Natural fermentation of fresh Jasmine flowers inspired the development of a biotechnological ingredient with global anti-ageing properties.

OBJECTIVE: This study focused on the development of a new-to-world ingredient harnessing the natural potential of fresh Jasminum grandiflorum flowers to self-ferment by its phytobiome revealing flower content. Analytical investigations were conducted to highlight specific phytocompounds generated during the natural fermentation of flowers in comparison to a conventional extraction. The synergy with another extraction technology maximized the generation of biocompounds for an interesting efficacy. METHODS: Jasmine extract was elaborated by combining two patented technologies: the phytofermentology™, inspired by plant-microorganisms interaction and designed to develop ingredients obtained by natural fermentation of the vegetal using its own phytobiota; and the PSR™ technology allowing the extraction of bioactive phytocompounds such as small RNAs from plants. RESULTS: Analytical investigations of Jasmine extract highlighted uniqueness and richness of the phytocompound profiles, such as organics acids and phenolic compounds, markers of fermentation only obtained after phytofermentology in comparison to conventional extraction. Jasmine extract has the particularity to contain jasmintides, flower small peptides belonging to the family of cysteine-rich peptides (CRPs). Antioxidant and global anti-ageing properties were investigated in cell-free assays demonstrating interesting results: about 20% scavenging of free radicals from 0.5% of Jasmine extract and protection from DNA damage of 26% in comparison to a stressed control. CONCLUSION: Phytofermentology™ technology combined with PSR™ technology, meant to be respectful of the environment, allowed to development of biofunctionals very close to nature with a unique analytical signature as Jasmine extract, using the potential of fresh flowers phytobiota to self-ferment. The efficacy of the ingredient on global antioxidation and anti-ageing via hyaluronidase/tyrosinase inhibitions was highlighted by cell-free evaluation assays. Further and complementary studies should be conducted to confirm the bioefficacy of this ingredient with in vitro / ex vivo assays.

Cette étude a pour objectif de développer un nouvel ingrédient unique en exploitant le potentiel des fleurs fraîches de Jasminum grandiflorum à fermenter naturellement en utilisant leur phytobiome, révélant ainsi le contenu de ces fleurs. Des investigations analytiques ont été menées pour mettre en évidence des phytocomposés spécifiques générés lors de la fermentation naturelle des fleurs par rapport à une extraction conventionnelle. La synergie avec une autre technologie d'extraction maximise la génération de biocomposés pour une plus grande efficacité de l'extrait. L'extrait de jasmin a été élaboré en combinant deux technologies brevetées: la phytofermentologie™, inspirée de l'interaction plante/micro­organismes et conçue pour développer des ingrédients obtenus par fermentation naturelle d'un végétal en utilisant son propre phytobiote; et la technologie PSR™ permettant l'extraction de phytocomposés bioactifs tels que les petits ARN des plantes. Les recherches analytiques de l'extrait de jasmin ont mis en évidence le caractère unique et la richesse des profils des différents phytocomposés composant l'extrait, tels que les acides organiques et les composés phénoliques, marqueurs de fermentation obtenus uniquement grâce à la phytofermentologie par rapport à l'extraction conventionnelle. L'extrait de jasmin a la particularité de contenir des jasmintides, petits peptides de fleurs appartenant à la famille des peptides riches en cystéine (CRP). Les propriétés antioxydantes et anti­âge ont été étudiées par des tests acellulaires démontrant des résultats intéressants: environ 20 % d'élimination des radicaux libres à partir de 0,5 % d'extrait de jasmin et une protection contre les dommages à l'ADN de 26 % par rapport à un contrôle stressé. La technologie phytofermentologie™ combinée à la technologie PSR™, se voulant respectueuse de l'environnement, a permis de développer des ingrédients très proches de la nature avec une signature analytique unique comme l'extrait de Jasmin, utilisant le potentiel d'auto­fermentation du phytobiote des fleurs fraîches. L'efficacité de l'ingrédient sur l'antioxydation globale et l'anti­âge via les inhibitions enzymatiques de la hyaluronidase et de la tyrosinase a été mise en évidence par des tests d'évaluation acellulaires. Des études supplémentaires et complémentaires devraient être menées pour confirmer la bioefficacité de cet ingrédient avec des tests in vitro/ex vivo.

The root-knot nematode calreticulin Mi-CRT is a key effector in plant defense suppression.

