Hair Formation Research Articles

Virilization Secondary to an Ovarian Leydig Cell Tumor

A 60-year-old female presented with a three-year history of virilizing symptoms including facial hirsutism and deepening of voice. Her medical history was significant for renal transplantation with immunosuppressive therapy consisting of mycophenolate, cyclosporine, and low-dose prednisone. She was noted to have temporal balding and darkly pigmented terminal hair on the upper lip, cheeks, chin, shoulders, and sternum. Pelvic examination revealed clitoromegaly. Menarche occurred at age 12 with regular menstrual cycles until menopause which occurred at age 50. She had two pregnancies: a miscarriage followed by a successful pregnancy.Labs revealed an elevated total testosterone of 530 ng/dL (< 60 ng/dL), free testosterone 14.8 ng/dL (<0.87 ng/dL), androstenedione 2140 ng/dL (<200 ng/dL), and 17-hydroxyprogesterone 704 ng/dL (<285 ng/dL). LH, FSH, and estradiol were inappropriately normal in this post-menopausal female. Prolactin, TSH, DHEA-S, IGF-1 were within normal limits. Transvaginal ultrasound found a 2 cm hypoechoic right ovarian mass which was confirmed on MRI. MRI also revealed a 5 mm right adrenal nodule. Tumor markers including CA-125, Inhibin A, Inhibin B, HCG, and AFP were within normal limits. Dexamethasone suppression testing did not lower the testosterone level. 17-hydroxyprogesterone level after cosyntropin stimulation testing was 704 ng/dL (<1000 ng/dL). The patient underwent laparoscopic bilateral oophorectomy and salpingectomy, pelvic washout and omental biopsy. Pathology was consistent with a benign Leydig cell tumor. Following oophorectomy there was complete normalization of the total testosterone level (15 ng/dL, n< 60 ng/dL).A thorough history and physical exam is vital in determining the cause of hirsutism. Medications, including over-the-counter and herbal formulations should be carefully reviewed. Although cyclosporine has been associated with hirsutism, patients typically present with vellus hair formation in the affected areas rather than darkly pigmented terminal hair. In this case, hirsutism progressively worsened following menopause and physical examination was significant for virilization. Hirsutism in a combination with virilization is typically neoplastic in nature. Endogenous androgen production can originate from either the adrenal glands or ovaries. In our patient, with workup showing both ovarian and adrenal as potential sources of endogenous androgen production, an adrenal cause was excluded due to a normal DHEA-S level at baseline and a lack of suppression of testosterone after dexamethasone suppression testing. As a result, the source was localized to the ovary. While excessive androgen production resulting in virilization is seen with ovarian tumors, Leydig stromal cell tumors are extremely rare and account for less than 0.1% of all ovarian tumors.

Reactive Oxygen Species Link Gene Regulatory Networks During Arabidopsis Root Development.

Plant development under altered nutritional status and environmental conditions and during attack from invaders is highly regulated by plant hormones at the molecular level by various signaling pathways. Previously, reactive oxygen species (ROS) were believed to be harmful as they cause oxidative damage to cells; however, in the last decade, the essential role of ROS as signaling molecules regulating plant growth has been revealed. Plant roots accumulate relatively high levels of ROS, and thus, maintaining ROS homeostasis, which has been shown to regulate the balance between cell proliferation and differentiation at the root tip, is important for proper root growth. However, when the balance is disturbed, plants are unable to respond to the changes in the surrounding conditions and cannot grow and survive. Moreover, ROS control cell expansion and cell differentiation processes such as root hair formation and lateral root development. In these processes, the transcription factor-mediated gene expression network is important downstream of ROS. Although ROS can independently regulate root growth to some extent, a complex crosstalk occurs between ROS and other signaling molecules. Hormone signals are known to regulate root growth, and ROS are thought to merge with these signals. In fact, the crosstalk between ROS and these hormones has been elucidated, and the central transcription factors that act as a hub between these signals have been identified. In addition, ROS are known to act as important signaling factors in plant immune responses; however, how they also regulate plant growth is not clear. Recent studies have strongly indicated that ROS link these two events. In this review, we describe and discuss the role of ROS signaling in root development, with a particular focus on transcriptional regulation. We also summarize the crosstalk with other signals and discuss the importance of ROS as signaling molecules for plant root development.

