Dimerization of FIR upon FUSE DNA binding suggests a mechanism of c-myc inhibition

c-myc is essential for cell homeostasis and growth but lethal if improperly regulated. Transcription of this oncogene is governed by the counterbalancing forces of two proteins on TFIIH—the FUSE binding protein (FBP) and the FBP-interacting repressor (FIR). FBP and FIR recognize single-stranded DNA upstream of the P1 promoter, known as FUSE, and influence transcription by oppositely regulating TFIIH at the promoter site. Size exclusion chromatography coupled with light scattering reveals that an FIR dimer binds one molecule of single-stranded DNA. The crystal structure confirms that FIR binds FUSE as a dimer, and only the N-terminal RRM domain participates in nucleic acid recognition. Site-directed mutations of conserved residues in the first RRM domain reduce FIR's affinity for FUSE, while analogous mutations in the second RRM domain either destabilize the protein or have no effect on DNA binding. Oppositely oriented DNA on parallel binding sites of the FIR dimer results in spooling of a single strand of bound DNA, and suggests a mechanism for c-myc transcriptional control

TO THE QUESTION OF CLASSIFICATION AND TREATMENT TACTICS OF HYPERSPLENISM PORTAL GENESIS IN CHILDREN

The paper presents the experience in the treatment of 128 children with the syndrome of portal hypertension (SPH) from 1997 to 2013. Hypersplenism (HS) was diagnosed in 48 children (37,5%). Applied methods of medical and surgical treatment of HS. The authors of the HS divides into three forms clinical course: 1) compensated, 2) subcompensated and 3) decompensated. Compensated form of HS diagnosed in 19-and children (14,8%) and given medical treatment. Subcompensated form detected in 19 patients (14,8%) and requires both medical and surgical treatment. Decompensated form HS exhibited 10 patients (7,8%) was cured surgical method

CORRECTION DYSBACTERIOSIS IN REHABILITATION PROGRAMS FOR CHILDREN UNDERGOING SURGERY ON THE COLON AND ANORECTAL ZONE

Rehabilitation of children undergoing surgery for colon and rectum is an important issue of pediatric surgery. Its relevance is due to the widespread development of these anomalies requiring surgical correction –  1:4000–5000 newborns. In all patients with this disease is marked by inflammatory changes in the intestinal mucosa. Use of      73  antibacterial drugs in the pre-and postoperative periods in 100% of cases, causes the development of  intestinal dysbiosis.Dysbiosis uniqueness is manifested in the fact that this disease is in the interests of doctors of different specialties. Traditional methods for correcting violations mikrobiotsinoz gut is not always sufficiently effective in surgical patients. The purpose of this study to optimize the treatment and prevention circuit dysbacteriosis in surgical patients

Immunohistochemical Biomarkers of Gastrointestinal, Pancreatic, Pulmonary, and Thymic Neuroendocrine Neoplasms

Neuroendocrine neoplasms (NENs) are a heterogeneous group of epithelial neoplastic proliferations that irrespective of their primary site share features of neural and endocrine differentiation including the presence of secretory granules, synaptic-like vesicles, and the ability to produce amine and/or peptide hormones. NENs encompass a wide spectrum of neoplasms ranging from well-differentiated indolent tumors to highly aggressive poorly differentiated neuroendocrine carcinomas. Most cases arise in the digestive system and in thoracic organs, i.e., the lung and thymus. A correct diagnostic approach is crucial for the management of patients with both digestive and thoracic NENs, because their high clinical and biological heterogeneity is related to their prognosis and response to therapy. In this context, immunohistochemistry represents an indispensable diagnostic tool that pathologists need to use for the correct diagnosis and classification of such neoplasms. In addition, immunohistochemistry is also useful in identifying prognostic and theranostic markers. In the present article, the authors will review the role of immunohistochemistry in the routine workup of digestive and thoracic NENs