66 research outputs found

    The Importance of Being on Time : Regulatory Networks Controlling Photoperiodic Flowering in Cereals

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    Flowering is the result of the coordination between genetic information and environmental cues. Gene regulatory networks have evolved in plants in order to measure diurnal and seasonal variation of day length (or photoperiod), thus aligning the reproductive phase with the most favorable season of the year. The capacity of plants to discriminate distinct photoperiods classifies them into long and short day species, depending on the conditions that induce flowering. Plants of tropical origin and adapted to short day lengths include rice, maize, and sorghum, whereas wheat and barley were originally domesticated in the Fertile Crescent and are considered long day species. In these and other crops, day length measurement mechanisms have been artificially modified during domestication and breeding to adapt plants to novel areas, to the extent that a wide diversity of responses exists within any given species. Notwithstanding the ample natural and artificial variation of day length responses, some of the basic molecular elements governing photoperiodic flowering are widely conserved. However, as our understanding of the underlying mechanisms improves, it becomes evident that specific regulators exist in many lineages that are not shared by others, while apparently conserved components can be recruited to novel functions during evolution

    Pharmacologic inhibition of JAK-STAT signaling promotes hair growth

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    Several forms of hair loss in humans are characterized by the inability of hair follicles to enter the growth phase (anagen) of the hair cycle after being arrested in the resting phase (telogen). Current pharmacologic therapies have been largely unsuccessful in targeting pathways that can be selectively modulated to induce entry into anagen. We show that topical treatment of mouse and human skin with small-molecule inhibitors of the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway results in rapid onset of anagen and subsequent hair growth. We show that JAK inhibition regulates the activation of key hair follicle populations such as the hair germ and improves the inductivity of cultured human dermal papilla cells by controlling a molecular signature enriched in intact, fully inductive dermal papillae. Our findings open new avenues for exploration of JAK-STAT inhibition for promotion of hair growth and highlight the role of this pathway in regulating the activation of hair follicle stem cells

    Molecular signatures define alopecia areata subtypes and transcriptional biomarkers

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    AbstractAlopecia areata (AA) is an autoimmune disease typified by nonscarring hair loss with a variable clinical course. In this study, we conducted whole genome gene expression analysis of 96 human scalp skin biopsy specimens from AA or normal control subjects. Based on gene expression profiling, samples formed distinct clusters based on the presence or absence of disease as well as disease phenotype (patchy disease compared with alopecia totalis or universalis). Differential gene expression analysis allowed us to robustly demonstrate graded immune activity in samples of increasing phenotypic severity and generate a quantitative gene expression scoring system that classified samples based on interferon and cytotoxic T lymphocyte immune signatures critical for disease pathogenesis

    Kappa Opioid receptor-induced aversion requires p38 MAPK activation in VTA dopamine neurons

