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1.
Nat Commun ; 12(1): 3724, 2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34140487

RESUMO

The origin of the weak insulating behavior of the resistivity, i.e. [Formula: see text], revealed when magnetic fields (H) suppress superconductivity in underdoped cuprates has been a longtime mystery. Surprisingly, the high-field behavior of the resistivity observed recently in charge- and spin-stripe-ordered La-214 cuprates suggests a metallic, as opposed to insulating, high-field normal state. Here we report the vanishing of the Hall coefficient in this field-revealed normal state for all [Formula: see text], where [Formula: see text] is the zero-field superconducting transition temperature. Our measurements demonstrate that this is a robust fundamental property of the normal state of cuprates with intertwined orders, exhibited in the previously unexplored regime of T and H. The behavior of the high-field Hall coefficient is fundamentally different from that in other cuprates such as YBa2Cu3O6+x and YBa2Cu4O8, and may imply an approximate particle-hole symmetry that is unique to stripe-ordered cuprates. Our results highlight the important role of the competing orders in determining the normal state of cuprates.

2.
Nat Commun ; 11(1): 3323, 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620752

RESUMO

In underdoped cuprates, the interplay of the pseudogap, superconductivity, and charge and spin ordering can give rise to exotic quantum states, including the pair density wave (PDW), in which the superconducting (SC) order parameter is oscillatory in space. However, the evidence for a PDW state remains inconclusive and its broader relevance to cuprate physics is an open question. To test the interlayer frustration, the crucial component of the PDW picture, we perform transport measurements on charge- and spin-stripe-ordered La1.7Eu0.2Sr0.1CuO4 and La1.48Nd0.4Sr0.12CuO4 in perpendicular magnetic fields (H⊥), and also with an additional field applied parallel to CuO2 layers (H∥). We detect several phenomena predicted to arise from the existence of a PDW, including an enhancement of interlayer SC phase coherence with increasing H∥. These data also provide much-needed transport signatures of the PDW in the regime where superconductivity is destroyed by quantum phase fluctuations.

3.
Sci Adv ; 5(6): eaav7686, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31214648

RESUMO

Do charge modulations compete with electron pairing in high-temperature copper oxide superconductors? We investigated this question by suppressing superconductivity in a stripe-ordered cuprate compound at low temperature with high magnetic fields. With increasing field, loss of three-dimensional superconducting order is followed by reentrant two-dimensional superconductivity and then an ultraquantum metal phase. Circumstantial evidence suggests that the latter state is bosonic and associated with the charge stripes. These results provide experimental support to the theoretical perspective that local segregation of doped holes and antiferromagnetic spin correlations underlies the electron-pairing mechanism in cuprates.

4.
J Fr Ophtalmol ; 41(5): 447-452, 2018 May.
Artigo em Francês | MEDLINE | ID: mdl-29778284

RESUMO

INTRODUCTION: Uveitis is the leading cause of acquired childhood blindness with a prevalence of 30 cases per 100,000 inhabitants. There are multiple causes ; nevertheless, there is no standardized etiological assessment. The goal of our study is to define an epidemiological and clinical profile of uveitis diagnosed in a university hospital and their course when treated with anti-tumor necrosis factor (TNF) α. PATIENTS AND METHODS: All cases of uveitis under 18 years old, from 1994 to 2016, were included. Post-traumatic, post-surgical, pseudo-uveitis and retinopathy of prematurity were excluded. Demographic data, patient history, initial ophthalmological status, etiologic assessment data and treatments already underway were collected. RESULTS: Ninety cases of pediatric uveitis were included, among which were 16.7 % infectious uveitis, 38.9 % inflammatory uveitis and 44.4 % idiopathic uveitis. Etiologic investigations were considered incomplete in 45 % of idiopathic uveitis cases. Treatment with anti-TNFα was selected for 15.5 % of patients. In total, 33 % of patients treated with etanercept required other anti-TNFα drugs due to a lack of control of inflammation. Infliximab and adalimumab successfully managed to control inflammation in 28.6 % of cases each. DISCUSSION: Diagnostic criteria based adult systemic disease are sometimes inappropriate for children. The advent of anti-TNFα appears to improve the visual prognosis of inflammatory uveitis resistant to conventional immunosuppressant therapy, but we still need to perfect protocols for their use. CONCLUSION: There are neither standardized etiological assessment nor clear diagnostic and therapeutic protocols for children. TNFα inhibitors are more effective in controlling inflammation in severe pediatric uveitis.


