Affect Skin Color Research Articles

Native American genetic ancestry and pigmentation allele contributions to skin color in a Caribbean population.

Our interest in the genetic basis of skin color variation between populations led us to seek a Native American population with genetically African admixture but low frequency of European light skin alleles. Analysis of 458 genomes from individuals residing in the Kalinago Territory of the Commonwealth of Dominica showed approximately 55% Native American, 32% African, and 12% European genetic ancestry, the highest Native American genetic ancestry among Caribbean populations to date. Skin pigmentation ranged from 20 to 80 melanin units, averaging 46. Three albino individuals were determined to be homozygous for a causative multi-nucleotide polymorphism OCA2NW273KV contained within a haplotype of African origin; its allele frequency was 0.03 and single allele effect size was -8 melanin units. Derived allele frequencies of SLC24A5A111T and SLC45A2L374F were 0.14 and 0.06, with single allele effect sizes of -6 and -4, respectively. Native American genetic ancestry by itself reduced pigmentation by more than 20 melanin units (range 24-29). The responsible hypopigmenting genetic variants remain to be identified, since none of the published polymorphisms predicted in prior literature to affect skin color in Native Americans caused detectable hypopigmentation in the Kalinago.

Mechanism of skin whitening through San-Bai decoction-induced tyrosinase inhibition and discovery of natural products targeting tyrosinase.

Melanin deposition is the main cause of skin darkening, which can lead to severe physical and psychological distress, necessitating the development of approaches for preserving skin health and fairness. Tyrosinase (TYR) is the rate-limiting enzyme in melanin synthesis, and its activity directly determines the degree of melanin accumulation in the skin, which in turn affects skin color. Currently, TYR inhibitors derived from natural products are widely used for skin whitening. San-Bai decoction (SBD) is effective for skin whitening and softening, but its mechanism of action, efficacy and high efficiency TYR inhibitors for skin whitening remain poorly understood. Here, we employed systems biology and network pharmacology to analyze the active compounds and targets of SBD, using the follow databases: TCMIP, TCMID, and BATMAN-TCM. Construct a molecular network centered on the regulation of TYR by SBD in skin whitening, using STRING database and cytoscape. Enrichment analysis using KOBAS database and ClusterProfiler. Virtual screening of candidate TYR inhibitors using Molecular Operating Environment software and Amber 18 software. SBD may act through tyrosine metabolism, melanogenesis, and other signaling pathways to regulate TYR activity and inhibit melanogenesis. We identified TYR and ESR1 as possible key targets for the whitening effect of SBD and screened out pentagalloylglucose, 1,3,6-tri-O-galloyl-beta-D-glucose, 1,2,4,6-tetragalloylglucose, and liquiritigenin 4',7-diglucoside as inhibitors of TYR, in addition to glycyrrhizic acid, pachymic acid methyl ester, nicotiflorin, gamma-sitosterol, and isoliensinine as inhibitors of ESR1. We also performed virtual drug screening of a library of natural small-molecule compounds (19,505 in total) and screened out lycopsamine, 2-phenylethyl b-D-glucopyranoside, and 6-beta-hydroxyhyoscyamine as inhibitors of TYR. We identified natural compounds with the potential for skin whitening through inhibition of TYR, thus advancing research on SBD and its applications.

How Skin Color Depends on Tissue Oxygenation.

Skin color is essential to skin and wound assessment as it brings valuable information about skin physiology and pathology. An approach, which can help deconvolute and isolate various mechanisms affecting skin color, could be helpful to drive the remote photoplethysmography (rPPG) utility beyond its current applications. The present work aims to create a simple analytical framework that links skin color with blood oxygenation and perfusion. The model consists of two parts. First, the model's core connects changes in tissue chromophore concentrations with changes in tissue reflectance. In the second step, the tissue reflectance is convoluted with the response curves of a sensor (tristimulus response in the case of the human eye) and the light source's spectrum. The model allows linking changes in blood oxygenation and perfusion with changes in skin color. The model can be helpful for the interpretation of the amplitudes of various components of the rPPG signal.

How does captivity affect skin colour reflectance of golden mantella frogs?

