scholarly journals Population level rhythms in human skin: implications for circadian medicine

2018 ◽  
Author(s):  
Gang Wu ◽  
Marc D. Ruben ◽  
Robert E. Schmidt ◽  
Lauren J. Francey ◽  
David F. Smith ◽  
...  
Keyword(s):  
Human Skin ◽  
Clock Genes ◽  
Human Subjects ◽  
Population Level ◽  
The Body ◽  
Single Sample ◽  
Circadian Phase ◽  
Important Barrier ◽  
Population Scale

AbstractSkin is the largest organ in the body and serves important barrier, regulatory, and sensory functions. Like other tissues, skin is subject to temporal fluctuations in physiological responses under both homeostatic and stressed states. To gain insight into these fluctuations, we investigated the role of the circadian clock in the transcriptional regulation of epidermis using a hybrid experimental design, where a limited set of human subjects (n=20) were sampled throughout the 24 h cycle and a larger population (n=219) were sampled once. By looking at pairwise correlations of core clock genes in 298 skin samples, we found a robust circadian oscillator in skin at the population level. Encouraged by this, we used CYCLOPS to reconstruct the temporal order of all samples and identified hundreds of rhythmically-expressed genes at the population level in human skin. We compared these results with published time-series skin data from mouse and show strong concordance in circadian phase across species for both transcripts and pathways. Further, like blood, skin is readily accessible and a potential source of biomarkers. Using ZeitZeiger, we identified a biomarker set for human skin that is capable of reporting circadian phase to within 3 h from a single sample. In summary, we show rhythms in human skin that persist at the population scale and a path to develop robust single-sample circadian biomarkers.One Sentence SummaryHuman epidermis shows strong circadian rhythms at the population scale and provides a better source for developing robust, single-sample circadian phase biomarkers than human blood.

scholarly journals Population-level rhythms in human skin with implications for circadian medicine

2018 ◽  
Vol 115 (48) ◽  
pp. 12313-12318 ◽  
Author(s):  
Gang Wu ◽  
Marc D. Ruben ◽  
Robert E. Schmidt ◽  
Lauren J. Francey ◽  
David F. Smith ◽  
...  
Keyword(s):  
Human Subjects ◽  
Population Level ◽  
The Body ◽  
Human Epidermis ◽  
Single Sample ◽  
Circadian Phase ◽  
Potential Source ◽  
Pairwise Correlations ◽  
Important Barrier

Skin is the largest organ in the body and serves important barrier, regulatory, and sensory functions. The epidermal layer shows rhythmic physiological responses to daily environmental variation (e.g., DNA repair). We investigated the role of the circadian clock in the transcriptional regulation of epidermis using a hybrid experimental design, in which a limited set of human subjects (n = 20) were sampled throughout the 24-h cycle and a larger population (n = 219) were sampled once. We found a robust circadian oscillator in human epidermis at the population level using pairwise correlations of clock and clock-associated genes in 298 epidermis samples. We then used CYCLOPS to reconstruct the temporal order of all samples, and identified hundreds of rhythmically expressed genes at the population level in human epidermis. We compared these results with published time-series skin data from mice and found a strong concordance in circadian phase across species for both transcripts and pathways. Furthermore, like blood, epidermis is readily accessible and a potential source of biomarkers. Using ZeitZeiger, we identified a biomarker set for human epidermis that is capable of reporting circadian phase to within 3 hours from a single sample. In summary, we show rhythms in human epidermis that persist at the population scale and describe a path to develop robust single-sample circadian biomarkers.

Evidence for the involvement of peripheral cold-sensitive TRPM8 channels in human cutaneous hygrosensation

2020 ◽  
Vol 318 (3) ◽  
pp. R579-R589 ◽  
Author(s):  
Oliver Typolt ◽  
Davide Filingeri
Keyword(s):  
Human Skin ◽  
Chemical Activation ◽  
The Body ◽  
Cold Sensitivity ◽  
Trpm8 Channel ◽  
Body Regions ◽  
Skin Cooling ◽  
Cold Sensitive ◽  
Skin Wetness

In contrast to other species, humans are believed to lack hygroreceptors for sensing skin wetness. Yet, the molecular basis of human hygrosensation is currently unknown, and it remains unclear whether we possess a receptor-mediated sensing mechanism for skin wetness. The aim of this study was to assess the role of the cutaneous cold-sensitive transient receptor potential melastatin-8 (TRPM8) channel as a molecular mediator of human hygrosensation. To this end, we exploited both the thermal and chemical activation of TRPM8-expressing cutaneous Aδ cold thermoreceptors, and we assessed wetness sensing in healthy young men in response to 1) dry skin cooling in the TRPM8 range of thermosensitivity and 2) application of the TRPM8 agonist menthol. Our results indicate that 1) independently of contact with moisture, a cold-dry stimulus in the TRPM8 range of activation induced wetness perceptions across 12 different body regions and those wetness perceptions varied across the body following regional differences in cold sensitivity; and 2) independently of skin cooling, menthol-induced stimulation of TRPM8 triggered wetness perceptions that were greater than those induced by physical dry cooling and by contact with an aqueous cream containing actual moisture. For the first time, we show that the cutaneous cold-sensing TRPM8 channel plays the dual role of cold and wetness sensor in human skin and that this ion channel is a peripheral mediator of human skin wetness perception.

