A new species of Urocleidoides Mizelle & Price 1964 (Monogenea: Dactylogyridae) parasite of Hemiodus orthonops Eigenmann & Kennedy, 1903 (Hemiodontidae) from the upper Paraná River floodplain.

During the study of ectoparasites (Platyhelminthes) of fish in the floodplain of the Upper Paraná River - Brazil, a new species of Urocleidoides, present in the gill filaments of Hemiodus orthonops (Hemiodontidae), is described using morphological description and molecular data from the mitochondrial region of cytochrome c oxidase, subunit 1 (COI) and the partial region of the 28S rDNA gene. Urocleidoides luquei n. sp. differs from all its congeners by the presence of a filament that joins the accessory piece to the base of the male copulatory organ and resembles U. paradoxus and U. surianoae. Phylogenetic analyses using molecular data revealed that U. luquei n. sp. forms a paraphyletic group concerning the other Urocleidoides species. In this way, as well as contributing to the description of a new species, we seek to encourage and contribute to the increase in research using integrative taxonomy, thus making it possible to elucidate some unresolved questions about the genus Urocleidoides.

[Survey by SFRO, SNRO and AFPPE about the evolution of the radiation therapist profession in France]. / Enquête SFRO­SNRO­AFPPE sur l'évolution du métier de manipulateur exerçant en radiothérapie en France.

PURPOSE: As part of the multidisciplinary team, radiation therapists are in charge of elements of treatment preparation and delivery of radiotherapy to cancer patients. Helping scientific and technological improvements, more and more patients with cancer were treated with radiotherapy including hypofractionnated radiotherapy, that explain the increase of demands on services. The professional impacted by this increase of demands are radiation oncologists and medical physicists. The opportunity to push forward the radiation therapist's competencies appears with the possibility to shift them some tasks. In this context, a first work was performed with objectives to have an overview of the tasks shifted to radiation therapists in France, the tasks that they could perform but also to evaluate some criteria of job satisfaction. MATERIAL AND METHODS: The committee of "new status and value of status" including six radiation oncologists (the French society of radiation oncology [SFRO] et national union of radiation oncologists [SNRO]) and six radiation therapists committee members of the French association of radiation therapists (AFPPE), built a questionnaire including three parts: demographic characteristics, tasks shifted and job satisfaction criteria. In total, the questionnaire included 19 questions and 24 items assessed with a four point-Likert scale (ranging from "completely disagree" to "completely agree"). This survey, formatting with google form, was tested by the committee members and the final version was sent to the SFRO, AFPPE and SNRO members, before being disseminated on the social networks. RESULTS: From November 18th 2022 to December 31st 2022, 492 responses were received (response rate=18.3%): 55 % of the respondents had at least 11 years of experience in radiotherapy. The respondents worked in different type of health facilities (36 % in specialized cancer centres, 19.5 % in private centers, 17.5% in university and general hospital, 10.2% in general hospital). More than » of the respondents had a teaching lecturer activity, 20% had a management team activity and a research activity for 18%. Less than 10% of the respondents had another degree than that of radiation therapist: university degree (n=27), degree in dosimetry (n=11) and master (n=3). More than 76% would like to be trained and to have access to the advanced practice, more than 50% would like expend competencies with a university degree, 30% with a master and 67% would like to participate in research. Forty-two percent of the respondents were involved in a task shifting (excluding decree relating to acts and activities carried out by radiation therapists) and among the radiation therapists non-involved, 63% would be interested in being. Regarding job satisfaction, 53% of the respondents were satisfied with their job and their salary and 68% believed that their job occupation is in line with their professional aspirations. More than 2/3 of the respondents described a significant workload and mental load, 53% thought to have time for their patient care and 70% felt some organisational difficulties. CONCLUSION: This survey shows: (i) A significant involvement of radiation therapists in the task shifting; (ii) A very strong demand for career development, in particular with existing degrees or to be created degree such as advanced practice; and (iii) The need to reinforce a job satisfaction for almost the half of the respondents, linked to a workload, a mental load and some organisational difficulties.

[Radiation therapists shortage in France: Organizational consequences and difficulties in deploying new missions and/or tasks delegation]. / Métier de manipulateur en radiothérapie en tension en France : conséquences organisationnelles et difficultés à déployer de nouvelles missions et/ou délégation de tâches.