Assuntos
Imunossupressores/uso terapêutico , Fator de Necrose Tumoral alfa/imunologia , Uveíte/tratamento farmacológico , Uveíte/epidemiologia , Adalimumab/uso terapêutico , Adolescente , Idade de Início , Criança , Pré-Escolar , Progressão da Doença , Etanercepte/uso terapêutico , Feminino , Humanos , Infliximab/uso terapêutico , Masculino , Estudos Retrospectivos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Uveíte/patologia
5.
J Phys Condens Matter ; 30(24): 245801, 2018 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-29722680

RESUMO

We report a systematical structural, transport and magnetic study of Ca or Ba doped Sr2IrO4 single crystals. Isoelectronically substituting Ca2+ (up to 15%) or Ba2+ (up to 4%) ion for the Sr2+ ion provides no additional charge carriers but effectively changes the lattice parameters in Sr2IrO4. In particular, 15% Ca doping considerably reduces the c-axis and the unit cell by nearly 0.45% and 1.00%, respectively. These significant, anisotropic compressions in the lattice parameters conspicuously cause no change in the Néel temperature which remains at 240 K, but drastically reduces the electrical resistivity by up to five orders of magnitude or even precipitates a sharp insulator-to-metal transition at lower temperatures, i.e. the vanishing insulating state accompanies an unchanged Néel temperature in (Sr1-x A x )2IrO4. This observation brings to light an intriguing difference between chemical pressure and applied pressure, the latter of which does suppress the long-range magnetic order in Sr2IrO4. This difference reveals the importance of the Ir1-O2-Ir1 bond angle and homogenous volume compression in determining the magnetic ground state. All results, along with a comparison drawn with results of Tb and La doped Sr2IrO4, underscore that the magnetic transition plays a nonessential role in the formation of the charge gap in the spin-orbit-tuned iridate.

6.
Phys Rev Lett ; 120(1): 017201, 2018 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-29350946

RESUMO

Electrical control of structural and physical properties is a long-sought, but elusive goal of contemporary science and technology. We demonstrate that a combination of strong spin-orbit interactions (SOI) and a canted antiferromagnetic Mott state is sufficient to attain that goal. The antiferromagnetic insulator Sr_{2}IrO_{4} provides a model system in which strong SOI lock canted Ir magnetic moments to IrO_{6} octahedra, causing them to rigidly rotate together. A novel coupling between an applied electrical current and the canting angle reduces the Néel temperature and drives a large, nonlinear lattice expansion that closely tracks the magnetization, increases the electron mobility, and precipitates a unique resistive switching effect. Our observations open new avenues for understanding fundamental physics driven by strong SOI in condensed matter, and provide a new paradigm for functional materials and devices.

7.
Phys Rev Lett ; 118(2): 027202, 2017 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-28128620

RESUMO

We use resonant elastic and inelastic x-ray scattering at the Ir-L_{3} edge to study the doping-dependent magnetic order, magnetic excitations, and spin-orbit excitons in the electron-doped bilayer iridate (Sr_{1-x}La_{x})_{3}Ir_{2}O_{7} (0≤x≤0.065). With increasing doping x, the three-dimensional long range antiferromagnetic order is gradually suppressed and evolves into a three-dimensional short range order across the insulator-to-metal transition from x=0 to 0.05, followed by a transition to two-dimensional short range order between x=0.05 and 0.065. Because of the interactions between the J_{eff}=1/2 pseudospins and the emergent itinerant electrons, magnetic excitations undergo damping, anisotropic softening, and gap collapse, accompanied by weakly doping-dependent spin-orbit excitons. Therefore, we conclude that electron doping suppresses the magnetic anisotropy and interlayer couplings and drives (Sr_{1-x}La_{x})_{3}Ir_{2}O_{7} into a correlated metallic state with two-dimensional short range antiferromagnetic order. Strong antiferromagnetic fluctuations of the J_{eff}=1/2 moments persist deep in this correlated metallic state, with the magnon gap strongly suppressed.