707 Hypoxia induced Multipotent Stem Cell-Secreted Proteins Induce Hair Growth in a Phase 1a/2b trial in Male Pattern Baldness

A Phase 1b/2a clinical trial was performed to study the safety and efficacy of a bioengineered human cell-derived formulation, termed Hair Stimulating Complex (HSC), in stimulating hair growth and preventing hair loss in subjects with male pattern baldness. HSC contains naturally secreted growth factors known to be important in hair growth, including follistatin, KGF, VEGF, PLGF, HGF, and angiogenin. These growth factors are key to stimulating the hair follicle stem cells, supporting keratinocyte migration into the follicle to result in new hair formation, and promoting angiogenesis to supply increased nutrients to support the highly metabolically active anagen phase. Several ELISA and cell-based assays, including a human outer root sheath assay, are used to release the clinical product. The study was a double-blind, 2:1 randomized, single center trial in 36 subjects with Norwood Hamilton scores of 3V, 4, and 5. All subjects tolerated well the twenty 0.1cc intradermal injections, distributed between the vertex and temporal regions, administered at baseline, 6, and 12 weeks, with no signs of a serious adverse reaction reported. Canfield image analysis of treated sites were taken at baseline and 18 weeks. At the 18-week time point, 75% of the HSC subjects responded to treatment and showed new hair growth and a cessation in hair loss whereas 63% of the control subjects continued to lose hair. Canfield imaging at week 26 will assess total hair count numbers as well as vellus, non-vellus hairs and hair thickness. These results clearly demonstrate the safety and efficacy of intradermal injections of HSC in subjects with androgenetic alopecia and support initiating a larger phase 2 dosing study.

Length variation in short tandem repeats affects gene expression in natural populations of Arabidopsis thaliana.

The genetic basis for the fine-tuned regulation of gene expression is complex and ultimately influences the phenotype and thus the local adaptation of natural populations. Short tandem repeats (STRs) consisting of repetitive DNA motifs have been shown to regulate gene expression. STRs are variable in length within a population and serve as a heritable, but semi-reversible, reservoir of standing genetic variation. For sessile organisms, such as plants, STRs could be of major importance in fine-tuning gene expression as a response to a shifting local environment. Here, we used a transcriptome dataset from natural accessions of Arabidopsis thaliana to investigate population-wide gene expression patterns in light of genome-wide STR variation. We empirically modeled gene expression as a response to the STR length within and around the gene and demonstrated that an association between gene expression and STR length variation is unequivocally present in the sampled population. To support our model, we explored the promoter activity in a transcriptional regulator involved in root hair formation and provided experimentally determined causality between coding sequence length variation and promoter activity. Our results support a general link between gene expression variation and STR length variation in A. thaliana.

De novo filament formation by human hair keratins K85 and K35 follows a filament development pattern distinct from cytokeratin filament networks.