scholarly journals Inulin-type fructans and bone health: state of the art and perspectives in the management of osteoporosis

2005 ◽  
Vol 93 (S1) ◽  
pp. S111-S123 ◽  
Author(s):  
Véronique Coxam
Keyword(s):  
Bone Health ◽  
Health Professionals ◽  
State Of The Art ◽  
Human Subjects ◽  
The Body ◽  
Health State ◽  
Primary Role ◽  
Osteoporosis Prevention ◽  
Optimal Health

If the primary role of diet is to provide sufficient nutrients to meet the metabolic requirements of an individual, there is an emerging rationale to support the hypothesis that, by modulating specific target functions in the body, it can help achieve optimal health. Regarding osteoporosis prevention, since Ca is most likely to be inadequate in terms of dietary intake, every strategy targeting an improvement in Ca absorption is very interesting. Actually, this process may be susceptible to manipulation by fermentable substrates. In this light, inulin-type fructans are very interesting, even if we need to gather more data targeting bone metabolism before health professionals can actively advocate their consumption to prevent senile osteoporosis. Besides targeting the prevention of postmenopausal osteoporosis, inulin-type fructans still remain a source for putative innovative dietary health intervention. Indeed, given in combination with isoflavones, they may have a potential for maintaining or improving the bone mass of human subjects, by modulating the bioavailability of phyto-oestrogens.

scholarly journals Measurements of transmission of radiation through a non-homogeneous medium, viz., the horny layer of the human skin

1931 ◽  
Vol 109 (763) ◽  
pp. 309-318 ◽  
Keyword(s):  
Human Skin ◽  
Direct Action ◽  
Homogeneous Medium ◽  
Living Cells ◽  
The Body ◽  
Optical Beam ◽  
Single Sample ◽  
Horny Layer ◽  
Humid Condition

The experiments and methods to be described represent an attempt to answer with greater accuracy a question to which somewhat divergent answers have already been given. The entire work herein described was done with a single sample of clear, dry, desquamated, human skin (horny layer only), taken from the shoulder of a woman. This sample had been detached from the body for some months, and no attempt had been made to keep it in a more humid condition than that which it would naturally attain in the air of the laboratory ; but we are indebted to Sir Leonard Hill, at whose instance the work was started, for the opinion that the radiation which penetrates this dead horny layer is the deciding factor in the direct action of radiations on the living cells beneath. The writers found that two precautions are essential : first, to secure truly monochromatic radiations ; secondly, to make allowance for the effects due to the scattering of an optical beam when it is passed through such an uneven medium as a piece of skin. The importance of this last precaution has recently been pointed out by Lucas (1931) and Pearson and Jair (1931).

scholarly journals Emission from Human Skin in the Sub THz Frequency Band

2021 ◽  
Author(s):  
Noa Betzalel ◽  
Paul Ben Ishai ◽  
Alexander Puzenko ◽  
Yuri Feldman
Keyword(s):  
Human Skin ◽  
Human Subjects ◽  
Complex Structure ◽  
Skin Surface ◽  
Blackbody Radiation ◽  
The Body ◽  
Electromagnetic Simulation ◽  
Sweat Duct ◽  
Frequency Range ◽  
Body Core

Abstract Recently published Radiometric measurements of human subjects in the frequency range 480-700 GHz, demonstrate the emission of blackbody radiation from the body core, rather than the skin surface. We present a detailed electromagnetic simulation of the dermis and epidermis, taking into account the presence of the sweat duct. This complex structure can be considered as an electromagnetic bio-metamaterial, whereby the layered structure, along with the topology of the sweat duct, reveals a complex interference pattern in the skin. The model is capable of accurately representing the skin greyness factor as a function of frequency and this is confirmed by radiometry of living human skin.

scholarly journals Innervation Territories of Mechano-Insensitive C Nociceptors in Human Skin

2002 ◽  
Vol 88 (4) ◽  
pp. 1859-1866 ◽  
Author(s):  
R. Schmidt ◽  
M. Schmelz ◽  
C. Weidner ◽  
H. O. Handwerker ◽  
H. E. Torebjörk
Keyword(s):  
Human Skin ◽  
Human Subjects ◽  
Receptive Fields ◽  
Healthy Human ◽  
Axon Reflex ◽  
Chemical Substances ◽  
Current Spread ◽  
Healthy Human Subjects ◽  
Median Area

