Ontogenetic development of the water channel protein AQP5 in mouse salivary gland tissue.

Aquaporins (AQP) are a family of channel proteins expressed in the cell membranes of many tissue types. As water channels, they enable the selective permeation of water molecules and thus play an important role in water transport through the plasma membrane. There are numerous AQP sub-types, among which AQP5 is expressed in the salivary glands. The expression and localization of AQP5 in different salivary gland cells of animal models during fetal development and after birth have enabled the physiological functions of AQP5 to be elucidated, but subsequent changes in the adult phase are unknown. It is known that saliva production tends to decrease with age, but it is unclear how AQP5 activity and function changes developmentally, from young to old including gender differences. In the present study, we sampled the parotid, submandibular, and sublingual glands from young (8 weeks old) and aged (12 months old) mice of both sexes to study the effects of age- and sex-related differences in AQP5 expression. Positive fluorescence immunostaining was detected in the membranes of cells from all gland types, and this was enhanced in juvenile mice from both sexes. Western blot analyses revealed that AQP5 expression levels tended to decrease with age in both male and female animals. Conversely, AQP5 gene expression levels did not change significantly with aging, but were found to be high in submandibular gland cells of both sexes, in parotid gland cells of older female mice, and in the sublingual gland cells of young male mice.

Biomarkers in the Rat Hippocampus and Peripheral Blood for an Early Stage of Mental Disorders Induced by Water Immersion Stress.

It is difficult to evaluate the pre-symptomatic state of mental disorders and prevent its onset. Since stress could be a trigger of mental disorders, it may be helpful to identify stress-responsive biomarkers (stress markers) for the evaluation of stress levels. We have so far performed omics analyses of the rat brain and peripheral blood after various kinds of stress and have found numerous factors that respond to stress. In this study, we investigated the effects of relatively moderate stress on these factors in the rat to identify stress marker candidates. Adult male Wistar rats underwent water immersion stress for 12 h, 24 h, or 48 h. Stress caused weight loss and elevated serum corticosterone levels, and alterations regarded as anxiety and/or fear-like behaviors. Reverse-transcription PCR and Western blot analyses revealed significant alterations in the expressions of hippocampal genes and proteins by the stress for no longer than 24 h, such as mitogen-activated protein kinase phosphatase 1 (MKP-1), CCAAT/enhancer-binding protein delta (CEBPD), small ubiquitin-like modifier proteins 1/sentrin-specific peptidase 5 (SENP5), matrix metalloproteinase-8 (MMP-8), kinase suppressor of Ras 1 (KSR1), and MKP-1, MMP-8, nerve growth factor receptor (NGFR). Similar alterations were observed in three genes (MKP-1, CEBPD, MMP-8) in the peripheral blood. The present results strongly suggest that these factors may serve as stress markers. The correlation of these factors in the blood and brain may enable the evaluation of stress-induced changes in the brain by blood analysis, which will contribute to preventing the onset of mental disorders.

Molecular and Physiological Functions of PACAP in Sweat Secretion.

Sweat plays a critical role in human body, including thermoregulation and the maintenance of the skin environment and health. Hyperhidrosis and anhidrosis are caused by abnormalities in sweat secretion, resulting in severe skin conditions (pruritus and erythema). Bioactive peptide and pituitary adenylate cyclase-activating polypeptide (PACAP) was isolated and identified to activate adenylate cyclase in pituitary cells. Recently, it was reported that PACAP increases sweat secretion via PAC1R in mice and promotes the translocation of AQP5 to the cell membrane through increasing intracellular [Ca2+] via PAC1R in NCL-SG3 cells. However, intracellular signaling mechanisms by PACAP are poorly clarified. Here, we used PAC1R knockout (KO) mice and wild-type (WT) mice to observe changes in AQP5 localization and gene expression in sweat glands by PACAP treatment. Immunohistochemistry revealed that PACAP promoted the translocation of AQP5 to the lumen side in the eccrine gland via PAC1R. Furthermore, PACAP up-regulated the expression of genes (Ptgs2, Kcnn2, Cacna1s) involved in sweat secretion in WT mice. Moreover, PACAP treatment was found to down-regulate the Chrna1 gene expression in PAC1R KO mice. These genes were found to be involved in multiple pathways related to sweating. Our data provide a solid basis for future research initiatives in order to develop new therapies to treat sweating disorders.