In human hair follicles, the hair‐forming cells express 16 hair keratin genes depending on the differentiation stages. K85 and K35 are the first hair keratins expressed in cortical cells at the early stage of the differentiation. Two types of mutations in the gene encoding K85 are associated with ectodermal dysplasia of hair and nail type. Here, we transfected cultured SW‐13 cells with human K85 and K35 genes and characterized filament formation. The K85–K35 pair formed short filaments in the cytoplasm, which gradually elongated and became thicker and entangled around the nucleus, indicating that K85–K35 promotes lateral association of short intermediate filaments (IFs) into bundles but cannot form IF networks in the cytoplasm. Of the K85 mutations related to ectodermal dysplasia of hair and nail type, a two‐nucleotide (C1448T1449) deletion (delCT) in the protein tail domain of K85 interfered with the K85–K35 filament formation and gave only aggregates, whereas a missense mutation (233A>G) that replaces Arg78 with His (R78H) in the head domain of K85 did not interfere with the filament formation. Transfection of cultured MCF‐7 cells with all the hair keratin gene combinations, K85–K35, K85(R78H)–K35 and K85(delCT)–K35, as well as the individual hair keratin genes, formed well‐developed cytoplasmic IF networks, probably by incorporating into the endogenous cytokeratin IF networks. Thus, the unique de novo assembly properties of the K85–K35 pair might play a key role in the early stage of hair formation.

Cell cycle regulation in human hair follicle dermal papilla cells using nonthermal atmospheric pressure plasma-activated medium.

Nonthermal atmospheric pressure (NAP) plasmas have recently been developed and have been used for wound healing, blood coagulation, and cancer therapy. NAP plasmas can induce either cell proliferation or cell death, depending on the dose. Due to their efficacy and application easily, plasma activated mediums (PAMs) have been used in human cells recently.In atmosphere, NAP plasmas react with molecular content of air such as N2, O2, H2O vapor, etc, and generate a variety of reactive oxygen and nitrogen species. High reactive oxygen species (ROS) levels promote damage of cellular DNA, proteins, and lipids. Such damage can lead to cell-cycle arrest, and cellular death. However, low levels of ROS have been caused an increase in cell cycle progression.Human skin is arranged in 3 layers, including (from top to bottom) the epidermis (and its appendages), the dermis, and the hypodermis. Human dermal papilla cells (DPCs) are located in the middle or even deep part of the dermis. DPCs play a key role in hair regeneration, and a lot of effort have been made to promote DPC hair formation ability. DPC is increased proliferation, delayed senescence, and enhanced hair by depending on the amount of ROS through the NAP-PAM treatment.In this study, we used NAP plasmas to the human hair follicle DPCs exposed from 0 to 20 minutes, so we were investigated the effects of PAM on cell proliferation and cell cycle progression. After NAP-PAM treatment for 24 hours, cell cycle was arrested in the G0/G1 phase. The NAP-PAM-treated human hair follicle DPCs recovered gradually after 48 hours of the treatment compared to the untreated cells.Therefore, this approach offers promising results for further application of NAP-PAM in clinical dermatology. In future, it can be applied clinically in the form of active water that can delay the progression of baldness and alopecia areata.

Transcriptome sequencing analysis of maize roots reveals the effects of substrate and root hair formation in a spatial context

BackgroundPlant roots sense and respond to changes in their soil environment, but conversely contribute to rhizosphere organization through chemical, mechanical and biotic interactions. Transcriptomic profiling of plant roots can be used to assess how the plant adjusts its gene expression in relation to environment, genotype and rhizosphere processes; thus enabling us to achieve a better understanding of root-soil interactions.MethodsWe used a standardized soil column experimental platform to investigate the impact of soil texture (loam, sand) and root hair formation (wildtype, root hair defective rth3 mutant) in a spatial context (three sampling depths) and assessed maize root transcriptomic profiles using next-generation RNA sequencing.ResultsSubstrate induced the largest changes in root gene expression patterns, affecting gene functions related to immunity, stress, growth and water uptake. Genes with column depth-related expression levels were associated with growth and plant defense. The influence of root hairs mainly manifested in differential expression of epidermal cell differentiation and cell wall organization, and defense response-related genes. Substrate type strongly modified the transcriptomic patterns related to column depth and root hair elongation, highlighting the strong impact of soil texture.ConclusionsOur results demonstrate that substrate, sampling depth and plant genotype interactively affect maize gene expression, and suggest feedback processes between the plant, the soil and the microbiome. The obtained results form a foundational basis for the integration and interpretation of future experiments utilizing the same experimental platform.