Microneurographic recordings were obtained in the peroneal nerve from 20 mechano-insensitive units (CMi) and six mechano-heat responsive C units (CMH) in healthy human subjects. Their innervation territories in the skin of the leg or foot were assessed by transcutaneous electrical stimulation with a pointed probe at intensities of 10 to 100 mA (0.2 ms) and, when applicable, by mechanical von Frey hair stimulation. Electro-receptive fields (eRFs) of CMH units had a median area of 1.95 cm2 when mapped with 10 mA that coincided approximately with mechano-receptive fields (mRFs) as mapped with a 750-mN von Frey hair. Fifty-milliampere stimuli increased the eRFs to 3.08 cm2 in a concentric manner. This was probably due to current spread since these units are known to have low electrical thresholds. Further increase of the stimulus strength to 70 or 100 mA increased the eRFs only marginally. Mechano-insensitive units had much smaller eRFs (median: 0.35 cm2) than CMH units when mapped with the same pointed probe at 10 mA ( n = 13). The receptive territories consisted of one distinct spot or of several spots separated by distances of more than 1 cm. However, when mapping stimuli of 50 mA were applied, eRFs became continuous and grew to a median area of 5.34 cm2, i.e., larger than those of CMHs. The borders of eRFs of CMi units were significantly more irregular compared with CMH units. A further increase of the stimulus intensity to a maximum of 100 mA only marginally enlarged the eRFs. The CMi units could be activated by heat or chemical substances applied inside the 50-mA eRF, indicating that receptive nerve endings were mapped. Responsiveness to these stimuli was inhomogeneous within the eRFs. It was concluded that innervation territories of CMi units in human skin exceed those of CMH units in size by a factor of approximately 3. The widely branched terminals underlying the large fields are consistent with a role of this nociceptor class in axon reflex flare and preclude a role in exact spatial discrimination of noxious stimuli.

scholarly journals Normalized coefficient of variation (nCV): a method to evaluate circadian clock robustness in population scale data

2021 ◽  
Author(s):  
Gang Wu ◽  
Lauren J. Francey ◽  
Marc D. Ruben ◽  
John B. Hogenesch
Keyword(s):  
Circadian Clock ◽  
Coefficient Of Variation ◽  
Therapeutic Target ◽  
Clock Gene ◽  
Clock Genes ◽  
Population Level ◽  
Circadian System ◽  
Core Feature ◽  
Population Scale ◽  
Scale Data

Robust oscillation of clock genes is a core feature of the circadian system. Relative amplitude (rAMP) measures the robustness of clock gene oscillations, but only works for longitudinal samples. We lack a method for estimating robust oscillations from human samples without labeled time. We show that the normalized coefficient of variation (nCV) is linearly correlated with rAMP, independent of time labels. Using nCV, we found that clock gene oscillations are consistently dampened in tumors compared to non-tumors, suggesting a new therapeutic target in cancer treatment by enhancing clock robustness. nCV can provide a simple measure of the robustness of clock gene oscillations in any population-level dataset.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

Research Recommendations for Applying Vitamin A-Labelled Isotope Dilution Techniques to Improve Human Vitamin A Nutrition

2014 ◽  
Vol 84 (Supplement 1) ◽  
pp. 52-59 ◽  
Author(s):  
Sherry A. Tanumihardjo ◽  
Anura V. Kurpad ◽  
Janet R. Hunt
Keyword(s):  
Public Health ◽  
Vitamin A ◽  
Vitamin A Deficiency ◽  
Human Subjects ◽  
The Body ◽  
Pool Size ◽  
Serum Retinol ◽  
Vitamin A Status ◽  
Status Assessment ◽  
Total Body

The current use of serum retinol concentrations as a measurement of subclinical vitamin A deficiency is unsatisfactory for many reasons. The best technique available for vitamin A status assessment in humans is the measurement of total body pool size. Pool size is measured by the administration of retinol labelled with stable isotopes of carbon or hydrogen that are safe for human subjects, with subsequent measurement of the dilution of the labelled retinol within the body pool. However, the isotope techniques are time-consuming, technically challenging, and relatively expensive. There is also a need to assess different types of tracers and doses, and to establish clear guidelines for the use and interpretation of this method in different populations. Field-friendly improvements are desirable to encourage the application of this technique in developing countries where the need is greatest for monitoring the risk of vitamin A deficiency, the effectiveness of public health interventions, and the potential of hypervitaminosis due to combined supplement and fortification programs. These techniques should be applied to validate other less technical methods of assessing vitamin A deficiency. Another area of public health relevance for this technique is to understand the bioconversion of β-carotene to vitamin A, and its relation to existing vitamin A status, for future dietary diversification programs.

The Role of Computer Modeling in Electrocardiography

1990 ◽  
Vol 29 (04) ◽  
pp. 282-288 ◽  
Author(s):  
A. van Oosterom
Keyword(s):  
Electrical Activity ◽  
Computer Modeling ◽  
Body Surface ◽  
Electrical Current ◽  
The Body ◽  
Volume Conductor ◽  
Current Generator ◽  
Cardiac Electrical Activity ◽  
Source Models

AbstractThis paper introduces some levels at which the computer has been incorporated in the research into the basis of electrocardiography. The emphasis lies on the modeling of the heart as an electrical current generator and of the properties of the body as a volume conductor, both playing a major role in the shaping of the electrocardiographic waveforms recorded at the body surface. It is claimed that the Forward-Problem of electrocardiography is no longer a problem. Several source models of cardiac electrical activity are considered, one of which can be directly interpreted in terms of the underlying electrophysiology (the depolarization sequence of the ventricles). The importance of using tailored rather than textbook geometry in inverse procedures is stressed.

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