PURPOSE: Radiation therapists shortage has been evaluated at national level in France, specifically in oncology radiotherapy, in terms of: (i) organizational adaptations, (ii) impact on patients care, and (iii) difficulties in deploying new missions and/or tasks delegation. MATERIALS AND METHODS: French professional organisations representing radiation therapists - SFRO, SNRO and AFPPE - sent their members a national survey (ten questions on 32 items). RESULTS: From 18 November 2022 to 31 December 2022, 55 responses were received (response rate: 31%) from radiotherapy managers or department heads; 51% had a structure comprising three to five treatment rooms (receiving 500 to 1000 patients per year [36%], or 1500 to 2000 patients per year [33%]). Activities performed were intensity-modulated radiotherapy (100%), stereotaxic radiotherapy (85%), brachytherapy (40%), adaptive radiotherapy (34%). These structures described consequences in closing machine time for 25% of them (reduction of the hourly volume greater than 10% in 57%) with the following consequences in the last 6 months: (i) an extension of the period of medical care (78%), a closing of one or more accelerators (50%) and the development of moderate hypofractionation scheme or extreme hypofractionation (50%). In current functioning, linear accelerators can deliver treatments with a team of two radiation therapists per room for a short day (43%) or two to four radiation therapists per room teams for a long day (40%). During the last 6 months, there has been a 10% increase in linear accelerators operating with a single team. (ii) regarding treatment planning: 16.4% reported a decrease in the opening amplitude (less than 20% in 44% of cases, from 20 to 50% in 33 % of cases). The initial scheduling of appointments for radiotherapy sessions was carried out by radiation therapists in 84% of the departments in current functioning (0.1 to 1 FTE dedicated to this activity in 62% of the departments). Over the last 6 months, there has been a clear reduction in the number of dedicated FTEs: [FTE=0.1 to 1]=-8%; [FTE=0]=+7%. (ii) Regarding tasks delegation (excluding the decree on acts and activities carried out by the radiation therapist): organ at risk delineation is partially performed by radiation therapist in 26% of the centres; caregiver support time in 78% (56% totally or 22% partially). This activity has been reduced by 42%. Seventy-five percent of departments want to develop new techniques, patient-centered approaches (44%), implement task delegation (organ at risk delineation: 58%; weekly consultations: 67%; positioning imaging validation: 71%), and 78% of departments are interested in developing advanced radiotherapy practice. However, the number of radiation therapists is considered insufficient in their implementation in 76% of cases (one to two FTE missing for 72% of structures). CONCLUSION: This survey shows a significant impact of radiation therapist shortage in radiotherapy oncology care (treatment delays, access to caregiver support time, workload on treatment teams), and represents a major obstacle to the development of radiotherapy structures.

[The first steps towards advanced practice for radiation therapists]. / Les prémices de la pratique avancée pour le manipulateur en radiothérapie.

The implementation of advanced practice in RT requires evidence regarding the clinical practices of radiation therapists (RTT) in the field. In this context, the goal of this article is to report the roles assigned to RTT in order to meet the demands of patients, RT services, and/or healthcare professionals. As part of the French Society of Oncologic Radiotherapy's congress, the Radiotherapy Committee of the French Association of radiographers presented a scientific program encompassing three main themes: patient follow-up by a RTT, the expertise of an RTT in Image Guided Radiation Therapy (IGRT), Adaptive Radiotherapy (ART), and the involvement of a RTT in research. This article presents an overview of five oral presentations that highlight concrete examples of roles assigned to RTTs in these specific domains. The follow-up of patients has been assigned to RTT. Research and development have been recognized as activities in which RTT play a significant role. The establishment of RTT specializing in IGRT has been reported to facilitate decision-making and is essential in ensuring professional expertise. Lastly, there is a need to enhance RTT skills in adaptive RT to support the implementation of this technique. These roles described as advanced practice meet needs and require a specific organisational framework and appropriate education and training (master type). Activities such as post-RT follow-up, validation of positioning imaging, delineation, writing research protocols, and involvement in the development of technological innovations were identified as essential tasks that can be assigned to RTT.

Limited vertical tarsal resection in a case of basal cell carcinoma of the lower eyelid.