Coloration is an important trait for social communication in amphibians, being used in intra- and intersexual signalling to express information about individual body condition and health state, amongst other things. The striking colour pattern exhibited by some anuran species are also used in “aposematic” signals to advertise unpalatability to predators. The aim of this study was to investigate how the captive environment affects the colour of golden mantella frogs by comparing captive reared frogs with wild conspecifics. A USB-2000 portable diode-array spectrometer and a xenon strobe light source were used to perform spectrophotometric measurements on captive and wild populations. Hue, chroma and brightness of skin colour were analysed as well as body condition using the scaled mass index. Analyses showed variation among populations, but significant differences were only found between captive and wild populations. Generalised linear mixed models were used to evaluate the effects of body condition on colour variation and showed that animals with lower body condition from one captive population had significantly different coloration than their wild counterparts. Importantly, one captive population was not greatly different in coloration from their wild counterparts – demonstrating that this problem is not inevitable in captivity. These results can have important implications for reintroduction programmes.

The Hydrothermal Treatment Associated with Calcium Chloride Improve Banana cv. ‘Prata Gorutuba’ Quality Modulating Primary Metabolism

The temperature is one of the most used techniques to maintain fruit quality over long time storage and consequently the fruit respiratory metabolism is directly influenced. The combined use of CaCl2 and hydrothermal treatment can be an important alternative to improve banana fruit quality and influences the ratio starch/sugar and consequently quality traits. Based on the hypothesis the calcium and hydrothermal works synergistically modulating banana primary metabolism and skin color changes. The starch content and chrome parameters were kept in higher values at 2% e 3% (w/v) of CaCl2. However, the fruit storage at control condition have shown lower fresh weight loss (%), followed by total soluble solids and sugars content. In addition, our study showed that, fruit firmness, titratable acidity, skin brightness and hue angle were not significantly influenced by the treatments. In the same vein, banana fruits when treated only by hydrothermal treatment maintained better postharvest quality trait when compared to the fruits of the hydrothermal treatment associated with calcium chloride. The hydrothermal treatment when together with CaCl2 cans influences in the banana fruit quality affecting skin color and primary metabolism such as sugar and starch content.

Cooperative effects of pre-harvest calcium and gibberellic acid on tissue calcium content, quality attributes, and in relation to postharvest disorders of late-maturing sweet cherry

Six Ca(NO3)2 sprays at 0.3% and 0.6% from pit hardening (PH) to 1 week before harvest (1WBH) most effectively increased Ca uptake in sweet cherry (Prunus avium). Low concentration (<0.3%) did not affect the absorption of Ca; high concentration (> 1.6%) caused burning of leaf margins. Fruit treated with Ca had greater fruit firmness (FF), soluble solids content (SSC) and titratable acidity (TA) and fewer disorders than untreated fruit while retaining marketable color and size. A single, low concentration of GA3 combined with Ca sprays enhanced Ca uptake, cracking resistance, and FF without delaying maturation. When Ca plus GA3 sprays were reduced to four times, Ca uptake was retarded, but had an equal or greater benefit than Ca sprays alone. The 5-d harvest delay in combination-treated fruit did not affect skin color, but these fruit had reduced Ca levels at harvest and displayed stem browning after storage.

Analysis of the influence of collagen fibres in the dermis on skin optical reflectance by Monte Carlo simulation in a nine-layered skin model.

Collagen fibres in the dermis play an important structural role in the skin. Age-related changes to these fibres cause wrinkles and slackness of facial skin. However, it is not clear how dermal collagen fibres affect skin colour. The purpose of this study was to clarify the influence of altered collagen fibres on skin colour, using both experimental measurement of fibre density and Monte Carlo simulations in an optical model of skin. Reflection spectra were measured from the cheeks of 12 Japanese women (22-65years old) by spectral colorimeter. Two-dimensional autocorrelation functions were calculated from second harmonics generation (SHG) images acquired from the same locations and used to calculate collagen density indices. Monte Carlo simulations of light reflectance by skin were performed using a nine-layered model that precisely imitates skin structure. The relationship between dermal collagen fibre density and skin reflection spectra was analysed. A positive correlation was found between collagen density and skin brightness, as measured by the colour value, L* (using the L*a*b* colour space). In addition, collagen density showed a strong inverse correlation with age and with the optical absorption of dermis. The Monte Carlo simulations showed that the reflection spectrum of skin changes when the scattering coefficient of the dermis is altered. These changes were the same for simulated and experimentally measured reflection spectra. When collagen fibre density in the upper dermis is decreased with age, skin colour becomes less bright because light scattering in the skin is decreased.