Root-knot nematodes (RKN) are obligate biotrophic parasites that settle close to the vascular tissues in roots, where they induce the differentiation of specialized feeding cells and maintain a compatible interaction for 3 to 8 weeks. Transcriptome analyses of the plant response to parasitic infection have shown that plant defenses are strictly controlled during the interaction. This suggests that, similar to other pathogens, RKN secrete effectors that suppress host defenses. We show here that Mi-CRT, a calreticulin (CRT) secreted by the nematode into the apoplasm of infected tissues, plays an important role in infection success, because Mi-CRT knockdown by RNA interference affected the ability of the nematodes to infect plants. Stably transformed Arabidopsis thaliana plants producing the secreted form of Mi-CRT were more susceptible to nematode infection than wild-type plants. They were also more susceptible to infection with another root pathogen, the oomycete Phytophthora parasitica. Mi-CRT overexpression in A. thaliana suppressed the induction of defense marker genes and callose deposition after treatment with the pathogen-associated molecular pattern elf18. Our results show that Mi-CRT secreted in the apoplasm by the nematode has a role in the suppression of plant basal defenses during the interaction.

Tobacco rattle virus mediates gene silencing in a plant parasitic root-knot nematode.

Root-knot nematodes (RKNs) are sedentary biotrophic parasites that induce the differentiation of root cells into feeding cells that provide the nematodes with the nutrients necessary for their development. The development of new control methods against RKNs relies greatly on the functional analysis of genes that are crucial for the development of the pathogen or the success of parasitism. In the absence of genetic transformation, RNA interference (RNAi) allows for phenotype analysis of nematode development and nematode establishment in its host after sequence-specific knock-down of the targeted genes. Strategies used to induce RNAi in RKNs are so far restricted to small-scale analyses. In the search for a new RNAi strategy amenable to large-scale screenings the possibility of using RNA viruses to produce the RNAi triggers in plants was tested. Tobacco rattle virus (TRV) was tested as a means to introduce double-stranded RNA (dsRNA) triggers into the feeding cells and to mediate RKN gene silencing. It was demonstrated that virus-inoculated plants can produce dsRNA and siRNA silencing triggers for delivery to the feeding nematodes. Interestingly, the knock-down of the targeted genes was observed in the progeny of the feeding nematodes, suggesting that continuous ingestion of dsRNA triggers could be used for the functional analysis of genes involved in early development. However, the heterogeneity in RNAi efficiency between TRV-inoculated plants appears as a limitation to the use of TRV-mediated silencing for the high-throughput functional analysis of the targeted nematode genes.

ER stress protein AGR2 precedes and is involved in the regulation of pancreatic cancer initiation.

The mechanisms of initiation of pancreatic ductal adenocarcinoma (PDAC) are still largely unknown. In the present study, we analysed the role of anterior gradient-2 (AGR2) in the earliest stages of pancreatic neoplasia. Immunohistochemical analysis of chronic pancreatitis (CP) and peritumoral areas in PDAC tissues showed that AGR2 was present in tubular complexes (TC) and early pancreatic intraepithelial neoplasia (PanINs). Moreover, AGR2 was also found in discrete subpopulations of non-transformed cells neighbouring these pre-neoplastic lesions. In primary cells derived from human patient-derived xenograft (PDX) model, flow-cytometry revealed that AGR2 was overexpressed in pancreatic cancer stem cells (CSC) compared with non-stem cancer cells. In LSL-KrasG12D;Pdx1-Cre (KC) mouse model Agr2 induction preceded the formation of pre-neoplastic lesions and their development was largely inhibited by Agr2 deletion in engineered LSL-KrasG12D;Pdx1-Cre; Agr2-/- mice. In vitro, AGR2 expression was stimulated by tunicamycin-induced endoplasmic reticulum (ER) stress in both KRAS wild-type normal pancreas cells, as well as in KRAS mutated pancreatic cancer cells and was essential for ER homoeostasis. The unfolded protein response proteins GRP78, ATF6 and XBP1s were found expressed in CP and PDAC peritumoral tissues, but in contrast to AGR2, their expression was switched off during TC and PanIN formation. Real-time PCR and ELISA analyses showed that ER stress induced a pro-inflammatory phenotype in pancreatic normal, cancer and stellate cells. Moreover, AGR2 expression was inducible by paracrine transfer of ER stress and pro-inflammation between different pancreatic cell types. Our findings demonstrate that AGR2 induced in ER-stressed and inflammatory pre-neoplastic pancreas is a potential marker of cancer progenitor cells with an important functional role in PDAC initiation.