9.
Sci Rep ; 6: 25967, 2016 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-27193161

RESUMO

We have synthesized thermodynamically metastable Ca2IrO4 thin-films on YAlO3 (110) substrates by pulsed laser deposition. The epitaxial Ca2IrO4 thin-films are of K2NiF4-type tetragonal structure. Transport and optical spectroscopy measurements indicate that the electronic structure of the Ca2IrO4 thin-films is similar to that of Jeff = 1/2 spin-orbit-coupled Mott insulator Sr2IrO4 and Ba2IrO4, with the exception of an increased gap energy. The gap increase is to be expected in Ca2IrO4 due to its increased octahedral rotation and tilting, which results in enhanced electron-correlation, U/W. Our results suggest that the epitaxial stabilization growth of metastable-phase thin-films can be used effectively for investigating layered iridates and various complex-oxide systems.

10.
Phys Rev Lett ; 112(14): 147201, 2014 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-24766006

RESUMO

We report x-ray resonant magnetic scattering and resonant inelastic x-ray scattering studies of epitaxially strained Sr2IrO4 thin films. The films were grown on SrTiO3 and (LaAlO3)0.3(Sr2AlTaO6)0.7 substrates, under slight tensile and compressive strains, respectively. Although the films develop a magnetic structure reminiscent of bulk Sr2IrO4, the magnetic correlations are extremely anisotropic, with in-plane correlation lengths significantly longer than the out-of-plane correlation lengths. In addition, the compressive (tensile) strain serves to suppress (enhance) the magnetic ordering temperature TN, while raising (lowering) the energy of the zone-boundary magnon. Quantum chemical calculations show that the tuning of magnetic energy scales can be understood in terms of strain-induced changes in bond lengths.

11.
Phys Rev Lett ; 112(5): 056402, 2014 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-24580616

RESUMO

We synthesize and study single crystals of a new double-perovskite Sr2YIrO6. Despite two strongly unfavorable conditions for magnetic order, namely, pentavalent Ir5+(5d4) ions which are anticipated to have Jeff=0 singlet ground states in the strong spin-orbit coupling (SOC) limit and geometric frustration in a face-centered cubic structure formed by the Ir5+ ions, we observe this iridate to undergo a novel magnetic transition at temperatures below 1.3 K. We provide compelling experimental and theoretical evidence that the origin of magnetism is in an unusual interplay between strong noncubic crystal fields, local exchange interactions, and "intermediate-strength" SOC. Sr2YIrO6 provides a rare example of the failed dominance of SOC in the iridates.

12.
Clin Nephrol ; 69(4): 279-84, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18397702

RESUMO

Our daily dialysis program was started in September 2002: in-center daily on-line hemodiafiltration (DIH) was carried out in 3-hour sessions, 5 - 6 times weekly, on-line assessment KT/Vurea of minimal 1.5 per session, polysulfone membranes. 12 children were included: median age 7.4 years (2.10 - 16.8 years), renal residual function less than 3 ml/min/1.73 m2 (Kcreat + Kurea/2), vascular access central catheter (n = 4) or fistula (n = 8), 7/12 being converted from peritoneal dialysis to DIH. Median follow-up on DIH was 11 months (4 - 43 months), endpoint was kidney transplantation (11/12) or transfer to another center (1/12). Monthly assessments of dialysis parameters (KT/Vurea, predialysis phosphatemia), diet survey (3 consecutive days), medications (number of antihypertensive drugs, phosphate chelators, potassium chelators) and statural growth were performed. At start of DIH, diet intake due to medical prescription and limited appetite was restrictive with limitation in water, salt (20 mmol/day), potassium and proteins (median 35 g/day, range 20 - 80 g); only 2/12 children were free of antihypertensive drugs, all received phosphate and potassium chelators, and growth retardation occurred (7/12 in prepubertal children, median height SDS -1.52) despite rhGH therapy (5/12 patients). At the end of DIH, diet was free, protein intake high (2 - 3 g/kg/day, range 30 - 100), 10/12 children were free of antihypertensive drugs, 4/12 received potassium chelators, 1/12 received phosphate chelators. All the prepubertal children at inclusion (n = 7) showed catch-up growth with a median growth rate of 0.8 cm/month (0.5 - 1.6 cm/ month). DIH allowed to maintain predialysis phosphatemia in a low normal range (median 1.23 mmol/l, range 1.65 - 0.63), without (11/12 children) need of phosphate chelators. Thanks to DIH children, parents and team care discovered during DIH a new way of life with motivated children, showing natural compliance (no diet restriction, no or few drugs), and most of all children developing with catch-up of growth.


