programs, at which point ER-α expression, localization, and nongenomic interactions with receptor tyrosine kinases and MAP kinases (MAPKs) were determined. Cell sensitivity to anti-estrogens both before and after traversing the EMT program was also investigated.
Results: TGF-β-stimulated MCF-7 and BT474 cells to acquire EMT phenotypes, which enhanced cytoplasmic accumulation of ER-α without altering its expression. Post-EMT cells exhibited: (1) elevated expression of EGFR and IGF1R, which together with Src formed cytoplasmic complexes with ER-α; (2) enhanced coupling of EGF, IGF-1 and estrogen to the activation of MAPKs; and (3) reduced sensitivity to tamoxifen, an event reversed by administration of small molecule inhibitors against the receptors for TGF-β, EGF, and IGF-1, as well as those against MAPKs.
Conclusion: EMT stimulated by TGF-β promotes anti-estrogen resistance by activating EGFR-, IGF1R-, and MAPK-dependent nongenomic ER-α signaling.