OMICS Analyses Unraveling Related Gene and Protein-Driven Molecular Mechanisms Underlying PACAP 38-Induced Neurite Outgrowth in PC12 Cells.

The study aimed to understand mechanism/s of neuronal outgrowth in the rat adrenal-derived pheochromocytoma cell line (PC12) under pituitary adenylate cyclase-activating polypeptide (PACAP) treatment. Neurite projection elongation was suggested to be mediated via Pac1 receptor-mediated dephosphorylation of CRMP2, where GSK-3ß, CDK5, and Rho/ROCK dephosphorylated CRMP2 within 3 h after addition of PACAP, but the dephosphorylation of CRMP2 by PACAP remained unclear. Thus, we attempted to identify the early factors in PACAP-induced neurite projection elongation via omics-based transcriptomic (whole genome DNA microarray) and proteomic (TMT-labeled liquid chromatography-tandem mass spectrometry) analyses of gene and protein expression profiles from 5-120 min after PACAP addition. The results revealed a number of key regulators involved in neurite outgrowth, including known ones, called 'Initial Early Factors', e.g., genes Inhba, Fst, Nr4a1,2,3, FAT4, Axin2, and proteins Mis12, Cdk13, Bcl91, CDC42, including categories of 'serotonergic synapse, neuropeptide and neurogenesis, and axon guidance'. cAMP signaling and PI3K-Akt signaling pathways and a calcium signaling pathway might be involved in CRMP2 dephosphorylation. Cross-referencing previous research, we tried to map these molecular components onto potential pathways, and we may provide important new information on molecular mechanisms of neuronal differentiation induced by PACAP. Gene and protein expression data are publicly available at NCBI GSE223333 and ProteomeXchange, identifier PXD039992.

Transcriptomic (DNA Microarray) and Metabolome (LC-TOF-MS) Analyses of the Liver in High-Fat Diet Mice after Intranasal Administration of GALP (Galanin-like Peptide).

The aim of this research was to test the efficacy and potential clinical application of intranasal administration of galanin-like peptide (GALP) as an anti-obesity treatment under the hypothesis that GALP prevents obesity in mice fed a high-fat diet (HFD). Focusing on the mechanism of regulation of lipid metabolism in peripheral tissues via the autonomic nervous system, we confirmed that, compared with a control (saline), intranasally administered GALP prevented further body weight gain in diet-induced obesity (DIO) mice with continued access to an HFD. Using an omics-based approach, we identified several genes and metabolites in the liver tissue of DIO mice that were altered by the administration of intranasal GALP. We used whole-genome DNA microarray and metabolomics analyses to determine the anti-obesity effects of intranasal GALP in DIO mice fed an HFD. Transcriptomic profiling revealed the upregulation of flavin-containing dimethylaniline monooxygenase 3 (Fmo3), metallothionein 1 and 2 (Mt1 and Mt2, respectively), and the Aldh1a3, Defa3, and Defa20 genes. Analysis using the DAVID tool showed that intranasal GALP enhanced gene expression related to fatty acid elongation and unsaturated fatty acid synthesis and downregulated gene expression related to lipid and cholesterol synthesis, fat absorption, bile uptake, and excretion. Metabolite analysis revealed increased levels of coenzyme Q10 and oleoylethanolamide in the liver tissue, increased levels of deoxycholic acid (DCA) and taurocholic acid (TCA) in the bile acids, increased levels of taurochenodeoxycholic acid (TCDCA), and decreased levels of ursodeoxycholic acid (UDCA). In conclusion, intranasal GALP administration alleviated weight gain in obese mice fed an HFD via mechanisms involving antioxidant, anti-inflammatory, and fatty acid metabolism effects and genetic alterations. The gene expression data are publicly available at NCBI GSE243376.

Examining the Effect of Notocactus ottonis Cold Vacuum Isolated Plant Cell Extract on Hair Growth in C57BL/6 Mice Using a Combination of Physiological and OMICS Analyses.