[A Brazilian multicenter study to evaluate the clinical effectiveness and tolerance of isradipine SRO using ambulatory monitoring of arterial pressure in the treatment of mild and moderate arterial hypertension]. / Estudo multicêntrico brasileiro de avaliação de eficácia clínica e tolerabilidade da isradipina SRO através da monitorização ambulatorial da pressão arterial no tratamento da hipertensão arterial leve e moderada.

PURPOSE: To evaluate clinical efficacy and tolerability of isradipine SRO (I.SRO), 5 mg O.D. in essential hypertensives. METHODS: Eighty-three of 87 selected outpatients with a mean age of 51.3 years (ranging from 25 to 65), 33 male, 48 white, 29 black and others of different races, who had clinical supine and orthostatic diastolic blood pressure (DBP) > or = 95 mmHg and < or = 115 mmHg underwent the study. After a three-week wash-out period, patients received I.SRO 5 mg O.D. at 8:00 am for a six-week period (phase I). After this phase, patients received I.SRO 5 mg O.D. at 8:00 pm for a six-week period (phase II). The patients had a follow-up with an interval of three weeks and the ambulatorial blood pressure monitoring (ABPM) for 24 hours was performed with a SpaceLabs 90207 or Del Mar Avionics devices after the wash-out period and at the end of phases I and II. Measurements were performed at 15-min intervals during the day (6 am to 10 pm) and at 30-min intervals during the night (10 pm to 6 am). RESULTS: a) Heart rate did not show significant changes during the treatment period (phases I and II) when compared with the wash-out period; b) causal blood pressure: at the end of both treatment periods (phases I and II) there were statistically significant decreases (p < 0.001) in supine SBP and DBP compared with wash-out values. The mean SBP decreased from 161.6 +/- 14 to 144.3 +/- 13 mmHg (phase I) and to 141.8 +/- 13 mmHg (phase II). The mean DBP decreased from 103.4 +/- 6 to 91.2 +/- 7 (phase I) and to 89.1 +/- 8 (phase II); c) ABPM: the mean systolic 24-h ambulatory blood pressure was significantly reduced (p < 0.001) from 148.8 +/- 17 to 137.2 +/- 15 mmHg (phase I) and to 133.4 +/- 13 mmHg (phase II). The mean diastolic 24-h ambulatory blood pressure was significantly decreased (p < 0.001) from 94.3 +/- 9 to 87.0 +/- 9 (phase I) and to 85.8 +/- 8 mmHg (phase II). The mean daytime and nighttime, systolic and diastolic 24-h ambulatory blood pressure were: wash-out--152.3 +/- 17, 140.2 +/- 21, 97.4 +/- 9, 86.8 +/- 13; phase I--139.9 +/- 15, 130.0 +/- 17, 89.3 +/- 9, 81.3 +/- 10; phase II--136.7 +/- 13, 125.3 +/- 15, 88.5 +/- 8, 79.1 +/- 10, respectively. Blood pressure load (percentage of systolic blood pressure values > 140 mmHg or of diastolic blood pressure values > 90 mmHg) was significantly reduced from 62.2/62% (SBP/DBP), on the was-out, to 37.9/39.9% (SBP/DBP) on phase I and to 32.3/34.3% (SBP/DBP) on phase II; d) side effects: most frequently related were palpitations (2.3%), headache (1.1%), flush (1%) and ankle oedema (1%). They were in general, mild-to-moderate and disappeared after the first 3 weeks of treatment. Only two patients were withdrawn because of headache (one of them with previous diagnosis of migraine). CONCLUSION: I.SRO, given by oral route, in the dosage of 5 mg O.D. as monotherapy, was effective and well tolerated, promoted significant reduction on 24-h ambulatory blood pressure attenuating the early morning rise and did not interfere with the circadian rhythm of blood pressure. No significant differences were detected in the BP lowering effect when I.SRO was given during the morning or evening. These results may indicate that the drug is as suitable as one of the first choice for treating mild and moderate hypertensive patients.

[Relationship of average level and variability of blood pressure with the geometry of the left ventricle in systemic hypertension]. / Relação do nível médio e variabilidade da pressão arterial com a geometria do ventrículo esquerdo na hipertensão arterial sistêmica.