A literature review on function and regulation mechanism of DKK4.

Dickkopf‐related protein 4 (DKK4) is a member of the dickkopf family and an inhibitor of the Wnt/β‐catenin signalling pathway. This review surveyed the single nucleotide polymorphisms (SNPs), copy number variations (CNVs), hypermethylation, regulation mechanism, correlation with clinicopathological parameters and chemotherapeutic resistance of DKK4. The signal pathways involved in DKK4 mainly include Wnt/β‐catenin pathway and Wnt‐JNK pathway independent β‐catenin. DKK4 expression was upregulated in Renal Cell Carcinoma (RCC), Colorectal Cancer, Gastric Cancer (GC), Non‐small Cell Lung Cancer (NSCLC) and Epithelial Ovarian Cancer (EOC), while downregulated in Hepatocellular Carcinoma (HCC). DKK4 is not only involved in tumour growth, invasion, migration and chemotherapy resistance, but also in osteoblastogenesis and secondary hair or meibomian gland formation. DKK4 has also been linked to schizophrenia.

Features of the morphological structure of plants and biochemical properties of introduced and domestic varieties of Cannabis sativa L.

Purpose. Identifying the features of the seasonal growth rhythm, development of the plants, morphological and biological differences in monoecious introduced and domestic varieties of Cannabis sativa L. in the North-east region of Ukraine.Methods. The research was conducted from 2014 till 2019. The following research methods were employed: field (phenological observations, sampling for laboratory analysis), microscopic (study of the morphological structure of glandular and cystolithic hairs on vegetative and generative organs, determination of the size and density of hair formation), laboratory and analytical (determination of the content of cannabinoid substances by thin layer and gas-liquid chromatography), biomorphological me­thods (analysis of morphological characteristics of plants). Chemical analysis for the content of cannabinoid substan­ces was carried out in the laboratory of the breeding and seed production department of the Institute of Bast Crops of the NAAS of Ukraine (Glukhiv, 2014–2019). The content of neutral substances [cannabinol (CBN), cannabidiol (CBD), tetrahydrocannabinol (THC)] and acids (CBDA, THCA) was determined by using a thin layer chromatography (TLC) and gas-liquid chromatography (GLC) methods. For the study, 11 monoecious varieties of C. sativa: ‘YuSO 1’, ‘YuSO 31’, ‘Hliana’, ‘Viktoriia’, ‘Hlesiia’, ‘Hlukhivskyi 46’, ‘Hlukhivski 51’, ‘Zoloto­niski 15’ and 3 introduced varieties: ‘Fedora 17’, ‘Felina 32’, ‘Futura 77’ (France) which differed among themselves in morphological, biological, genetic, ecological-geographical and economically valuable characteristics were selected.Results. Biological and morphological characteristics of modern monoecious varieties of C. sativa were investigated depending on the ecological and geographical zones of origin, conditions of the growing season and the stage of ontogenesis. The functional interdependence between the formation of specialized excretory structures and the content of cannabinoid substances in plants of different varieties of C. sa­tiva was revealed. The following promising varieties of C. sativa in a ration of ((THC + CBN) ≤ CBD) point the possibility to use them as the source material for creating the medicinal varie­ties of plants with a high content of CBD.Conclusions. Nowadays C. sativa is the main source of phyto material for industrial production of natural CBD. In recent years, high-yielding varieties of C. sativa have been created, which, together with high commercially valuable traits, did not contain psychoactive THC and had an insignificant amount of CBD. The results of the research indicated the features of the seasonal growth rhythm, development of the plants and the morphological and biological features of modern monoecious introduced and domestic varieties of C. sativa in the North-east region of Ukraine. The low correlation between the content of cannabinoid substances and their acids in varieties, which are cha­racterized by the low content of cannabinoid compounds was established. According to the developed own classification (THC + KBN): CBD, varieties with a predominant CBD content ‘Hlukhivskyi 46’, ‘Zolotoniski 15’, ‘Hliana’ which are of significant medicinal value were identified.