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    The endogenous dynorphin-Îș opioid receptor (KOR) system encodes the dysphoric component of the stress response and controls the risk of depression-like and addiction behaviors; however, the molecular and neural circuit mechanisms are not understood. In this study, we report that KOR activation of p38α MAPK in ventral tegmental (VTA) dopaminergic neurons was required for conditioned place aversion (CPA) in mice. Conditional genetic deletion of floxed KOR or floxed p38α MAPK by Cre recombinase expression in dopaminergic neurons blocked place aversion to the KOR agonist U50,488. Selective viral rescue by wild-type KOR expression in dopaminergic neurons of KOR(−/−) mice restored U50,488-CPA, whereas expression of a mutated form of KOR that could not initiate p38α MAPK activation did not. Surprisingly, while p38α MAPK inactivation blocked U50,488-CPA, p38α MAPK was not required for KOR inhibition of evoked dopamine release measured by fast scan cyclic voltammetry in the nucleus accumbens. In contrast, KOR activation acutely inhibited VTA dopaminergic neuron firing, and repeated exposure attenuated the opioid response. This adaptation to repeated exposure was blocked by conditional deletion of p38α MAPK, which also blocked KOR-induced tyrosine phosphorylation of the inwardly rectifying potassium channel (GIRK) subunit Kir3.1 in VTA dopaminergic neurons. Consistent with the reduced response, GIRK phosphorylation at this amino terminal tyrosine residue (Y12) enhances channel deactivation. Thus, contrary to prevailing expectations, these results suggest that Îș opioid-induced aversion requires regulation of VTA dopaminergic neuron somatic excitability through a p38α MAPK effect on GIRK deactivation kinetics rather than by presynaptically inhibiting dopamine release. SIGNIFICANCE STATEMENT Kappa opioid receptor (KOR) agonists have the potential to be effective, nonaddictive analgesics, but their therapeutic utility is greatly limited by adverse effects on mood. Understanding how KOR activation produces dysphoria is key to the development of better analgesics and to defining how the endogenous dynorphin opioids produce their depression-like effects. Results in this study show that the aversive effects of Îș receptor activation required arrestin-dependent p38α MAPK activation in dopamine neurons but did not require inhibition of dopamine release in the nucleus accumbens. Thus, contrary to the prevailing view, inhibition of mesolimbic dopamine release does not mediate the aversive effects of KOR activation and functionally selective Îș opioids that do not activate arrestin signaling may be effective analgesics lacking dysphoric effects

    Antagonistic Transcription Factor Complexes Modulate the Floral Transition in Rice

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    Plants measure day or night lengths to coordinate specific developmental changes with a favorable season. In rice (Oryza sativa), the reproductive phase is initiated by exposure to short days when expression of HEADING DATE 3a (Hd3a) and RICE FLOWERING LOCUS T 1 (RFT1) is induced in leaves. The cognate proteins are components of the florigenic signal and move systemically through the phloem to reach the shoot apical meristem (SAM). In the SAM, they form a transcriptional activation complex with the bZIP transcription factor OsFD1 to start panicle development. Here, we show that Hd3a and RFT1 can form transcriptional activation or repression complexes also in leaves and feed back to regulate their own transcription. Activation complexes depend on OsFD1 to promote flowering. However, additional bZIPs, including Hd3a BINDING REPRESSOR FACTOR1 (HBF1) and HBF2, form repressor complexes that reduce Hd3a and RFT1 expression to delay flowering. We propose that Hd3a and RFT1 are also active locally in leaves to fine-tune photoperiodic flowering response

    Antibacterial Solution Using Cinnamomum verum (Cinammon) and Cympobogon citratus (Lemongrass) Essential Oils with Hydrogen Peroxide Against Staphylococcus aureus and Escherichia coli

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    Amidst the pandemic, millions of impoverished Filipinos lack sufficient access to sanitation services that protect them from bacterial infections. As such, this study endeavored to formulate a disinfectant spray of hydrogen peroxide and varying concentrations of lemongrass (Cymbopogon citratus) and cinnamon (Cinnamomum verum) essential oils to produce a maximally effective solution. Due to their natural origin, these essential oils were chosen for their extensive antibacterial properties, affordable price, and low toxicity levels. Six disinfectant spray solutions containing different concentrations of either essential oil were tested against Staphylococcus aureus and Escherichia coli bacteria through the agar disk diffusion method. After analyzing the data using mean, standard deviation, and MANOVA, it was found that including cinnamon and lemongrass essential oil had no statistically significant effect on the antibacterial activity of the hydrogen peroxide solution, regardless of the concentration of essential oil used, p \u3e 0.05. However, the lemongrass samples were slightly more effective than the cinnamon solutions. Thus, future researchers are encouraged to investigate other components that can potentially increase the antibacterial activity of a disinfectant spray

    Effects of Screening and Brief Intervention Training on Resident and Faculty Alcohol Intervention Behaviours: A Pre- Post-Intervention Assessment