The biological and psychological importance of hair is recognized worldwide. Molecules that can promote the activation of hair follicle stem cells and the initiation of the growth phase have been subjects of research. Clarifying how hair regeneration is regulated may help to provide hair loss treatments, including cosmetic and even psychological interventions. We examined the hair-growing effects of a cell extract (CE) obtained from cactus Notocactus ottonis by the cold vacuum extraction protocol, by investigating its hair-growing effects, relevant mechanisms, and potential factors therein. Using male C57BL/6 mice, vehicle control (VC: propylene glycol: ethanol: water), MXD (minoxidil, positive control), and N. ottonis CE (N-CE, experimental) were applied topically to the backs of mice. The results showed that MXD and N-CE were more effective in promoting hair growth than VC. An increase in number of hair follicles was observed with N-CE in hematoxylin-eosin-stained skin tissue. The metabolite composition of N-CE revealed the presence of growth-promoting factors. Using mouse back whole-skin tissue samples, whole-genome DNA microarray (4 × 44 K, Agilent) and proteomics (TMT-based liquid chromatography-tandem mass spectrometry) analyses were carried out, suggesting the molecular factors underlying hair-promoting effects of N-CE. This study raises the possibility of using the newly described N. ottonis CE as a hair-growth-promoting agent.

Leptin in hippocampus mediates benefits of mild exercise by an antioxidant on neurogenesis and memory.

Regular exercise and dietary supplements with antioxidants each have the potential to improve cognitive function and attenuate cognitive decline, and, in some cases, they enhance each other. Our current results reveal that low-intensity exercise (mild exercise, ME) and the natural antioxidant carotenoid astaxanthin (AX) each have equivalent beneficial effects on hippocampal neurogenesis and memory function. We found that the enhancement by ME combined with AX in potentiating hippocampus-based plasticity and cognition is mediated by leptin (LEP) made and acting in the hippocampus. In assessing the combined effects upon wild-type (WT) mice undergoing ME with or without an AX diet for four weeks, we found that, when administrated alone, ME and AX separately enhanced neurogenesis and spatial memory, and when combined they were at least additive in their effects. DNA microarray and bioinformatics analyses revealed not only the up-regulation of an antioxidant gene, ABHD3, but also that the up-regulation of LEP gene expression in the hippocampus of WT mice with ME alone is further enhanced by AX. Together, they also increased hippocampal LEP (h-LEP) protein levels and enhanced spatial memory mediated through AKT/STAT3 signaling. AX treatment also has direct action on human neuroblastoma cell lines to increase cell viability associated with increased LEP expression. In LEP-deficient mice (ob/ob), chronic infusion of LEP into the lateral ventricles restored the synergy. Collectively, our findings suggest that not only h-LEP but also exogenous LEP mediates effects of ME on neural functions underlying memory, which is further enhanced by the antioxidant AX.

Potential Therapeutic Role of Pituitary Adenylate Cyclase-Activating Polypeptide for Dry Eye Disease.

Dry eye disease (DED) is caused by a reduction in the volume or quality of tears. The prevalence of DED is estimated to be 100 million in the developed world. As aging is a risk factor for DED, the prevalence of DED is expected to grow at a rapid pace in aging populations, thus creating an increased need for new therapies. This review summarizes DED medications currently in clinical use. Most current medications for DED focus on stimulating tear secretion, mucin secretion, or suppressing inflammation, rather than simply replenishing the ocular surface with moisture to improve symptoms. We recently reported that the neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide) induces tear secretion and suppresses corneal injury caused by a reduction in tears. Moreover, it has been reported that a PACAP in water and a 0.9% saline solution at +4 °C showed high stability and achieved 80-90% effectiveness after 2 weeks of treatment. These results reveal PACAP as a candidate DED medication. Further research on the clinical applications of PACAP in DED is necessary.

Unravelling the Helianthus tuberosus L. (Jerusalem Artichoke, Kiku-Imo) Tuber Proteome by Label-Free Quantitative Proteomics.