PURPOSE: To study the relation between the average level and variability of blood pressure (VBP) obtained by ambulatory monitoring (AMBP) and the geometric pattern (GP) of the left ventricle (LV) obtained by echocardiography (ECHO) in patients with hypertension (Hy) METHODS: AMBP and ECHO were performed in 37 patients with Hy, divided into three groups: group A--11 women using antihypertensive therapy (AH); group B--15 men using AH and group C--7 male and 4 female without AH. The GP of LV was obtained by ECHO based on mass index (MI) and relative thickness of the wall (RTW). Mean systolic (MSBP) and diastolic (MDBP) were analyzed during daytime (DT) and nighttime (NT) periods. VBP was defined by mean standard deviation (SD) of mean pressures considered. RESULTS: In G-A, there was a significant association between the MI and both VBP and MSBP (r = 0.65 and p < 0.005, r = 0.61, and p < 0.005, respectively), and MSBP and VBP during the DP (r = 0.64 and p < 0.005, r = 0.75, and p < 0.005). In G-B, there was a relation between the LVRTW (r = 0.55 and p < 0.005), and MSBP during the DP (r = 0.65 and p < 0.005). In G-C, there was a significant association (p < 0.005) between the MI and the MDBP in the DP and with the MSBP in the NP (r valueS ranged from 0.51 to 0.66). There was also a significant relation (p < 0.005) between the LVRTW and the SD of all variables in both DP and NP (r ranged from 0.47 to 0.78 and mean diastolic in the wakeful period (r = 0.42 to 0.78) and MDBP in the DP (r = 0.42 and p < 0.05). CONCLUSION: Both the increase in VBP and the mean BP are involved in the changes of LVGP in Hy.

[Isradipine: a Brazilian multicenter study for the evaluation of the efficacy and safety in the treatment of mild and moderate arterial hypertension]. / Isradipina: estudo multicêntrico brasileiro de avaliação de eficácia e tolerabilidade no tratamento da hipertensão arterial leve e moderada.

PURPOSE: To evaluate the efficacy and tolerability of isradipine, a new dihydropyridine calcium antagonist, in the treatment of mild-to-moderate hypertension. PATIENTS AND METHODS: One hundred and eighty outpatients with different races, who had supine and orthostatic diastolic blood pressure (DBP) > or = 95 mmHg and < or = 115 mmHg, with a mean age of 52.03 +/- 11.47 years, 70 men, 110 women; underwent the study. After a two-week wash-out period patients received isradipine 2.5 mg b.i.d. for 90 days. Follow-up visits were performed at the 30th, 60th and 90th days of treatment. RESULTS: At the end of treatment (90 days), a statistically significant decrease (p < 0.05) in SBP and DBP in supine position was observed. A mean SBP was reduced from 159.28 +/- 16.99 to 142.51 +/- 15.12, and mean DBP declined from 101.49 +/- 6.82 to 86.63 +/- 7.40. Heart rate, weight, electrocardiograms and laboratory tests did not shows significant changes during treatment when compared to baseline evaluation. The most frequent related side effects (headache and dizziness with nausea) were transient, and at the end of the study 96.7% of the patients did not have any complaint. However, two patients were withdrawn from the trial because of important headache. CONCLUSION: Isradipine 2.5 mg by oral route, b.i.d. has shown to be effective and well tolerated in the treatment of mild-to-moderate hypertension in patients of both sexes and several ages and races.

[Evaluation of iron overload in thalassemia]. / La valutazione del sovraccarico di ferro nella talassemia.

The aim of the paper is to assess the value of a series of clinical and laboratory indices used in determining the degree of iron overload in homozygous beta-thalassaemic patients. 155 thalassaemic patients of different age in chelation with subcutaneous infusions of desferrioxamine for a period of 2-7 years have been studied. Calculation of the total iron accumulated and the iron load per kg of body weight in patients undergoing chelation requires an exact knowledge of their compliance and faecal and urinary iron elimination, and is clearly open to many errors. Despite this, usefull information can be derived from its determination. We have found, for example, that serious organ damage tends to appear when iron accumulation exceeds 1 g/kg. In addition, the serum ferritin and the evaluation of the growth have been proved to be the most important and helpful indices for checking the effectiveness of the chelation therapy and forecasting the appearance of the serious complications as diabetes or hypothyroidism.

Genetics of ovarian differentiation: Rspo1, a major player.