Assuntos
Crescimento , Hemodiafiltração/métodos , Falência Renal Crônica/fisiopatologia , Adolescente , Criança , Pré-Escolar , Humanos , Falência Renal Crônica/terapia , Resultado do Tratamento
13.
Acta Histochem ; 110(1): 66-75, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18035401

RESUMO

Ganglioside GM3(Neu5Ac) expression is highly increased in liver 54h following 15% partial hepatectomy in pre-operatively oxygenated rats. GM3(Neu5Gc), GM2, GalNAc-GM1b and gangliosides of the neolacto-series are less affected. GM3(Neu5Ac) is a potent inhibitor of epidermal growth factor signaling. Since GM3(Neu5Ac) growth inhibitory effect depends on its cellular localization, the aim of this study was to detect ganglioside cellular localization during liver regeneration. The experiment was performed using the same rat model which previously showed increased ganglioside expression and more efficient liver regeneration. Frozen sections of liver were analyzed using confocal microscopy after labeling for binding of five ganglioside-specific antibodies, with or without hepatocyte membrane permeabilization. Ganglioside precursors, ceramide (Cer), monohexaosylceramide and lactosylceramide (LacCer) were determined by high-performance thin-layer chromatography. Apoptosis was assessed by fluorescein-dUTP end-labeling of fragmented DNA. Liver of pre-operative oxygenated rats showed high perinuclear labeling of GM3(Neu5Ac) which was absent in post-operative oxygenated and control animals. In the same group, Cer content was lower, monohexaosylceramide and LacCer were absent, and content of apoptotic cells was significantly the lowest, compared to other groups examined (F=20.36, p=0.0001). These findings indicate that ganglioside GM3(Neu5Ac) may be involved in mediation of beneficial effects of pre-operatively oxygenation during the liver regeneration.


Assuntos
Gangliosídeos/análise , Imuno-Histoquímica/métodos , Fígado/efeitos dos fármacos , Oxigênio/farmacologia , Animais , Apoptose/efeitos dos fármacos , Ceramidas/análise , Cromatografia Líquida de Alta Pressão , Hepatectomia/métodos , Fígado/metabolismo , Fígado/fisiopatologia , Regeneração Hepática/efeitos dos fármacos , Microscopia Confocal , Ratos , Ratos Wistar
14.
Biochem Soc Trans ; 35(Pt 5): 942-5, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17956251

RESUMO

The NF-kappaB (nuclear factor kappaB) transcription factors control cell survival, proliferation and innate and adaptive immune response. Post-translational modifications of key components of the NF-kappaB pathway provide the molecular basis for signal transmission from the cell membrane to the nucleus. Here, we describe the involvement of different types of ubiquitin modification in the regulation of the NF-kappaB signalling pathway.


Assuntos
NF-kappa B/metabolismo , Transdução de Sinais , Ubiquitina/metabolismo , Membrana Celular/metabolismo , Núcleo Celular/metabolismo
15.
Clin Genet ; 70(2): 156-60, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16879199

RESUMO

Factors underlying genetic predisposition for development of sporadic colorectal cancer are largely unknown. The fact that this cancer is more common in patients suffering from inflammatory bowel disease raises the question of the relationship between chronic inflammation and cancer. Toll-like receptors 2 (TLR2) and 4 (TLR4) are critical in initiating innate immune response and inflammation toward various bacteria commonly found in the intestine. Recent evidence about the association of polymorphisms in these genes with ulcerative colitis and Crohn's disease, as well as other inflammatory conditions, was the basis for our investigation of their role in sporadic colorectal cancer. We assessed genotype and allele frequencies of TLR2 GT microsatelite polymorphism, TLR2 Arg753Gln, TLR4 Asp299Gly and TLR4 Thr399Ile polymorphisms in 89 colorectal cancer patients and 88 age- and sex-matched controls. The frequency of TLR2 GT microsatelite alleles with 20 and 21 GT repeats was decreased (p = 0.0044 and p = 0.001, respectively), while the frequency of the allele with 31 GT repeats was increased (p = 0.0147) in patients. The mutant allele Asp299Gly of TLR4 gene was slightly more frequent in colorectal cancer patients (p = 0.0269). In conclusion, we report an association of microsatelite GT polymorphisms of TLR2 gene and Asp299Gly polymorphism of the TLR4 gene with sporadic colorectal cancer among Croatians.