The present research investigates the tuber proteome of the 'medicinal' plant Jerusalem artichoke (abbreviated as JA) (Helianthus tuberosus L.) using a high-throughput proteomics technique. Although JA has been historically known to the Native Americans, it was introduced to Europe in the late 19th century and later spread to Japan (referred to as 'kiku-imo') as a folk remedy for diabetes. Genboku Takahashi research group has been working on the cultivation and utilization of kiku-imo tuber as a traditional/alternative medicine in daily life and researched on the lowering of blood sugar level, HbA1c, etc., in human subjects (unpublished data). Understanding the protein components of the tuber may shed light on its healing properties, especially related to diabetes. Using three commercially processed JA tuber products (dried powder and dried chips) we performed total protein extraction on the powdered samples using a label-free quantitate proteomic approach (mass spectrometry) and catalogued for the first time a comprehensive protein list for the JA tuber. A total of 2967 protein groups were identified, statistically analyzed, and further categorized into different protein classes using bioinformatics techniques. We discussed the association of these proteins to health and disease regulatory metabolism. Data are available via ProteomeXchange with identifier PXD030744.

Molecular Mechanism for PACAP 38-Induced Neurite Outgrowth in PC12 Cells.

The present research investigates the molecular mechanism of neurite outgrowth (protrusion elongation) under pituitary adenylate cyclase-activating polypeptide (PACAP) 38 treatments using a rat adrenal-derived pheochromocytoma cell line-PC12. This study specifically looks into the regulation of PACAP38-induced collapsing response mediator protein 2 (CRMP2) previously identified in a mouse brain ischemia model and which could be recovered by PACAP38 treatment. Previously, DNA microarray analysis revealed that PACAP 38-mediated neuroprotection involved not only CRMP2 but also pathways related to glycogen synthase kinase-3ß (GSK-3ß) and other signaling components. Thus, to clarify whether CRMP2 acts directly on PACAP38 or through GSK-3ß as part of the mechanism of PACAP38-induced neurite outgrowth, we observed neurite outgrowth in the presence of GSK-3ß inhibitors and activators. PC12 cells were treated with PACAP38 being added to the cell culture medium at concentrations of 10-7 M, 10-8 M, and 10-9 M. Post PACAP38 treatment, immunostaining was used to confirm protrusion elongation of the PC12 cells, while RT-PCR, two-dimensional gel electrophoresis in conjunction with Western blotting, and inhibition experiments were performed to confirm the expression of the PACAP gene, its receptors, and downstream signaling components. Our data show that neurite protrusion elongation by PACAP38 (10-7 M) in PC12 cells is mediated through the PAC1-R receptor as demonstrated by its suppression by a specific inhibitor PA-8. Inhibitor experiments suggested that PACAP38-triggered neurite protrusion follows a GSK-3ß-regulated pathway, where the AKT and cAMP/ERK pathways are involved and where the inhibition of Rho/Roc could enhance neurite protrusion under PACAP38 stimulation. Although we could not yet confirm the exact role and position of CRMP2 in PACAP38-mediated PC12 cell elongation, it appears that its phosphorylation and dephosphorylation have a correlation with the neurite protrusion elongation through the interplay of CDK5, which needs to be investigated further.

Progress Toward Rice Seed OMICS in Low-Level Gamma Radiation Environment in Iitate Village, Fukushima.

Here, we present an update on the next level of experiments studying the impact of the gamma radiation environment, created post-March, 2011 nuclear accident at Fukushima Daiichi nuclear power plant, on rice plant and its next generation-the seed. Japonica-type rice (Oryza sativa L. cv. Koshihikari) plant was exposed to low-level gamma radiation (~4 µSv/h) in the contaminated Iitate Farm field in Iitate village (Fukushima). Seeds were harvested from these plants at maturity, and serve as the treated group. For control group, seeds (cv. Koshihikari) were harvested from rice grown in clean soil in Soma city, adjacent to Iitate village, in Fukushima. Focusing on the multi-omics approach, we have investigated the dry mature rice seed transcriptome, proteome, and metabolome following cultivation of rice in the radionuclide contaminated soil and compared it with the control group seed (non-radioactive field-soil environment). This update article presents an overview of both the multi-omics approach/technologies and the first findings on how rice seed has changed or adapted its biology to the low-level radioactive environment.

Retroviral induction of GSK-3ß expression blocks the stimulatory action of physical exercise on the maturation of newborn neurons.