We present the clinical case of a 71-year-old woman with a history of multiple basal cell carcinomas (BCC) who presented a nodular lesion in practically the entire extension of the free edge of the lower eyelid. The lesion was approached by excision of the palpebral margin with limited vertical resection of the tarsus and Tripier flap with a correct aesthetic and functional result, free histological margins and no recurrence in a 12-month follow-up.

Morphological description and molecular characterization of Ancyracanthus electrophori n. sp. (Gnathostomatoidea: Gnathostomatidae): a new nematode parasitic in the electric eel Electrophorus varii (Gymnotiformes: Gymnotidae), from the Brazilian Amazon.

A new species of Ancyracanthus, parasite of the electric eel Electrophorus varii, in the Brazilian Amazon, is described based on morphological and molecular characterization. Ancyracanthus electrophori n. sp. differs from the two congeners namely, Ancyracanthus pinnatifidus and Ancyracanthus schubarti, based on the structure of cephalic appendages, number and arrangement of caudal papillae in males, vulva very close to anus in females, eggs with smoothly mamillated shell, host taxon and geographical origin. Moreover, the new species is the first in the genus to be described with thorny cuticular rings and to be observed with the use of scanning electron microscopy (SEM). The morphology of A. pinnatifidus and A. schubarti is still poorly-known and should be revised in details; however, the separation between them and the new species was clear. Genetic characterization based on 28S rDNA and cytochrome c oxidase subunit I (cox1) mtDNA partial sequences, performed for the first time in Acyracanthus, along with phylogenetic reconstructions using both genetic markers, placed Ancyracanthus electrophori n. sp. in a suggestive basal position within Gnathostomatidae. Phylogenetic reconstructions using cox1 sequences also suggested lack of monophyly in the genera Gnathostoma and Spiroxys and, consequently, in the subfamilies Gnathostominae and Spiroxyinae. However, such results are preliminary. With the first genetic characterization and observations using SEM in Ancyracanthus, resulting in the discovery of a new species and in the expansion of the geographical occurrence of the genus to Amazonian fish, an important step towards a better understanding of these nematodes has been taken.

Ceramic shell waste valorization: A new approach to increase the sustainability of the precision casting industry from a circular economy perspective.

The problem of waste generation has grown because of the need to extract natural resources, obtain materials, and consume energy to meet current societal needs. Many studies have been conducted worldwide in favor of technological solutions for the valorization of industrial waste (IW) but few discussed relevant data for effective recovery. In this study, a case study of ceramic shell waste (CSW) was performed using, for the first time, a waste valorization system based on the classification, potentiality, quantity/viability, and applicability criteria (CPQvA) in a specific region (Brazil). CPQvA is a multicriteria decision-making system that acts as a guide to help managers and researchers connect the potential of IW with the feasibility of its application in a product or another process. Using the proposed systematic criteria, it was possible to demonstrate similarities and differences in waste applications. Thirteen possible products made from CSW were analyzed based on all the parameters of CPQvA. Ceramic filters and refractory aggregates were the most viable products. Creating public policies that encourage the use of waste as a raw material could make the precision casting industry process cleaner and the economy more circular.

Diaspore dispersal season influences root growth and seed traits, but not germination responses, of sympatric Piper species in a seasonal forest.

Seeds may differ in terms of dormancy, longevity, sensitivity to desiccation and dry mass, according to the timing (dry season/rainy season) of diaspore dispersal. In addition, seasonal variations in temperature and water availability can act as signals of the season during seed development, influencing germination responses and root growth. We evaluated the effects of temperature variations and water availability on germination parameters, root growth and seed traits of four coexisting Piper species in seasonal vegetation that differed in diaspore dispersal timing. Eight temperature treatments (15, 20, 23, 25, 28, 30, 35 °C, and alternate 30 °C-20 °C) and four induced water potentials (0, -0.3, -0.6 and -1.2 MPa) were used. The parameters germination onset, germination percentage (G%), mean germination time (MGT), root elongation, seed longevity during ex situ storage and dry mass of seeds were evaluated. Germination responses observed were independent of the diaspore dispersal timing, such as variations in germination onset, G% and MGT, both in temperature and water availability treatments. In contrast, root elongation, longevity and dry mass of seeds varied according to the time of diaspore dispersal. Our results corroborate the hypothesis that the timing of diaspore dispersal is an important factor in controlling the initial development of seedlings in seasonal vegetation, but not in germination responses. The predominance of negative effects of temperature increases and water deficit on root growth shows that the initial stages of plant development can be strongly impacted by these environmental factors.

