Transcription factors (TFs) regulate gene expression through binding to cis-regulatory specific sequences in the promoters of their target genes. In contrast to the genetic code, the transcriptional regulatory code is far from being deciphered and is determined by sequence specificity of TFs, combinatorial cooperation between TFs and chromatin competence. Here we addressed one of these determinants by characterizing the target sequence specificity of 63 plant TFs representing 25 families, using protein-binding microarrays. Remarkably, almost half of these TFs recognized secondary motifs, which in some cases were completely unrelated to the primary element. Analyses of coregulated genes and transcriptomic data from TFs mutants showed the functional significance of over 80% of all identified sequences and of at least one target sequence per TF. Moreover, combining the target sequence information with coexpression analysis we could predict the function of a TF as activator or repressor through a particular DNA sequence. Our data support the correlation between cis-regulatory elements and the sequence determined in vitro using the protein-binding microarray and provides a framework to explore regulatory networks in plants.T ranscription factors (TFs) mediate cellular responses through recognizing specific cis-regulatory DNA sequences at the promoters of their targets genes. In plants, organ development is a continuous process that expands beyond the embryonic phase and, as sessile organisms, plants have to face with a wide range of environmental stresses. Signaling cascades governing developmental and stress switches converge at the gene expression level. Pioneering work (1) suggested that transcriptional regulation may play more important roles in plants than in animals, given the large number of TF-coding genes in plant genomes, ranging from 6% to 10%, depending on the database.During the last few years, the advance in the determination of TF-binding sites, including both in vivo and in vitro techniques, is helping to decipher the transcriptional regulatory code (2-4). In vivo approaches involving immunoprecipitation of TF-bound chromatin followed by microarray or sequencing analysis (ChIPchip and ChIP-seq, respectively) are contributing to the knowledge of the transcriptional networks associated with a TF. ChIP-based techniques revealed that TFs may bind to thousands of genomic fragments, suggesting that the TF is interacting indirectly with DNA or that the binding requires additional cooperative factors (5, 6). The situation may not be different in the case of plant genomes. To date, only a limited number of studies have deepened in the discovery of the targets of some TFs and found that, similar to TFs in animals, TFs in plants bind to hundreds or thousands of DNA fragments; in some cases, only a small proportion of targets respond transcriptionally to the TF, obscuring the identification of actual binding sites (7-9). In this context, the precise identification of the DNA-binding sequence of each TF may be ins...

Despite significant advances in pharmacologic therapy of depression over the past two decades, a substantial proportion of patients fail to respond or experience only partial response to serotonin re-uptake inhibitor antidepressants, resulting in chronic functional impairment. There appears to be a pattern of symptoms that are inadequately addressed by serotonergic antidepressants - loss of pleasure, loss of interest, fatigue and loss of energy. These symptoms are key to the maintenance of drive and motivation. Although these symptoms are variously defined, they are consistent with the concept of ;decreased positive affect'. Positive affect subsumes a broad range of positive mood states, including feelings of happiness (joy), interest, energy, enthusiasm, alertness and self-confidence. Although preliminary, there is evidence to suggest that antidepressants that enhance noradrenergic and dopaminergic activity may afford a therapeutic advantage over serotonergic antidepressants in the treatment of symptoms associated with a reduction in positive affect. Dopaminergic and noradrenergic agents, including the dual acting norepinephrine and dopamine re-uptake inhibitors, have demonstrated antidepressant activity in the absence of serotonergic function, showing similar efficacy to both tricyclic and serotonin re-uptake inhibitor antidepressants. Moreover, the norepinephrine and dopamine re-uptake inhibitor bupropion has been shown to significantly improve symptoms of energy, pleasure and interest in patients with depression with predominant baseline symptoms of decreased pleasure, interest and energy. Focusing treatment on the predominant or driving symptomatology for an individual patient with major depression could potentially improve rates of response and remission.

Although temperament and personality traits could influence the development and course of eating disorders, only a few studies examined the similarities and differences in personality between anorexia and bulimia nervosa. We compared 72 patients with DSM-IV eating disorders and 30 healthy controls. Dimensions of personality and personality disorders were evaluated with the Eysenck's EPQ, Cloninger's TCI, and the SCID-II questionnaires. The rates of impulsivity and clinical features were evaluated using specific rating scales. A comorbid personality disorder was found in 61.8% of patients with eating disorder. Avoidant personality disorder appeared was relatively common in anorexia nervosa restricting type; borderline personality disorder was most frequent in bulimia nervosa and the binge eating-purging type of anorexia nervosa. From a dimensional perspective, anorexic patients presented high scores in the dimension of persistence. Higher harm avoidance and impulsivity was found in bulimic patients. The overall eating disorders group presented high scores in neuroticism and low scores in self-directedness. Eating disorder patients have heterogeneous features of temperament and personality traits. Cluster C personality disorders seem more common in anorexia nervosa restricting type and impulsive personality features are associated with bulimic symptoms. Impulsivity seems to be a key aspect of temperament of bulimic patients, whereas anorexic symptoms are linked to persistent temperament traits.

Cytogenetic analysis of unstimulated short‐term bone marrow cell cultures was performed on 280 patients with multiple myeloma and related disorders. In 65% of the cases, an additional short term B‐cell stimulated culture was also examined. Chromosomally abnormal clones were found in 31% of the patients, 15% in Waldenström macroglobulinemia, 25% in monoclonal gammopathies, 33% in multiple myeloma, and 50% in plasma cell leukemia. Three primary chromosomal breakpoints were recurrently involved: 14q32, 16q22, and 22q11. Structural rearrangements of chromosome I were the most frequent (26% of the abnormal cases), but always as a secondary change. Rearrangements of band 14q32 were found in 22% of the abnormal cases. Among the multiple myeloma patients who showed an abnormal karyotype, 33 (46%) were hyperdiploid, most frequently with 52–56 chromosomes, 29 patients (40%) were pseudodiploid, and the remaining 12 cases (14%) were hypodiploid. A highly significant relation was observed between the presence of an abnormal karyotype and the following clinical parameters: stage III (P = 0.0001), bone marrow plasma cell infiltration greater than 30% (P = 0.0001), presence of bone lesions (P = 0.0009), and β2‐microglobulin levels greater than 4 mg/L (P = 0.0001). Genes Chromosom. Cancer 18:84–93, 1997. © 1997 Wiley‐Liss, Inc.

Transcatheter mitral valve implantation using balloon-expandable valves in selected patients with bioprosthesis or annuloplasty failure or severe MAC was associated with a low rate of peri-procedural complications and acceptable long-term outcomes.

Transcatheter mitral valve replacement (TMVR) using balloon-expandable valves has become an alternative therapy for selected patients with mitral valve disease. Up to now, the transapical approach has been the preferred route, but the transseptal approach is becoming increasingly popular due to its reduced invasiveness and increased safety. However, transseptal TMVR procedures are technically challenging, and little is known about the screening process required before this therapy. The authors provide operators with a step-by-step approach from the screening process to follow-up care for transseptal TMVR procedures.

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