In mammals, the sex of the embryo is determined during development by its commitment either to the male or female genetic program regulating testicular or ovarian organogenesis. Major steps towards unraveling sex determination in mammals are achieved by the identification of key genes involved in human pathologies and the application of mouse genetics to analyze their function. While the expression of Sry and Sox9 is sufficient to induce the male developmental program, the molecular pathways that specify ovarian differentiation were unclear before the recent demonstration that mutations in the RSPO1 gene induce female-to-male sex reversal in XX patients. By generating the corresponding mouse model, we have shown that Rspo1 is so far the earliest known gene controlling the female genetic developmental program. Rspo1 activates the canonical beta-catenin signaling pathway required for female somatic cell differentiation and germ cell commitment into meiosis. The aim of this review is to describe the roles of R-spondins (Rspo)in developmental processes and disorders and the current knowledge obtained from murine models. A particular focus will be on Rspo1 and its crucial function in sex determination.

Transcriptome analysis of root-knot nematode functions induced in the early stages of parasitism.

Root-knot nematodes of the genus Meloidogyne are obligate biotrophic parasites able to infest > 2000 plant species. The nematode effectors responsible for disease development are involved in the adaptation of the parasite to its host environment and host response modulation. Here, the differences between the transcriptomes of preparasitic exophytic second-stage juveniles (J2) and parasitic endophytic third-stage juveniles (J3) of Meloidogyne incognita were investigated. Genes up-regulated at the endophytic stage were isolated by suppression subtractive hybridization and validated by dot blots and real-time quantitative polymerase chain reaction (PCR). Up-regulation was demonstrated for genes involved in detoxification and protein degradation, for a gene encoding a putative secreted protein and for genes of unknown function. Transcripts of the glutathione S-transferase gene Mi-gsts-1 were 27 times more abundant in J3 than in J2. The observed Mi-gsts-1 expression in the oesophageal secretory glands and the results of functional analyses based on RNA interference suggest that glutathione S-transferases are secreted during parasitism and are required for completion of the nematode life cycle in its host. Secreted glutathione S-transferases may protect the parasite against reactive oxygen species or modulate the plant responses triggered by pathogen attack.

[Group A streptococci: serotypes isolated in a pediatric environment]. / Streptococchi di gruppo A: sierotipi isolati in ambiente pediatrico.

We examined the incidence of different types of group A Streptococci in children with various (mostly respiratory) diseases. The 85.6% of strains assayed were T typable; they belonged more frequently to "5-11-12-27-44" T complex, to type T12, T1, "3-13-B3264" T complex and T4. An increase of type 1 and 4 was found in streptococcal strains isolated more recently.

Streptococcal receptors for human immunoglobulins.

Six streptococcus strains with a high affinity for human serum Ig were examined under various experimental conditions to correlate their structures with specific IgG and IgA receptors. Treatment at 80 degrees C for 5 min appeared to have no effect on their ability to bind IgG and/or IgA, while long maintenance in culture determined a dissimilar partial loss of IgG and IgA binding ability. Proteolytic enzymes and hot HCl reduced the ability of these strains, especially those in group A, to absorb both IgG and IgA. It would seem that the protein most involved in this type of bond is the T protein.

Clinical efficacy and tolerability of isradipine in the treatment of mild-to-moderate hypertension in young and elderly patients.

The clinical efficacy and tolerability of isradipine was evaluated in 63 patients with mild-to-moderate hypertension [supine systolic blood pressure (SBP) greater than or equal to 160 mm Hg and diastolic blood pressure (DBP) greater than or equal to 95 mm Hg]. Patients were divided into two groups according to age: group A (n = 41), aged 37-69 years (mean age of 54 +/- 7 years); group B (n = 22), aged 70-80 years (mean age of 72.8 +/- 2.4 years). After a 3-week washout period, group A received 2.5 mg of isradipine twice daily for 6 weeks. Group B received 1.25 mg of isradipine initially, increasing to 2.5 mg twice daily according to treatment response and tolerability. At the end of treatment (week 6), there were statistically significant decreases (p less than 0.01) in supine SBP and DBP in both groups compared with baseline values: the mean SBP in groups A and B decreased from 160.0 +/- 14.7 to 133.6 +/- 10.0 mm Hg and from 161.6 +/- 17.8 to 134.8 +/- 10.9 mm Hg, respectively; the mean DBP in groups A and B decreased from 101.3 +/- 3.0 to 83.6 +/- 5.5 mm Hg and from 101.3 +/- 8.4 to 84.2 +/- 3.6 mm Hg, respectively. Clinical and laboratory parameters did not change significantly during treatment. Side effects (headache, flushing, palpitations, and edema) were mild/moderate and disappeared after the first 2 weeks of treatment. In conclusion, 2.5 mg of isradipine twice daily is effective and well tolerated in the treatment of mild-to-moderate hypertension regardless of patient age.