A functional single nucleotide polymorphism in the tyrosinase gene promoter affects skin color and transcription activity in the black-boned chicken

The tyrosinase (TYR) gene is the major melanogenesis-related gene for skin (fur) or plumage color in mammals and birds. Genetic variation in the promoter region of a gene may affect gene expression and phenotypes. This study compared the TYR promoter region between pooled DNA (n = 8) of chickens (Gallus gallus) with black and white skin using direct sequencing. The single nucleotide polymorphism (SNP) c.-2228A>T was found to have the opposite allele distribution in the two groups. The results of genotyping in a larger population (n = 188) revealed that SNP c.-2228A>T was associated with the skin color of the black-boned chicken. Individuals with genotypes AA and AT had greater TYR expression than those with genotype TT. A luciferase assay of the promoter activity revealed that genotype AA had greater activity than genotype TT. Transcription factor binding site analyses showed that the c.-2228A allele has a putative binding site for transcription factor AT-rich interaction domain 3a (Arid3a), while the c.-2228T allele has sites for GS homeobox 2 (GSX2), homeobox D9 (Hoxd9), and mix paired-like homeobox (MIXL1). We concluded that the TYR promoter polymorphism affects skin color. SNP c.-2228A>T could be used as a genetic marker for marker-assisted selection of skin color in the black-boned chicken.

큰비쑥 추출물의 멜라닌 생성 억제 효과

Melanin is one of the most important factors affecting skin color. Melanogenesis is the bioprocess of melanin production by melanocytes in the skin and hair follicles and is mediated by several enzymes, such as tyrosinase, tyrosinase related protein (TRP)-1, and TRP-2, MITF. In this study, we investigated the effect of Artemisia fukudo Makino extracts on tyrosinase activity and melanin production as natural products of whitening functional cosmetics. Melanin content in murine B16F10 melanoma cells were decreased by Artemisia fukudo Makino extracts in a dose-dependently. In addition, the inhibition of tyrosinase activity of Artemisia fukudo Makino extracts showed to decrease tyrosinase activity as the concentration of α-MSH was increased. Furthermore, western blot analysis revealed that Artemisia fukudo Makino extracts significantly downregulated the expression of tyrosinase, TRP-1 which treat of α-MSH–induced melanogenesis in murine B16F10 melanoma cells. As a result, Artemisia fukudo Makino extract showed functionalities as an effective whitening agent to inhibit melanin formation.

173 A study on skin properties related to chronic psychological stress

These days many people live under a lot of stress in everyday life. According to many studies, chronic or long-term stress has bad effects on health. Several studies have founded that the skin barrier function is weakened by stress. However, few studies have shown how stress affects the skin except skin barrier. The objective of this study is to determine skin properties related on chronic stress. Three surveys confirming stress were conducted on 60 women in their age 40s. (Three surveys : Korean-translated Brief Encounter Psychosocial Instrument (BEPSI-K), Cognitive Stress Response Scale (CSRS), Stress Questionnaire for Korean National Health and Nutrition Examination Survey (KNHANES): short form) The subjects were identified the two groups by three survey responses. A clinical research was conducted on 28 subjects (stress group N=14, non-stress group N=14) who agree to experimentation. The measurement parameters were hydration, skin color, elasticity, trans-epidermal water loss (TEWL), gloss, transparency, wrinkles. The statistical significance was determined at P < 0.05. The elasticity and skin brightness (L value, V value) of non-stress group are significantly higher than stress group. And the pores area and transparency of non-stress group are lower than stress group. The hydration, TEWL and wrinkles have no significant differences between stress group and non-stress group. We examined the beauty habits and lifestyles through the survey. The stress group responded that they have more sleep disorder than the non-stress group significantly. There was no difference in beauty habits between the stress group and non-stress group except sleep disorder. In conclusion, psychological stress affects the skin especially affects skin color, elasticity, pores, and transparency. These differences were not due to beauty habits.