Electric stimulation promotes growth, mineral uptake, and antioxidant accumulation in kale (Brassica oleracea var. acephala)

Several studies have demonstrated that electric treatment has a positive effect, respectively, on germination, root growth and post-harvest quality. Nevertheless, there is still a lack of research on the effect of electric treatment on growth characteristics and quality of whole plants. Here, we explored the effect of electric fields on two cultivars of kale (Brassica oleracea var. acephala). Three levels of electric current (10, 50, and 100 mA) were applied to the nutrient solution of hydroponically grown plants for three weeks. Kale plants subjected to the electric fields, particularly 50 mA, had higher fresh and dry weights than the control. The absence of an electric field in a Faraday cage caused a significant decrease in shoot and root growth compared with the natural electric field (control). Electrostimulation enhanced nutrient uptake by activating root hair formation and active ion transport. Plants grown under 50 mA contained 72% more calcium, 57% more total phenolic compounds, and had a 70% greater antioxidant capacity than the control. This work provides foundational information regarding the effects of electrical stimulus on plants, which could enable the development of innovative culture technologies to improve crop yields and quality.

A relook into plant wilting: observational evidence based on unsaturated soil\u2013plant-photosynthesis interaction

Permanent wilting point (PWP) is generally used to ascertain plant resistance against abiotic drought stress and designated as the soil water content (θ) corresponding to soil suction (ψ) at 1500 kPa obtained from the soil water retention curve. Determination of PWP based on only pre-assumed ψ may not represent true wilting condition for soils with contrasting water retention abilities. In addition to ψ, there is a need to explore significance of additional plant parameters (i.e., stomatal conductance and photosynthetic status) in determining PWP. This study introduces a new framework for determining PWP by integrating plant leaf response and ψ during drought. Axonopus compressus were grown in two distinct textured soils (clayey loam and silty sand), after which drought was initiated till wilting. Thereafter, ψ and θ within the root zone were measured along with corresponding leaf stomatal conductance and photosynthetic status. It was found that coarse textured silty sand causes wilting at much lower ψ (≈ 300 kPa) than clayey loam (≈ 1600 kPa). Plant response to drought was dependent on the relative porosity and mineralogy of the soil, which governs the ease at which roots can grow, assimilate soil O2, and uptake water. For clay loam, the held water within the soil matrix does not facilitate easy root water uptake by relatively coarse root morphology. Contrastingly, fine root hair formation in silty sand facilitated higher plant water uptake and doubled the plant survival time.

Uncoupling root hair formation and defence activation from growth inhibition in response to damage-associated Pep peptides in Arabidopsis thaliana.

In Arabidopsis thaliana, PROPEPs and their derived elicitor-active Pep epitopes provide damage-associated molecular patterns (DAMPs), which trigger defence responses through cell-surface receptors PEPR1 and PEPR2. In addition, Pep peptides induce root growth inhibition and root hair formation, however their relationships and coordinating mechanisms are poorly understood. Here, we reveal that Pep1-mediated root hair formation requires PEPR-associated kinases BAK1/BKK1 and BIK1/PBL1, ethylene, auxin and root hair differentiation regulators, in addition to PEPR2. Our analysis on 69 accessions unravels intraspecies variations in Pep1-induced root hair formation and growth inhibition. The absence of a positive correlation between the two traits suggests their separate regulation and diversification in natural populations of A. thaliana. Restricted PEPR2 expression to certain root tissues is sufficient to induce root hair formation and growth inhibition in response to Pep1, indicating the capacity of non-cell-autonomous receptor signalling in different root tissues. Of particular note, root hair cell-specific PEPR2 expression uncouples defence activation from root growth inhibition and root hair formation, suggesting a unique property of root hairs in root defence activation following Pep1 recognition.