Analysis of relationship of psychosocial factors with patient safety culture in a Brazilian hospital: Study with structural equation modeling analysis.

INTRODUCTION AND OBJECTIVES: The scenario of the health system can develop physical and emotional impacts on health professionals, due to work overload and failure to manage the system. It is necessary to consolidate the theory that the safety of care provided by health services is affected by organizational conditions. The aim of this study is to assess whether safety culture is related to job satisfaction, depressive symptoms, and burnout syndrome among hospital professionals. MATERIALS AND METHODS: This is an analysis with structural equation modeling, conducted in a teaching hospital in Brazil. Data collection was made via psychometric instruments, which sought to analyze job satisfaction (Job Satisfaction Survey), depressive symptoms (Patient Health Questionnaire), burnout syndrome (Maslach Burnout Inventory), as well as the relationship between this factors and patient safety culture (Safety Attitudes Questionnaire). The Pearson correlation coefficient (r) and the partial least squares structural equation modeling (PLS-SEM) were used for analysis. RESULTS: A higher work satisfaction was associated with a higher perception of safety culture (r=0.69; P<0.001). Depressive symptoms and burnout dimensions showed an inverse relationship with the safety culture (P<0.05). PLS-SEM enabled us to understand the behavior of this association. Thus, satisfaction at work and the absence of burnout proved to be predictive factors for the implementation of an ideal patient safety culture (P<0.001). CONCLUSIONS: Patient safety culture is related to job satisfaction and burnout among hospital professionals. These findings suggest that the psychosocial work environment influences the quality of care provided.

Protective role of Portuguese natural mineral waters on skin aging: in vitro evaluation of anti-senescence and anti-oxidant properties.

Natural mineral waters (NMWs) emerge from the earth as springs and their beneficial therapeutic effect has been empirically recognized in different countries. Portugal has diverse NMW resources that are sought for the relief of different afflictions including dermatological complications. However, there is a lack of scientific validation supporting this empiric knowledge. In this study, we aimed to screen the in vitro bioactivity of Portuguese NMWs with different chemical profiles, namely sulfurous/bicarbonate/sodic (SBS), bicarbonate/magnesium, sulfated/calcic, sulfurous/chlorinated/sodic, sulfurous/bicarbonate/fluoridated/sodic, and chlorinated/sodic, focusing on aging-related skin alterations. Mouse skin fibroblasts and macrophages were exposed to culture medium prepared in different NMWs. Cellular viability was evaluated by MTT assay and etoposide-induced senescence was analyzed through the beta-galactosidase staining kit. Wound healing was investigated by the scratch assay, and phototoxicity/photoprotection after UVA irradiation was evaluated using a neutral red solution. ROS production was quantified using the 2'7'-dichlorofluorescin diacetate dye, and the activity of superoxide dismutase (SOD) was analyzed by a commercial kit after lipopolysaccharide exposure. NMWs within the SBS profile demonstrated anti-senescence activity in skin fibroblasts, along with a variable effect on cellular viability. Among the tested NMWs, two decreased cellular senescence and preserved cell viability and were therefore selected for subsequent studies, together with a SBS NMW with therapeutic indications for dermatologic diseases. Overall, the selected NMW promoted wound healing in skin fibroblasts and activated SOD in macrophages, thus suggesting an anti-oxidant effect. None of the NMWs prevented phototoxicity after UV irradiation. Our results shed a light on the anti-aging potential of Portuguese NMW, supporting their putative application in cosmetic or medical products.

Is resveratrol a prospective therapeutic strategy in the co-association of glucose metabolism disorders and neurodegenerative diseases?