Long‐term changes in Japanese women's facial skin color

AbstractIt has been suggested that skin color changes not only with advancing age but also with the times. The purpose of this study was to investigate changes in Japanese women's facial skin color over 25 years, as well as the changes in skin pigmentation that affect skin color. First, skin color changes in terms of Munsell color values were investigated. A total of 3181 Japanese women residing in the greater Tokyo area were enrolled, and datasets were collected using spectrophotometers, designated as the 1991, 2001, 2005, and 2015 data. The mean Munsell hue, value, and chroma were calculated for each measurement year. Next, the concentrations of melanin and hemoglobin were calculated from spectral data, to investigate changes in skin pigmentations. Finally, Monte Carlo simulations were performed to verify that the suggested changes in skin pigmentations brought about skin color changes. As a result, skin color significantly changed toward high lightness, low saturation, and high yellowness from the 1991 data to the 2001 data. From the 2005 to 2015 data, the skin color distribution shifted toward lower saturation and increased redness. In addition, the concentration of hemoglobin decreased significantly from the 1991 data to the 2001 data, while the melanin concentration decreased significantly from the 2005 data to the 2015 data.

Polymeric peptide pigments with sequence-encoded properties.

Melanins are a family of heterogeneous polymeric pigments that provide ultraviolet (UV) light protection, structural support, coloration, and free radical scavenging. Formed by oxidative oligomerization of catecholic small molecules, the physical properties of melanins are influenced by covalent and noncovalent disorder. We report the use of tyrosine-containing tripeptides as tunable precursors for polymeric pigments. In these structures, phenols are presented in a (supra-)molecular context dictated by the positions of the amino acids in the peptide sequence. Oxidative polymerization can be tuned in a sequence-dependent manner, resulting in peptide sequence-encoded properties such as UV absorbance, morphology, coloration, and electrochemical properties over a considerable range. Short peptides have low barriers to application and can be easily scaled, suggesting near-term applications in cosmetics and biomedicine.

Impact of fresh fruit smoothie consumption on apparent health of Asian faces

Abstract Skin carotenoid coloration has been proposed as a valid cue to health in humans, reflecting fruit and vegetable intake, and enhancing apparent health. Supplementation with a carotenoid-rich fruit and vegetable smoothie affects skin color, but it is not known if this skin color change enhances healthy appearance. In three experiments, we examine the effects of skin color change induced by supplementation with a carotenoid-rich fruit smoothie (25mg carotenoids/d) on the apparent health of Malaysian Chinese faces. In experiment 1, observers were asked to identify the healthier looking of pairs of photographs of the same subject taken pre- and post-supplementation (or pre- and post-placebo), choosing the pre-supplementation (or pre-placebo) images. When confounding due to facial expression was eliminated in experiment 2, observers showed no preference for unmodified pre-supplementation photograph or the same image with skin color manipulated to simulate a level of smoothie-induced color change associated with 4weeks of supplementation. In experiment 3, observers manipulated the skin color of face photographs along the smoothie-induced color change axis to optimize healthy appearance. Observers chose to induce a color change approximately equivalent to one third of the change induced by daily consumption of our carotenoid rich smoothie. This suggests that the skin color change induced by the supplementation enhanced apparent facial health, however the dose and duration of the supplementation overshot the optimal healthy-looking color of Malaysian Chinese skin. This suggests that there is an optimal carotenoid color for healthy appearance, and that this optimal level may be constrained by preferences for averageness, by the association between very yellow skin and ill health, or by negative health impacts of very high doses of carotenoids.

마우스 흑색종세포에서 Purpurogallin의 멜라닌 생성 억제 효과

Melanin is one of the most important factors affecting skin color. Melanogenesis is the bioprocess of melanin production by melanocytes in the skin and hair follicles and is mediated by several enzymes, such as tyrosinase, tyrosinase related protein (TRP)-1, and TRP-2. Convenient enzymatic transformation of the simple phenol pyrogallol with polyphenol oxidase originating from pear to an oxidative product, purpurogallin, was efficient. The structure of the pyrogallol oxidation product was identified on the basis of spectroscopic methods. The biotransformation product purpurogallin showed significant inhibitory effects against both melanin synthesis and tyrosinase activity in a dose-dependent manner in B16 melanoma cells. In addition, purpurogallin significantly attenuated melanin production by inhibiting TRP-1, and TRP-2 expression through modulation of their corresponding transcription factors, and microphthalamia- associated transcription factor in B16 cells. Consequently, purpurogallin derived from convenient enzymatic transformation of pyrogallol might be a beneficial material for reducing skin hyperpigmentation.