Multi-Walled Carbon Nanotubes Can Promote Brassica napus L. and Arabidopsis thaliana L. Root Hair Development through Nitric Oxide and Ethylene Pathways.

Here, we report that multi-walled carbon nanotubes (MWCNTs) can promote plant root hair growth in the species analyzed in this study; however, low and excessive concentrations of MWCNTs had no significant effect or even an inhibiting influence. Further results show that MWCNTs can enter rapeseed root cells. Meanwhile, nitrate reductase (NR)-dependent nitric oxide (NO) and ethylene syntheses, as well as root hair formation, were significantly stimulated by MWCNTs. Transcription of root hair growth-related genes were also modulated. The above responses were sensitive to the removal of endogenous NO or ethylene with a scavenger of NO or NO/ethylene synthesis inhibitors. Pharmacological and molecular evidence suggested that ethylene might act downstream of NR-dependent NO in MWCNTs-induced root hair morphogenesis. Genetic evidence in Arabidopsis further revealed that MWCNTs-triggered root hair growth was abolished in ethylene-insensitive mutants ein2-5 and ein3-1, and NR mutant nia1/2, but not in noa1 mutant. Further data placed NO synthesis linearly before ethylene production in root hair development triggered by MWCNTs. The above findings thus provide some insights into the molecular mechanism underlying MWCNTs control of root hair morphogenesis.

Overexpression of alfalfa SIMK promotes root hair growth, nodule clustering and shoot biomass production.

SummaryNitrogen‐fixing rhizobia and legumes have developed complex mutualistic mechanism that allows to convert atmospheric nitrogen into ammonia. Signalling by mitogen‐activated protein kinases (MAPKs) seems to be involved in this symbiotic interaction. Previously, we reported that stress‐induced MAPK (SIMK) shows predominantly nuclear localization in alfalfa root epidermal cells. Nevertheless, SIMK is activated and relocalized to the tips of growing root hairs during their development. SIMK kinase (SIMKK) is a well‐known upstream activator of SIMK. Here, we characterized production parameters of transgenic alfalfa plants with genetically manipulated SIMK after infection with Sinorhizobium meliloti. SIMKK RNAi lines, causing strong downregulation of both SIMKK and SIMK, showed reduced root hair growth and lower capacity to form infection threads and nodules. In contrast, constitutive overexpression of GFP‐tagged SIMK promoted root hair growth as well as infection thread and nodule clustering. Moreover, SIMKK and SIMK downregulation led to decrease, while overexpression of GFP‐tagged SIMK led to increase of biomass in above‐ground part of plants. These data suggest that genetic manipulations causing downregulation or overexpression of SIMK affect root hair, nodule and shoot formation patterns in alfalfa, and point to the new biotechnological potential of this MAPK.

MiR-149-5p Regulates Goat Hair Follicle Stem Cell Proliferation and Apoptosis by Targeting the CMTM3/AR Axis During Superior-Quality Brush Hair Formation.

The Yangtze River Delta white goat is a unique goat species that can produce superior quality brush hair. CKLF-like MARVEL transmembrane domain-containing 3 (CMTM3), which influences the transcriptional activity of androgen receptor (AR), was identified as a candidate gene related to superior-quality brush hair formation. CMTM3 is generally expressed at low levels, but miR-149-5p is highly expressed in the skin tissues of these goats. The mechanism by which CMTM3 regulates the proliferation and apoptosis of goat hair follicle stem cells has not been elucidated. Here, RT-qPCR, western blotting, 5-ethynyl-2′-deoxyuridine (EdU), cell cycle, apoptosis, and dual-luciferase assays were used to investigate the role and regulatory mechanism of CMTM3 and miR-149-5p. Functional studies showed that CMTM3 overexpression inhibited proliferation and induced apoptosis in cultured hair follicle stem cells, whereas silencing CMTM3 markedly facilitated cell proliferation and deterred apoptosis in cultured hair follicle stem cells. Then, using bioinformatic predictions and the aforementioned assays, including dual-luciferase assays, RT-qPCR, and western blotting, we confirmed that miR-149-5p targets CMTM3 and preliminarily investigated the interaction between CMTM3 and AR in goat hair follicle stem cells. Furthermore, miR-149-5p overexpression significantly accelerated the proliferation and attenuated the apoptosis of hair follicle stem cells. Conversely, miR-149-5p inhibition suppressed the proliferation and induced the apoptosis of hair follicle stem cells. These results reveal a miR-149-5p-related regulatory framework for the miR-149-5p/CMTM3/AR axis during superior quality brush hair formation, in which CMTM3 plays a negative role.