Adult hippocampal neurogenesis (AHN) is a key process for certain types of hippocampal-dependent learning. Alzheimer's disease (AD) is accompanied by memory deficits related to alterations in AHN. Given that the increased activity of GSK-3ß has been related to alterations in the population of hippocampal granule neurons in AD patients, we designed a novel methodology by which to induce selective GSK-3ß overexpression exclusively in newborn granule neurons. To this end, we injected an rtTA-IRES-EGFP-expressing retrovirus into the hippocampus of tTO-GSK-3ß mice. Using this novel retroviral strategy, we found that GSK-3ß caused a cell-autonomous impairment of the morphological and synaptic maturation of newborn neurons. In addition, we examined whether GSK-3ß overexpression in newborn neurons limits the effects of physical activity. While physical exercise increased the number of dendritic spines, the percentage of mushroom spines, and the head diameter of the same in tet-OFF cells, these effects were not triggered in tet-ON cells. This observation suggests that GSK-3ß blocks the stimulatory actions of exercise. Given that the activity of GSK-3ß is increased in the brains of individuals with AD, these data may be relevant for non-pharmacological therapies for AD.

Unraveling the seed endosperm proteome of the lotus (Nelumbo nucifera Gaertn.) utilizing 1DE and 2DE separation in conjunction with tandem mass spectrometry.

Nelumbo nucifera (Gaertn.) or lotus, is an aquatic plant native to India, and presently consumed as food mainly in China and Japan. Lotus is also widely used in Indian and Chinese traditional medicine. Extracts from different parts of the lotus plant have been reported to show diverse biological activities-antioxidant, free radical scavenging, anti-inflammatory, and immunomodulatory. Despite this, little work has been done in isolating and identifying proteins responsible for these activities, or yet importantly to establish a lotus proteome. The aim of our group is to develop a proteome catalog of the lotus plant, starting with its seed, the nutrient rich food source. In this present study, the seed endosperm-most abundant in proteins, and main nutrient storage tissue-was targeted for protein extraction by testing five different extraction protocols, followed by their proteomic analyses using complementary 1DE and 2DE approaches in conjunction with MS/MS. The inventory of 66 nonredundant proteins obtained by 1DE-MS and the 30 obtained by 2DE-MS provides the first catalog of the lotus seed endosperm, where the most abundant protein functions were in categories of metabolic activities related to carbohydrate metabolism and nutrient storage.

Identification of cis- and trans-acting factors involved in the localization of MALAT-1 noncoding RNA to nuclear speckles.

MALAT-1 noncoding RNA is localized to nuclear speckles despite its mRNA-like characteristics. Here, we report the identification of several key factors that promote the localization of MALAT-1 to nuclear speckles and also provide evidence that MALAT-1 is involved in the regulation of gene expression. Heterokaryon assays revealed that MALAT-1 does not shuttle between the nucleus and cytoplasm. RNAi-mediated repression of the nuclear speckle proteins, RNPS1, SRm160, or IBP160, which are well-known mRNA processing factors, resulted in the diffusion of MALAT-1 to the nucleoplasm. We demonstrated that MALAT-1 contains two distinct elements directing transcripts to nuclear speckles, which were also capable of binding to RNPS1 in vitro. Depletion of MALAT-1 represses the expression of several genes. Taken together, our results suggest that RNPS1, SRm160, and IBP160 contribute to the localization of MALAT-1 to nuclear speckles, where MALAT-1 could be involved in regulating gene expression.

Unraveling low-level gamma radiation--responsive changes in expression of early and late genes in leaves of rice seedlings at Iitate Village, Fukushima.