Objectives: The mechanism behind the progression of Mild Cognitive Impairment (MCI) to Alzheimer's disease (AD) remains poorly understood. However some evidence pointed out that the co-occurrence of metabolic conditions affecting glucose homeostasis, as type 2 diabetes mellitus (T2DM), may be an important catalyst in this context. Notably, candidate drugs which modulate common pathways in the development of MCI-to-AD mediated by T2DM may offer likely therapy for AD. Nonetheless, limited pharmacological alternatives that modulate common pathways in T2DM, MCI, and AD are available. In the recent decades, studies have shown that resveratrol may act as a neuroprotective compound, but little is known about its potential in improving cognitive and metabolic aspects associated with AD progression mediated by the co-association between TDM2-MCI.Methods: In this review, we discuss possible protective mechanisms of resveratrol on shared pathways associated with AD progression mediated by T2DM-MCI co-occurrence.Results: Some studies indicated that insulin resistance and hyperglycemia may be also a T2DM risk factor for the progression of MCI-to-AD, promoting alterations in metabolic pathways associated with neuronal plasticity, and increasing pro-inflammatory environment. Interestingly, basic research and clinical trials indicate that resveratrol may modulate those pathways, showing a potential neuroprotective effect of this polyphenol.Conclusion: Therefore, there is not enough clinical data supporting the translational therapeutic use of resveratrol in this scenario.

Interactions of gall-formers and leaf-chewers on a tropical tree fern: evidence for non-repulsion and co-occurrence between insect guilds.

Host plant selection by herbivores is driven by a complex array of cues, including leaf traits and previous leaf damage. Herbivore-associated cues to host selection at the plant and leaf scale aid understanding of mechanisms responsible for host preference that might translate into increased performance, as well as processes structuring herbivore populations mediated by interactions. We investigated how changes induced by a galling insect in the tropical fern Cyathea phalerata act as repellent or attractant cues for sawfly feeding and the effects of leaf size on herbivory levels. We recorded gall abundance, damage by chewers, leaf size, plant nutritional quality, phenolic concentration and leaf anatomical traits between galled and non-galled leaf samples. Galled samples contained less N, higher levels of phenolics and higher C/N ratio. However, leaf-chewing damage did not differ between galled and non-galled leaves. The gall structure was avoided by chewers, as it had high concentrations of phenolics, lignification and suberization. Larger leaves sustained higher gall abundance, but leaf size did not have a significant effect on chewer damage. A co-occurrence index calculated for both guilds indicated that galls and chewers exhibited a distribution that did not differ from random, reinforcing that the two guilds on C. phalerata do not show patterns of repulsion such as those maintained by interspecific competition. Sawflies dismissing chemical cues indicate that the increase in phenolics caused by galling insects does not generate increased protection of the galled pinnules. Our results highlight ferns as key resources for herbivores and as a potential plant group to study new research avenues on plant-insect interactions.

Cryo-radiofrequency Stimulates Browning of Adipocytes in Mice.

BACKGROUND: Local fat accumulation is a health risk and this has raised interest in the development of aesthetic treatments, such as cryo-radiofrequency (CRF). OBJECTIVE: To evaluate the consequences of CRF in adipose tissue remodeling in a model system. MATERIALS AND METHODS: Lean and high-fat diet-induced obese mice were assessed 7 days after one CRF application; and lean mice were assessed 0, 3, 6 and 12 h after one application of CRF. Assessments included histology, DNA degradation, gene expression, ELISA of cytokines, serum analysis and neutrophil presence. RESULTS: Unchanged fat mass was found 7 days after CRF in obese and lean mice. However, lean mice showed smaller adipocyte size with areas resembling a browning process. TNF levels, apoptotic cells, and UCP-1 expression increased 7 days after CRF in inguinal adipose tissue of lean mice. Although no differences were found in fat mass, adipocyte size decreased just after CRF and this changed was maintained until 12 h, with cells resembling beige adipocytes. CONCLUSION: We suggest that CRF therapy is capable of inducing thermogenic adipocytes in lean mice.

The MAPKinase Signaling and the Stimulatory Protein-1 (Sp1) Transcription Factor Are Involved in the Phototherapy Effect on Cytokines Secretion from Human Bronchial Epithelial Cells Stimulated with Cigarette Smoke Extract.