A novel missense mutation within KRT75 gene strongly affects heat stress in Chinese cattle.

The KRT75 gene (Keratin 75) is a member of the type II epithelial α-keratin gene family which plays a key role in hair and nail formation. And the coat conformation affects heat tolarence in mammals. Therefore, the aim of this study was to identify novel single nucleotide polymorphisms (SNPs) of the KRT75 gene and further evaluate its relation to heat stress in Chinese cattle. A missense mutation (NC_037332.1: g.1052T>C) of the bovine KRT75 was identified using the Bovine Genome Variation Database (BGVD). The g.1052T>C variant was then genotyped in 519 individuals of 22 cattle breeds. Further analyses showed that the frequency of T allele in Chinese indigenous cattle breeds gradually diminished from northern groups to southern groups, whereas the frequency of C allele displayed a contrary patternl. Simultaneously, the frequency of the CC and CT genotype for southern groups was much greater than that of the TT genotype. Additionally, association analysis showed the genotypes were remarkably associated with mean annual temperature (T), relative humidity (RH) and temperature humidity index (THI) (P<0.01). Our results demonstrated that the KRT75 gene might be a candidate gene associated with the heat stress in Chinese cattle.

Boson and neutron stars with increased density

We discuss boson stars and neutron stars, respectively, in a scalar-tensor gravity model with an explicitly time-dependent real scalar field. While the boson stars in our model – in contrast to the neutron stars – do not possess a hard core, we find that the qualitative effects of the formation of scalar hair are similar in both cases: the presence of the gravity scalar allows both type of stars to exist for larger central density as well as larger mass at given radius than their General Relativity counterparts. In particular, we find new types of neutron stars with scalar hair which have radii very close to the corresponding Schwarzschild radius and hence are comparable in density to black holes. This new branch of solutions is stable with respect to the decay into individual baryons.

Rescuing key native traits in cultured dermal papilla cells for human hair regeneration

IntroductionThe dermal papilla (DP) represents the major regulatory entity within the hair follicle (HF), inducing hair formation and growth through reciprocal interactions with epithelial cells. However, human DP cells rapidly lose their hair inductive ability when cultured in an epithelium-deficient environment. ObjectivesTo determine if the conditioned medium collected from interfollicular keratinocytes (KCs-CM) is capable of improving DP cell native properties and inductive phenotype. MethodsDP cells were cultured with KCs-CM both in 2D and 3D culture conditions (spheroids). Further, the hair-inductive capacity of DP cells precultured with KCs-CM was tested in a hair reconstitution assay, after co-grafting with human keratinocytes in nude mice. ResultsWe demonstrate that KCs-CM contributes to restore the inductivity of cultured human DP cells in a more effective mode than the conventional 3D-cultures. This is supported by the higher active alkaline phosphatase (ALP) levels in DP cells, the improved self-aggregative capacity and the reduced expression of α-SMA and the V1-isoform of versican. Moreover, DP cells cultured with KCs-CM displayed a secretome profile (VEGF, BMP2, TGF- β1, IL-6) that matches the one observed during anagen. KCs-CM also enhanced DP cell proliferation, while preventing cells to undergo morphological changes characteristic of high passage cells. In opposition, the amount of collagenous and non-collagenous proteins deposited by DP cells was lower in the presence of KCs-CM. The improvement in ALP activity was maintained in 3D spheroidal cultures, even after KCs-CM retrieval, being superior to the effect of the gold-standard culture conditions. Moreover, DP cells cultured with KCs-CM and grafted with human keratinocytes supported the formation of HF- and sebaceous gland-like structures in mice. ConclusionThe proposed strategy encourages future cell-based strategies for HF regeneration not only in the context of hair-associated disorders, but also in the management of wounds to aid in restoring critical skin regulatory appendages.