Allele-specific transcriptional regulation of IRF4 in melanocytes is mediated by chromatin looping of the intronic rs12203592 enhancer to the IRF4 promoter.

The majority of significant single-nucleotide polymorphisms (SNPs) identified with genome-wide association studies are located in non-coding regions of the genome; it is therefore possible that they are involved in transcriptional regulation of a nearby gene rather than affecting an encoded protein's function. Previously, it was demonstrated that the SNP rs12203592, located in intron 4 of the IRF4 gene, is strongly associated with human skin pigmentation and modulates an enhancer element that controls expression of IRF4. In our study, we investigated the allele-specific effect of rs12203592 on IRF4 expression in epidermal skin samples and in melanocytic cells from donors of different skin color. We focused on the characteristics and activity of the enhancer, and on long-range chromatin interactions in melanocytic cells homozygous and heterozygous for rs12203592. We found that, irrespective of the trans-activating environment, IRF4 transcription is strongly correlated with the allelic status of rs12203592, the activity of the rs12203592 enhancer and that the chromatin features depend on the rs12203592 genotype. Furthermore, we demonstrate that the rs12203592 enhancer physically interacts with the IRF4 promoter through an allele-dependent chromatin loop, and suggest that subsequent allele-specific activation of IRF4 transcription is stabilized by another allele-specific loop from the rs12203592 enhancer to an additional regulatory element in IRF4. We conclude that the non-coding SNP rs12203592 is located in a regulatory region and affects a wide range of enhancer characteristics, resulting into modulation of the enhancer's activity, its interaction with the IRF4 promoter and subsequent allele-specific transcription of IRF4. Our findings provide another example of a non-coding SNP affecting skin color by modulating enhancer-mediated transcriptional regulation.

The Pituitary Gland of the European Eel Reveals Massive Expression of Genes Involved in the Melanocortin System

Hormones secreted from the pituitary gland regulate important processes such as development, growth and metabolism, reproduction, water balance, and body pigmentation. Synthesis and secretion of pituitary hormones are regulated by different factors from the hypothalamus, but also through feedback mechanisms from peripheral organs, and from the pituitary itself. In the European eel extensive attention has been directed towards understanding the different components of the brain-pituitary-gonad axis, but little is known about the regulation of upstream processes in the pituitary gland. In order to gain a broader mechanistic understanding of the eel pituitary gland, we have performed RNA-seq transcriptome profiling of the pituitary of prepubertal female silver eels. RNA-seq reads generated on the Illumina platform were mapped to the recently assembled European eel genome. The most abundant transcript in the eel pituitary codes for pro-opiomelanocortin, the precursor for hormones of the melanocortin system. Several genes putatively involved in downstream processing of pro-opiomelanocortin were manually annotated, and were found to be highly expressed, both by RNA-seq and by qPCR. The melanocortin system, which affects skin color, energy homeostasis and in other teleosts interacts with the reproductive system, has so far received limited attention in eels. However, since up to one third of the silver eel pituitary’s mRNA pool encodes pro-opiomelanocortin, our results indicate that control of the melanocortin system is a major function of the eel pituitary.

Appealing to vanity: could potential appearance improvement motivate fruit and vegetable consumption?

Fruit and vegetable consumption is inadequate among adults in the United States; this contributes to preventable morbidity and mortality. More effective dietary intervention strategies are needed. Recently, interventions that advertise the consequences of behavior for appearance have been successful in modifying sun-exposure habits and tobacco use. Such an approach might also facilitate dietary improvement. Consumption of carotenoid-rich fruit and vegetables positively affects skin color, which influences perceptions of health and attractiveness, and promoting such an effect may motivate target audiences to increase consumption of this important food group. This approach represents a novel direction for the field and is potentially suitable for cost-effective, population-level dissemination through the visual media.