Assuntos
Neoplasias Colorretais/genética , Receptor 2 Toll-Like/genética , Idoso , Croácia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Polimorfismo Genético , Receptor 4 Toll-Like/genética
16.
Pediatr Nephrol ; 18(10): 976-80, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12898379

RESUMO

The prescription of peritoneal dialysis should be individualized based on parameters of tolerance and adequacy. Determination of the intraperitoneal fill volume is essential for optimal patient care. Fill volume enhancement is a factor of exchange surface area recruitment: the wetted, contact peritoneal dialysis membrane. Nevertheless, fill volume enhancement can also lead to patient discomfort, with the potential risk of too high an intraperitoneal pressure (hernia, gastro-esophageal reflux). The perception of the individual patient is also a subjective parameter of fill volume tolerance assessment. In contrast, measurement of the hydrostatic intraperitoneal pressure (IPP, cmH(2)O) allows an objective approach to fill volume tolerance. From our clinical experience of more than 10 years of IPP measurements in child care, we can give a recommendation for normal values in children: less than 18 cm of water, usually between 5 and 15 cm, correlated to the intraperitoneal fill volume (naturally), but individually taking into account age, gender, "accustomization" and overall body mass index.


Assuntos
Soluções para Diálise/administração & dosagem , Falência Renal Crônica/terapia , Diálise Peritoneal/métodos , Criança , Humanos , Pressão Hidrostática , Modelos Teóricos
17.
Genet Couns ; 13(3): 289-95, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12416636

RESUMO

Hypophosphatasia is a rare autosomal recessive inborn error of metabolism characterized by a defective bone mineralisation and deficiency of serum and tissue liver/bone/kidney alkaline phosphatase activity. We report the characterisation of tissue-nonspecific alkaline phosphatase (TNSALP) gene mutation in a patient affected by infantile hypophosphatasia. This boy was the first child of non affected, non related parents. At 1 month of age he presented with palsy of the left upper limb with hypotonia. Length was - 2SD. The anterior fontanel was large. There was a markedly decreased ossification of all bones. All limbs were shortened. Ultrasonographic examination of the kidneys showed nephrocalcinosis. Level of alkaline phosphatases was decreased in the child as well as in the parents. Bone density was decreased. At 2 years of age development was delayed. Weight was - 3,5 SD and OFC - 3SD. The child had craniosynostosis. Molecular studies showed 2 missense mutations, both in exon 6 of the TNSALP gene.


Assuntos
Fosfatase Alcalina/genética , Hipofosfatasia/genética , Fosfatase Alcalina/sangue , Aberrações Cromossômicas , Craniossinostoses/diagnóstico por imagem , Mãos/diagnóstico por imagem , Humanos , Hipofosfatasia/complicações , Hipofosfatasia/enzimologia , Hipofosfatasia/fisiopatologia , Lactente , Masculino , Osteocondrodisplasias/diagnóstico por imagem , Radiografia , Raquitismo/etiologia , Raquitismo/fisiopatologia
18.
Endocrinology ; 143(5): 1594-601, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-11956140

RESUMO

This work examines the cellular pathophysiology associated with the weakened bone matrix found in a murine model of osteogenesis imperfecta murine (oim). Histomorphometric analysis of oim/oim bone showed significantly diminished bone mass, and the osteoblast and osteoclast histomorphometric parameters were increased in the oim/oim mice, compared with wild-type (+/+) mice. To assess osteoblast activity, a rat Col1a1 promoter linked to the chloramphenicol acetyltransferase reporter transgene was bred into the oim model. At 8 d and 1 month of age, no difference in transgene activity between oim and control mice was observed. However, at 3 months of age, chloramphenicol acetyl transferase activity was elevated in oim/oim;Tg/Tg, compared with +/+;Tg/Tg and oim/+;Tg/Tg. High levels of urinary pyridinoline crosslinks in the oim/oim;Tg/Tg mice were present at all ages, reflecting continuing high bone resorption. Our data portray a state of ineffective osteogenesis in which the mutant mouse never accumulates a normal quantity of bone matrix. However, it is only after the completion of the rapid growth phase that the high activity of the oim/oim osteoblast can compensate for the high rate of bone resorption. This relationship between bone formation and resorption may explain why the severity of osteogenesis imperfecta decreases after puberty is completed. The ability to quantify high bone turnover and advantages of using a transgene that reflects osteoblast lineage activity make this a useful model for studying interventions designed to improve the bone strength in osteogenesis imperfecta.