Suicide attempts in patients with systemic lupus erythematosus.

BACKGROUND: Suicide and suicide attempts, although well recognised in patients with systemic lupus erythematosus (SLE), have been commented on relatively little. OBJECTIVE: To obtain a better understanding of the reasons for suicidal behaviour in patients with SLE. METHODS: The records of 300 patients with SLE were reviewed to identify completed or attempted suicides. RESULTS: Five patients made seven attempts at suicide over a 20 year follow up period; one of them was fatal. All of those attempting suicide had a history of neuropsychiatric SLE (NPSLE) presenting with depression and they made the attempts soon after the onset of NPSLE (median time 12.5 months). Two patients had appreciable disease activity at the time of the suicide attempt. Lymphopenia was present in five suicide attempts. Anti-SSA/Ro antibodies were detected in three patients, none of whom had anti-SSB/La. All patients apart from one responded to treatment for depression; the remaining female patient made two subsequent suicide attempts, with a fatal outcome despite intensive treatment. CONCLUSION: Greater awareness of the risk of suicide in patients with psychiatric manifestations of SLE may help to reduce the incidence of this potentially fatal phenomenon.

Pax8 has a key role in thyroid cell differentiation.

Transformation of rat thyroid cells with polyoma virus middle T antigen results in loss of the thyroid-differentiated phenotype, measured as the expression of the thyroglobulin (Tg), thyroperoxidase (TPO), and sodium/iodide symporter (NIS) genes. Among the transcription factors involved in the regulation of these genes, TTF-1 and TTF-2 were still detected at nearly wild-type levels, while a specific loss of the paired domain transcription factor Pax8 was observed. In this study, we used the PCPy cell line as a model system to study the role of Pax8 in thyroid differentiation. We demonstrate that the reintroduction of Pax8 in PCPy cells is sufficient to activate expression of the endogenous genes encoding thyroglobulin, thyroperoxidase, and sodium/iodide symporter. Thus, this cell system provides direct evidence for the ability of Pax8 to activate transcription of thyroid-specific genes at their chromosomal locus and strongly suggests a fundamental role of this transcription factor in the maintenance of functional differentiation in thyroid cells. Moreover, we show that Pax8 and TTF-1 cooperate in the activation of the thyroglobulin promoter and that additional thyroid-specific mechanism(s) are involved in such a cooperation. To identify the Pax8 domain able to mediate the specific activation of the thyroglobulin promoter, we transfected in PCPy cells three different Pax8 isoforms. The results of such experiments indicate that for the transcriptional activation of thyroid-specific genes, Pax8 uses an as yet unidentified functional domain.

[Capacity of some streptococcal strains to absorb in a specific manner, fractions of human blood]. / Capacita' di alcuni ceppi di streptococchi di assorbire in modo specifico frazioni del siero umano.

We valued the capacity to bind immunoglobulins (Ig) G, M and A, albumin, haptoglobin and beta-lipoproteins of human serum by 80 strains of Streptococcus pyogenes and 30 other Streptococci groups. Specific binding were observed between Streptococci belonging to group A, C and G and some serum proteins. The binding varied remarkably among strains. The elevated capacity demonstrated by some strains to absorb IgG and IgA (and in poor degree (IgM) seems particularly interesting. It seems that this binding does not depend on the growth phase of microorganisms, also if the absorption in some cases can be greater in fixed time.

The thyroid transcription factor 2 (TTF-2) is a promoter-specific DNA-binding independent transcriptional repressor.

The thyroid transcription factor TTF-2 is a forkhead-containing protein involved in thyroid-specific gene expression and necessary for thyroid morphogenesis. In this paper, we demonstrate that TTF-2 is able to inhibit the activity of the thyroid-specific transcription factors TTF-1 and Pax-8 only on certain promoters. We identified the minimal protein domain responsible for repressor activity, which behaves as an independent functional domain, and we show that repression by TTF-2 is DNA-binding independent. We suggest that TTF-2 is able to interfere with a specific cofactor required for TTF-1 and Pax-8 activity.