The present study was aimed to investigate the phototherapy effect with low-level laser on human bronchial epithelial cells activated by cigarette smoke extract (CSE). Phototherapy has been reported to actuate positively for controlling the generation/release of anti-inflammatory and pro-inflammatory mediators from different cellular type activated by distinct stimuli. It is not known whether the IL-8 and IL-10 release from CSE-stimulated human bronchial epithelium (BEAS) cells can be influenced by phototherapy. Human bronchial epithelial cell (BEAS) line was cultured in a medium with CSE and irradiated (660 nm) at 9 J. Apoptosis index was standardized with Annexin V and the cellular viability was evaluated by MTT. IL-8, IL-10, cAMP, and NF-κB were measured by ELISA as well as the Sp1, JNK, ERK1/2, and p38MAPK. Phototherapy effect was studied in the presence of mithramycin or the inhibitors of JNK or ERK. The IL-8, cAMP, NF-κB, JNK, p38, and ERK1/2 were downregulated by phototherapy. Both the JNK and the ERK inhibitors potentiated the phototherapy effect on IL-8 as well as on cAMP secretion from BEAS. On the contrary, IL-10 and Sp1 were upregulated by phototherapy. The mithramycin blocked the phototherapy effect on IL-10. The results suggest that phototherapy has a dual effect on BEAS cells because it downregulates the IL-8 secretion by interfering with CSE-mediated signaling pathways, and oppositely upregulates the IL-10 secretion through of Sp1 transcription factor. The manuscript provides evidence that the phototherapy can interfere with MAPK signaling via cAMP in order to attenuate the IL-8 secretion from CSE-stimulated BEAS. In addition, the present study showed that phototherapy effect is driven to downregulation of the both the IL-8 and the ROS secretion and at the same time the upregulation of IL-10 secretion. Besides it, the increase of Sp-1 transcription factor was crucial for laser effect in upregulating the IL-10 secretion. The dexamethasone corticoid produces a significant inhibitory effect on IL-8 as well as ROS secretion, but on the other hand, the corticoid blocked the IL-10 secretion. Taking it into consideration, it is reasonable to suggest that the beneficial effect of laser therapy on lung diseases involves its action on unbalance between pro-inflammatory and anti-inflammatory mediators secreted by human bronchial epithelial cells through different signaling pathway.

An uncommon case of vulvar cancer metastatic to breast.

Vulvar carcinoma corresponds to the fourth gynecological malignancy in incidence, with more than forty thousand new cases being estimated worldwide in 2020. It is a disease characterized by locoregional spread presenting high recurrence rates although distant metastases are an uncommon event. The purpose of this work is to describe the diagnosis, treatment, and clinical course of vulvar carcinoma in a patient who presented regional recurrences and late metastasis to the mammary gland. Vulvar cancer is a disease with a well-defined natural history; but with the advancement of therapeutic possibilities in recent years, it has been possible to improve the prognosis, reducing the chance of locoregional recurrence. Thus, the possibility of distance recurrence must be remembered in inpatient follow-up with locally advanced vulvar carcinoma, even if atypically, as in the case reported.

When rice gets the chills: comparative transcriptome profiling at germination shows WRKY transcription factor responses.

Rice is vital for food security. Due to its tropical origin, rice suffers from cold temperatures that affect its entire life cycle. Key genes have been identified involved in cold tolerance. WRKYs are generally downstream of the MAPK cascade and can act together with VQ proteins to regulate stress-responsive genes. Chilling treatment was applied at germination to two rice genotypes (tolerant and sensitive). Shoots at S3 stage were collected for RNA-seq to identify OsWRKY, OsMAPKs and OsVQs expression. Relationships among MAPKs, WRKYs and VQs were predicted through correlation analysis. OsWRKY transcriptional regulation was predicted by in silico analysis of cis-regulatory elements. A total of 39 OsWRKYs were differentially expressed. OsWRKY21, OsWRK24 and OsWRKY69 are potential positive regulators, while OsWRKY10, OsWRK47, OsWRKY62, OsWRKY72 and OsWRKY77 are potential negative regulators, of chilling tolerance. 12 OsMAPKs were differentially expressed. OsMAPKs were downregulated and negatively correlated with the upregulated OsWRKYs in the tolerant genotype. 19 OsVQs were differentially expressed, three and six OsVQs were positively correlated with OsWRKYs in the tolerant and sensitive genotypes, respectively. Seven differentially expressed OsWRKYs have cold-responsive elements in their promoters and five upregulated OsWRKYs in the tolerant genotype contained the W-box motif. Chilling causes changes in OsWRKY, OsMAPK and OsVQ gene expression at germination. OsWRKYs may not act downstream of the MAPK cascade to coordinate chilling tolerance, but OsWRKYs may act with VQs to regulate chilling tolerance. Candidate OsWRKYs are correlated and have a W-box in the promoter, suggesting an auto-regulation mechanism.