Reconstruction of proliferative activity of hair follicle cells based on the geometric parameters of the hair shaft
Proliferative activity and differentiation rate of hair follicle cells determine the shape of the hair and parameters of hair growth. The hair growth rate and changes of geometric parameters of the hair shaft during its elongation (in time) are analyzed to reconstruct the proliferation dynamics of follicle matrix cells. The reconstruction demonstrated that the number of cells of hair follicle matrix increases in a typical manner, including the phase of exponential growth and the stationary phase.
A systems biology approach to the human hair cycle
?A Systems Biology Approach to the Human Hair Cycle?. A thesis submitted to The University of Manchester for the degree of Doctor of Philosophy by Yusur Mamoon Al-Nuaimi, 2011.The hair cycle represents a dynamic process during which a complex mini- organ, the hair follicle, rhythmically regresses and regenerates. The control mechanism that governs the hair cycle (?hair cycle clock?) is thought to be an autonomous oscillator system, however, its exact nature is not known. This thesis aims to understand the human hair cycle as a systems biology problem using theoretical and experimental techniques in three distinct study approaches.Using mathematical modelling, a simple two-compartment model of the human hair cycle was developed. The model concentrates on the growth control of matrix keratinocytes, a key cell population responsible for hair growth, and bi-directional communication between these cells and the inductive fibroblasts of the dermal papilla. A bistable switch and feedback inhibition produces key characteristics of human hair cycle dynamics. This study represents the first mathematically formulated theory of the ?hair cycle clock?.A second chronobiological approach was adopted to explore the molecular control of the human hair follicle by a peripheral clock mechanism. The hypothesis was tested that selected circadian clock genes regulate the human hair cycle, namely the clinically crucial follicle transformation from organ growth (anagen) to organ regression (catagen). This revealed that intra- follicular expression of core clock and clock-controlled genes display a circadian rhythm and is hair cycle-dependent. Knock-down of Period1 and Clock promotes anagen maintenance, hair matrix keratinocyte proliferation and stimulates hair follicle pigmentation. This provides the first evidence that peripheral Period1 and Clock gene activity is a component of the human ?hair cycle clock? mechanism.Lastly, an unbiased gene expression profiling approach was adopted to establish important genes and signalling pathways that regulate the human hair cycle. This revealed that similar genes and pathways previously shown to control the murine hair cycle in vivo, such as Sgk3, Msx2 and the BMP pathway, are also differentially regulated during the anagen-catagen transformation of human hair follicles.In summary, by using a three-pronged systems biology approach, the thesis has shed new light on the control of human hair follicle cycling and has generated clinically relevant information: a) The hair cycle model may predict how hair cycle modulatory agents alter human hair growth. b) Period1 and Clock are new therapeutic targets for human hair growth manipulation. c) Gene expression profiling points to additional key players in human hair cycle control with potential for future therapeutic targets.
High‐precision U‐Pb zircon age calibration of the global Carboniferous time scale and Milankovitch band cyclicity in the Donets Basin, eastern Ukraine
High‐precision ID‐TIMS U‐Pb zircon ages for 12 interstratified tuffs and tonsteins are used to radiometrically calibrate the detailed lithostratigraphic, cyclostratigraphic, and biostratigraphic framework of the Carboniferous Donets Basin of eastern Europe. Chemical abrasion of zircons, use of the internationally calibrated EARTHTIME mixed U‐Pb isotope dilution tracer, and improved mass spectrometry guided by detailed error analysis have resulted in an age resolution of <0.05%, or ∼100 ka, for these Carboniferous volcanics. This precision allows the resolution of time in the Milankovitch band and confirms the long‐standing hypothesis that individual high‐frequency Pennsylvanian cyclothems and bundles of cyclothems into fourth‐order sequences are the eustatic response to orbital eccentricity (∼100 and 400 ka) forcing. Tuning of the fourth‐order sequences in the Donets Basin to the long‐period eccentricity cycle results in a continuous age model for the Middle to Late Pennsylvanian (Moscovian‐Kasimovian‐Ghzelian) strata of the basin and their record of biological and climatic changes through the latter portion of the late Paleozoic Ice Age. Detailed fusulinid and conodont zonations allow the export of this age model to sections throughout Euramerica. Additional ages for Mississippian strata provide among the first robust radiometric calibration points within this subperiod and result in variable lowering of the base ages of its constituent stages compared to recent global time scale compilations.