In the summer of 2012, 1 year after the nuclear accident in March 2011 at the Fukushima Daiichi nuclear power plant, we examined the effects of gamma radiation on rice at a highly contaminated field of Iitate village in Fukushima, Japan. We investigated the morphological and molecular changes on healthy rice seedlings exposed to continuous low-dose gamma radiation up to 4 µSv h(-1), about 80 times higher than natural background level. After exposure to gamma rays, expression profiles of selected genes involved in DNA replication/repair, oxidative stress, photosynthesis, and defense/stress functions were examined by RT-PCR, which revealed their differential expression in leaves in a time-dependent manner over 3 days (6, 12, 24, 48, and 72 h). For example, OsPCNA mRNA rapidly increased at 6, 12, and 24 h, suggesting that rice cells responded to radiation stress by activating a gene involved in DNA repair mechanisms. At 72 h, genes related to the phenylpropanoid pathway (OsPAL2) and cell death (OsPR1oa) were strongly induced, indicating activation of defense/stress responses. We next profiled the transcriptome using a customized rice whole-genome 4×44K DNA microarray at early (6h) and late (72 h) time periods. Low-level gamma radiation differentially regulated rice leaf gene expression (induced 4481 and suppressed 3740 at 6 h and induced 2291 and suppressed 1474 genes at 72 h) by at least 2-fold. Using the highly upregulated and downregulated gene list, MapMan bioinformatics tool generated diagrams of early and late pathways operating in cells responding to gamma ray exposure. An inventory of a large number of gamma radiation-responsive genes provides new information on novel regulatory processes in rice.

Comprehensive analysis of neonatal versus adult unilateral decortication in a mouse model using behavioral, neuroanatomical, and DNA microarray approaches.

Previously, studying the development, especially of corticospinal neurons, it was concluded that the main compensatory mechanism after unilateral brain injury in rat at the neonatal stage was due in part to non-lesioned ipsilateral corticospinal neurons that escaped selection by axonal elimination or neuronal apoptosis. However, previous results suggesting compensatory mechanism in neonate brain were not correlated with high functional recovery. Therefore, what is the difference among neonate and adult in the context of functional recovery and potential mechanism(s) therein? Here, we utilized a brain unilateral decortication mouse model and compared motor functional recovery mechanism post-neonatal brain hemisuction (NBH) with adult brain hemisuction (ABH). Three analyses were performed: (1) Quantitative behavioral analysis of forelimb movements using ladder walking test; (2) neuroanatomical retrograde tracing analysis of unlesioned side corticospinal neurons; and (3) differential global gene expressions profiling in unlesioned-side neocortex (rostral from bregma) in NBH and ABH on a 8 × 60 K mouse whole genome Agilent DNA chip. Behavioral data confirmed higher recovery ability in NBH over ABH is related to non-lesional frontal neocortex including rostral caudal forelimb area. A first inventory of differentially expressed genes genome-wide in the NBH and ABH mouse model is provided as a resource for the scientific community.

PACAP38 differentially effects genes and CRMP2 protein expression in ischemic core and penumbra regions of permanent middle cerebral artery occlusion model mice brain.

Pituitary adenylate-cyclase activating polypeptide (PACAP) has neuroprotective and axonal guidance functions, but the mechanisms behind such actions remain unclear. Previously we examined effects of PACAP (PACAP38, 1 pmol) injection intracerebroventrically in a mouse model of permanent middle cerebral artery occlusion (PMCAO) along with control saline (0.9% NaCl) injection. Transcriptomic and proteomic approaches using ischemic (ipsilateral) brain hemisphere revealed differentially regulated genes and proteins by PACAP38 at 6 and 24 h post-treatment. However, as the ischemic hemisphere consisted of infarct core, penumbra, and non-ischemic regions, specificity of expression and localization of these identified molecular factors remained incomplete. This led us to devise a new experimental strategy wherein, ischemic core and penumbra were carefully sampled and compared to the corresponding contralateral (healthy) core and penumbra regions at 6 and 24 h post PACAP38 or saline injections. Both reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to examine targeted gene expressions and the collapsin response mediator protein 2 (CRMP2) protein profiles, respectively. Clear differences in expression of genes and CRMP2 protein abundance and degradation product/short isoform was observed between ischemic core and penumbra and also compared to the contralateral healthy tissues after PACAP38 or saline treatment. Results indicate the importance of region-specific analyses to further identify, localize and functionally analyse target molecular factors for clarifying the neuroprotective function of PACAP38.

DNA Microarray and Bioinformatic Analysis Reveals the Potential of Whale Oil in Enhancing Hair Growth in a C57BL/6 Mice Dorsal Skin Model.