Assuntos
Matriz Óssea/fisiologia , Osteoblastos/fisiologia , Osteogênese Imperfeita/genética , Aminoácidos/urina , Animais , Biomarcadores/urina , Desenvolvimento Ósseo/fisiologia , Osso e Ossos/citologia , Cloranfenicol O-Acetiltransferase/biossíntese , Cloranfenicol O-Acetiltransferase/genética , Colágeno Tipo I/genética , Imunofluorescência , Regulação da Expressão Gênica no Desenvolvimento/genética , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Regiões Promotoras Genéticas/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Tíbia/citologia
19.
Pediatr Nephrol ; 17(2): 104-6, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11875672

RESUMO

Recently, cystatin C (cyst C) was proposed for the assessment of glomerular filtration rate, being more accurate than creatinine determination. Reference intervals for cyst C do not vary with age and sex, like creatinine values. Elevated values of cyst C were reported for pre- and full-term infants. Nevertheless, the age cut-off for stable cyst C values i.e., age independence, remains under discussion. Therefore, we conducted a prospective study in 98 healthy children, 51 being under 18 months of age. Cyst C was determined by the nephelometric method. The infants under the age of 18 months had a higher mean serum cyst C value (0.94 +/- 0.24 mg/l) than the older children (0.65 +/- 0.19 mg/l). There was a negative correlation between age and cyst C in the infant group under the age of 18 months (r(2)=0.631, P<0.01). Our results indicate that mean serum cyst C is higher in infants than older children; the age cut-off appears over the age of 1 year of life, presumably reflecting kidney maturation. Our study does not allow accurate assessment of the age cut-off at 18 months or 36 months.


Assuntos
Envelhecimento/sangue , Cistatinas/sangue , Pré-Escolar , Cistatina C , Humanos , Estudos Prospectivos , Valores de Referência
20.
Scand J Immunol ; 55(2): 162-70, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11896932

RESUMO

The jawless Agnatha (lampreys and hagfishes) represent the phylogenetically oldest order of vertebrates that are believed to lack the adaptive immune system of jawed vertebrates. In order to search for molecular markers specific for cellular components of the adaptive immune system in lampreys, we used the polymerase chain reaction (PCR) to identify genes for transcription factors of the Ikaros family in genomic DNA and cDNA libraries from two species of lampreys, Petromyzon marinus and Lampetra fluviatilis. The mammalian Ikaros-like family of transcription factors consists of five members, Ikaros, Helios, Aiolos, Eos and Pegasus, of which the first three appear to be essential for lymphocyte development. Two different Ikaros-like genes, named IKLF1 and IKLF2, were identified in lamprey. They both have the conserved exon-intron structure of seven exons and show alternative splicing like their counterparts in jawed vertebrates. The genes code for predicted proteins of 589 and 513 amino acid residues, respectively. The proteins contain six highly conserved zinc finger motifs that are 83-91% identical to the mammalian members of the Ikaros-like family. The remaining parts of the sequences are, however, mostly unalignable. Phylogenetic analysis based on the alignable segments of the sequences does not identify the orthologous gene in jawed vertebrates but rather shows equidistance of the lamprey Ikaros-like factors to each other and to Ikaros, Helios, Aiolos and Eos. Expression studies by reverse transcription (RT)-PCR and in situ hybridization (ISH), however, provide evidence for moderate expression in presumed lymphoid tissues like the gut epithelium and for high levels of expression in the gonads, especially in the ovary.


Assuntos
Proteínas de Ligação a DNA , Lampreias/genética , Lampreias/imunologia , Fatores de Transcrição/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Sequência Conservada , DNA Complementar/genética , Éxons , Feminino , Expressão Gênica , Fator de Transcrição Ikaros , Íntrons , Masculino , Dados de Sequência Molecular , Ovário/metabolismo , Filogenia , Homologia de Sequência de Aminoácidos , Distribuição Tecidual , Dedos de Zinco/genética
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