Remodeling of Root Growth Under Combined Arsenic and Hypoxia Stress Is Linked to Nutrient Deprivation.

Root architecture responds to environmental stress. Stress-induced metabolic and nutritional changes affect the endogenous root development program. Transcriptional and translational changes realize the switch between stem cell proliferation and cell differentiation, lateral root or root hair formation and root functionality for stress acclimation. The current work explores the effects of stress combination of arsenic toxicity (As) and hypoxia (Hpx) on root development in Arabidopsis thaliana. As revealed previously, combined As and Hpx treatment leads to severe nutritional disorder evident from deregulation of root transcriptome and plant mineral contents. Both As and Hpx were identified to pose stress-specific constraints on root development that lead to unique root growth phenotype under their combination. Besides inhibition of root apical meristem (RAM) activity under all stresses, As induced lateral root growth while root hair density and lengths were strongly increased by Hpx and HpxAs-treatments.A dual stimulation of phosphate (Pi)-starvation response was observed for HpxAs-treated plant roots; however, the response under HpxAs aligned more with Hpx than As. Transcriptional evidence along with biochemical data suggests involvement of PHOSPHATE STARVATION RESPONSE 1; PHR1-dependent systemic signaling. Pi metabolism-related transcripts in close association with cellular iron homeostasis modulate root development under HpxAs. Early redox potential changes in meristematic cells, differential ROS accumulation in root hair zone cell layers and strong deregulation of NADPH oxidases, NADPH-dependent oxidoreductases and peroxidases signify a role of redox and ROS signaling in root architecture remodeling under HpxAs. Differential aquaporin expression suggests transmembrane ROS transport to regulate root hair induction and growth. Reorganization of energy metabolism through NO-dependent alternate oxidase, lactate fermentation, and phosphofructokinase seems crucial under HpxAs. TOR and SnRK-signaling network components were potentially involved in control of sustainable utilization of available energy reserves for root hair growth under combined stress as well as recovery on reaeration. Findings are discussed in context of combined stress-induced signaling in regulation of root development in contrast to As and Hpx alone.

Effect of Phloroglucinol on in Vitro Rooting of Sugarcane (Saccharum spp. cv C90-469)

The objective of this study was to determine the effect of phloroglucinol on in vitro rooting of sugarcane cultivar C90-469. A completely randomized experimental design was used with seven treatments, three concentrations of phloroglucinol (10, 15 and 20 mg L−1) in combination or not with 1.3 mg L−1 of indole-3-acetic acid (IAA) and as control the liquid culture medium without phloroglucinol. After 15 days of culture, the number of shoots rooted, height, number of leaves, fresh weight of the in vitro plant (gFW), number of roots, length of the main root and the total chlorophyll content (SPAD units) were evaluated. In the ex vitro acclimatization phase, the survival of the in vitro plants was evaluated 15 days after transplanting. Concentration of 20 mg L−1 of phloroglucinol combined with 1.3 mg L−1 of IAA and 40 g L−1 of sucrose had 100% rooting. A greater number of roots per plant, the formation of root hairs and a high survival percentage (87.8%) of the in vitro plants under ex vitro acclimatization conditions in a shade house were recorded.