Much research has been conducted to determine how hair regeneration is regulated, as this could provide therapeutic, cosmetic, and even psychological interventions for hair loss. The current study focused on the hair growth effect and effective utilization of fatty oil obtained from Bryde's whales through a high-throughput DNA microarray approach in conjunction with immunohistochemical observations. The research also examined the mechanisms and factors involved in hair growth. In an experiment using female C57BL/6J mice, the vehicle control group (VC: propylene glycol: ethanol: water), the positive control group (MXD: 3% minoxidil), and the experimental group (WO: 20% whale oil) were topically applied to the dorsal skin of the mouse. The results showed that 3% MXD and 20% WO were more effective than VC in promoting hair growth, especially 20% WO. Furthermore, in hematoxylin and eosin-stained dorsal skin tissue, an increase in the number of hair follicles and subcutaneous tissue thickness was observed with 20% WO. Whole-genome transcriptome analysis also confirmed increases for 20% WO in filaggrin (Flg), a gene related to skin barrier function; fibroblast growth factor 21 (Fgf21), which is involved in hair follicle development; and cysteine-rich secretory protein 1 (Crisp1), a candidate gene for alopecia areata. Furthermore, the results of KEGG pathway analysis indicated that 20% WO may have lower stress and inflammatory responses than 3% MXD. Therefore, WO is expected to be a safe hair growth agent.

Genome-wide mapping of the ozone-responsive transcriptomes in rice panicle and seed tissues reveals novel insight into their regulatory events.

The 'ozone (O3)-responsive transcriptome' behavior in the panicles and grains of rice plant was studied individually through high-throughput oligo-DNA microarray technique. O3 differentially and separately regulated 620 and 130 genes in the panicles and grains. Among the O3-responsive genes, 176 and 444 genes were up- and down-regulated in panicle compared to 24 and 106 genes in grain, respectively. Further mapping revealed that the majority of differentially expressed genes were mainly involved in signaling, hormonal, cell wall, transcription, proteolysis, and defense events. Many previously unknown O3-responsive novel genes were identified. Inventory of 745 O3-responsive genes and their mapping will expand our knowledge on novel regulatory processes in both panicles and grains of rice; and, serve as a resource towards the designing of rice crops for future high-O3world. PURPOSE OF WORK: Tropospheric ozone (O3) severely affects agricultural production worldwide. Present study aims to reveal a detailed O3 responsive gene network in panicle and grains of rice plants through transcriptomics approach. Our results provide an insight into the basis of O3-response in rice plants, and will help to develop suitable rice genotype for future high O3- world.

Galanin receptors modulate cutaneous vasodilation elicited by whole-body and local heating but not thermal sweating in young adults.

Galanin receptor subtypes GAL1, GAL2, and GAL3 are involved in several biological functions. We hypothesized that 1) GAL3 receptor activation contributes to sweating but limits cutaneous vasodilation induced by whole-body and local heating without a contribution of GAL2; and 2) GAL1 receptor activation attenuates both sweating and cutaneous vasodilation during whole-body heating. Young adults underwent whole-body (n = 12, 6 females) and local (n = 10, 4 females) heating. Forearm sweat rate (ventilated capsule) and cutaneous vascular conductance (CVC; ratio of laser-Doppler blood flow to mean arterial pressure) were assessed during whole-body heating (water-perfusion suit circulated with warm (35 °C) water), while CVC was also assessed by local forearm heating (from 33 °C to 39 °C and elevated to 42 °C thereafter; each level of heating maintained for ∼30 min). Sweat rate and CVC were evaluated at four intradermal microdialysis forearm sites treated with either 1) 5% dimethyl sulfoxide (control), 2) M40, a non-selective GAL1 and GAL2 receptor antagonist, 3) M871 to selectively antagonize GAL2 receptor, or 4) SNAP398299 to selectively antagonize GAL3 receptor. Sweating was not modulated by any GAL receptor antagonist (P > 0.169), whereas only M40 reduced CVC (P ≤ 0.003) relative to control during whole-body heating. Relative to control, SNAP398299 augmented the initial and sustained increase in CVC during local heating to 39 °C, and the transient increase at 42 °C (P ≤ 0.028). We confirmed that while none of the galanin receptors modulate sweating during whole-body heating, GAL1 receptors mediate cutaneous vasodilation. Further, GAL3 receptors blunt cutaneous vasodilation during local heating.