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    Background: Many hazardous and harmful drinkers do not receive clinician advice to reduce their drinking. Previous studies suggest under-detection and clinician reluctance to intervene despite awareness of problem drinking (PD). The Healthy Habits Project previously reported chart review data documenting increased screening and intervention with hazardous and harmful drinkers after training clinicians and implementing routine screening. This report describes the impact of the Healthy Habits training program on clinicians\u27 rates of identification of PD, level of certainty in identifying PD and the proportion of patients given advice to reduce alcohol use, based on self-report data using clinician exit questionnaires. Methods: 28 residents and 10 faculty in a family medicine residency clinic completed four cycles of clinician exit interview questionnaires before and after screening and intervention training. Rates of identifying PD, level of diagnostic certainty, and frequency of advice to reduce drinking were compared across intervention status (pre vs. post). Findings were compared with rates of PD and advice to reduce drinking documented on chart review. Results: 1,052 clinician exit questionnaires were collected. There were no significant differences in rates of PD identified before and after intervention (9.8% vs. 7.4%, p = .308). Faculty demonstrated greater certainty in PD diagnoses than residents (p = .028) and gave more advice to reduce drinking (p = .042) throughout the program. Faculty and residents reported higher levels of diagnostic certainty after training (p = .039 and .030, respectively). After training, residents showed greater increases than faculty in the percentage of patients given advice to reduce drinking (p = .038), and patients felt to be problem drinkers were significantly more likely to receive advice to reduce drinking by all clinicians (50% vs. 75%, p = .047). The number of patients receiving advice to reduce drinking after program implementation exceeded the number of patients felt to be problem drinkers. Recognition rates of PD were four to eight times higher than rates documented on chart review (p = .028). Conclusion: This program resulted in greater clinician certainty in diagnosing PD and increases in the number of patients with PD who received advice to reduce drinking. Future programs should include booster training sessions and emphasize documentation of PD and brief intervention

    Envisioning more equitable and just futures: feminist organizational communication in theory and praxis

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    In this forum, we engage in a reflexive intergenerational conversation regarding the contributions of feminist scholars to organizational communication scholarship, as well as the potentials of feminist organizational communication theory and praxis to address urgent challenges facing our institutions and communities. We also offer critique of this body of work and grapple with its, and in some cases our own, shortcomings. In this article, we highlight four major themes from our conversations including (a) navigating between the center and the margins in feminist organizational communication, (b) making time for intersectionality, (c) reenvisioning academic work based on our feminist values, and (d) imagining feminist futures. We hope this forum will inspire others to join us in exploring innovative ways to advance feminist organizational communication theory, praxis, and pedagogy

    Overview : Integrative and Comprehensive Understanding on Polar Environments (iCUPE) - concept and initial results

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    The role of polar regions is increasing in terms of megatrends such as globalization, new transport routes, demography, and the use of natural resources with consequent effects on regional and transported pollutant concentrations. We set up the ERA-PLANET Strand 4 project "iCUPE - integrative and Comprehensive Understanding on Polar Environments" to provide novel insights and observational data on global grand challenges with an Arctic focus. We utilize an integrated approach combining in situ observations, satellite remote sensing Earth observations (EOs), and multi-scale modeling to synthesize data from comprehensive long-term measurements, intensive campaigns, and satellites to deliver data products, metrics, and indicators to stakeholders concerning the environmental status, availability, and extraction of natural resources in the polar areas. The iCUPE work consists of thematic state-of-the-art research and the provision of novel data in atmospheric pollution, local sources and transboundary transport, the characterization of arctic surfaces and their changes, an assessment of the concentrations and impacts of heavy metals and persistent organic pollutants and their cycling, the quantification of emissions from natural resource extraction, and the validation and optimization of satellite Earth observation (EO) data streams. In this paper we introduce the iCUPE project and summarize initial results arising out of the integration of comprehensive in situ observations, satellite remote sensing, and multi-scale modeling in the Arctic context.Peer reviewe
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