MC1R Gene Polymorphism Affects Skin Color and Phenotypic Features Related to Sun Sensitivity in a Population of French Adult Women

The melanocortin-1 receptor (MC1R) gene is known to play a major role in skin and hair pigmentation and to be highly polymorphic in Caucasians. This study was performed to investigate the relationships between MC1R gene polymorphisms and skin color in a large sample of French middle-aged Caucasian women. The codons 60 to 265 and the codon 294 of the MC1R gene were sequenced in 488 women. The skin color was measured on the inner side of the forearm using a spectrophotometric instrument. Fifteen variants were identified: Arg151Cys, Arg160Trp, Arg142His, Asp294His, Ile155Thr, Asp84Glu, Val60Leu, Val92Met, Arg163Gln, Ser83Pro, Thr95Met, Pro256Ser, Val265Ile, Ala166Ala and Gln233Gln. Women carrying Arg151Cys, Asp294His, Arg160Trp and Asp84Glu variants had a significantly higher reflectance in the red region, which indicates a lower level of functional melanin. This association was the most pronounced for women carrying Asp84Glu. In contrast, no significant difference was observed for other variants. Moreover, associations between MC1R polymorphisms and the risks of experiencing sunburn and of having freckles were found independently of skin color. Our findings support the hypothesis that MC1R polymorphisms do not necessarily alter the skin color but should sensitize the skin to UV-induced DNA damage.

An oral nutraceutical containing antioxidants, minerals and glycosaminoglycans improves skin roughness and fine wrinkles

Various nutraceuticals (dietary supplements) are claimed to have cutaneous antiageing properties, however, there are a limited number of research studies supporting these claims. The objective of this research was to study the effectiveness of an oral nutraceutical containing antioxidants, minerals and glycosaminoglycans on cutaneous ageing. In this double-blind, placebo-controlled trial, 60 women aged 35-60 years were randomized to receive oral dietary supplement (n = 30) or placebo (n = 30), once daily for 12 weeks. The depth of skin roughness and fine wrinkles were measured using surface evaluation of skin parameters for living skin (Visioscan) at baseline, and at the 4, 8 and 12 weeks of treatment. Surface evaluation using a replica film (Visiometer) at baseline and at the 12th week of treatment was also carried out. Statistical differences in objective skin improvement were assessed by the independent t-test. The volunteers' satisfaction was tested using the chi-squared test. The baseline depth of skin roughness and fine wrinkles in the treatment group and the placebo group were 100.5 and 100 mum, respectively. At the end of the study, the depth of skin roughness and fine wrinkles in the treatment group showed a 21.2% improvement, whereas improvement in the control group was 1.7%. This difference was statistically significant (P < 0.001). With regard to the volunteers' satisfaction, there was no statistically significant decrease in the homogenization of skin colour, however, a statistically significant reduction in pore size and depth of skin roughness and fine wrinkles were observed (P < 0.05). No side effects were noted throughout the study. The oral dietary supplement containing antioxidants, minerals and glycosaminoglycans improved skin roughness and fine wrinkles but did not affect skin colour change in female volunteers.

Physiological factors that regulate skin pigmentation

More than 150 genes have been identified that affect skin color either directly or indirectly, and we review current understanding of physiological factors that regulate skin pigmentation. We focus on melanosome biogenesis, transport and transfer, melanogenic regulators in melanocytes, and factors derived from keratinocytes, fibroblasts, endothelial cells, hormones, inflammatory cells, and nerves. Enzymatic components of melanosomes include tyrosinase, tyrosinase-related protein 1, and dopachrome tautomerase, which depend on the functions of OA1, P, MATP, ATP7A, and BLOC-1 to synthesize eumelanins and pheomelanins. The main structural component of melanosomes is Pmel17/gp100/Silv, whose sorting involves adaptor protein 1A (AP1A), AP1B, AP2, and spectrin, as well as a chaperone-like component, MART-1. During their maturation, melanosomes move from the perinuclear area toward the plasma membrane. Microtubules, dynein, kinesin, actin filaments, Rab27a, melanophilin, myosin Va, and Slp2-a are involved in melanosome transport. Foxn1 and p53 up-regulate skin pigmentation via bFGF and POMC derivatives including alpha-MSH and ACTH, respectively. Other critical factors that affect skin pigmentation include MC1R, CREB, ASP, MITF, PAX3, SOX9/10, LEF-1/TCF, PAR-2, DKK1, SCF, HGF, GM-CSF, endothelin-1, prostaglandins, leukotrienes, thromboxanes, neurotrophins, and neuropeptides. UV radiation up-regulates most factors that increase melanogenesis. Further studies will elucidate the currently unknown functions of many other pigment genes/proteins. (c) 2009 International Union of Biochemistry and Molecular Biology, Inc.