Амидофосфитный реагент и твердофазный носитель для синтеза 5'- и З'-фосфорилированных олигонуклеотидов

Syntheses of a phosphoramidite reagent for 5'-phosphorylation of oligonucleotides, and of a modified solid-phase support (controlled pore glass, CPG) for 3'-phosphate modification of oligonucleotides are described. Efficasy of the reagents has been confirmed by the synthesis of phosphorylated oligonucleotides. The oligonucleotides have been analyzed by electrophoresis and HPLC.Описан синтез амидофосфитного реагента для получения олигонуклеотидов, модифицированных по 5 '-положению остатком фосфорной кислоты, а также синтез твердофазного носителя (стекла с контролируемым размером пор, CPG), предназначенного для получения 3'-фосфорилированных олигонуклеотидов. Эффективность реагентов подтверждена синтезом фосфорилированных олигонуклеотидов, которые проанализированы с помощью электрофореза и ВЭЖХ

ОСОБЕННОСТИ СВЯЗЫВАНИ Я БИС -(3′,5′)-ЦИКЛИЧЕСКОГО ДИМЕРНОГО ГУАНОЗИНМОНОФОСФАТА С ТЕТРАМЕРАМИ ГЕМОГЛОБИНА ЧЕЛОВЕКА

Molecular modeling complexes of bis-(3′, 5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) with human oxyhemoglobin HbA1 and the analysis of the cyclic diguanylic acid inhibitory effect on the binding of 1,8-ANS to HbA1 carried out by the steady-state fluorescence spectroscopy showed that the most specific binding site of c-di-GMP in hemoglobin oligomers is the central regulatory region of this protein (competitive inhibition constant is 2.91 ± 0.54·10−5 М). At high concentrations of 1,8-ANS c-di-GMP inhibitory effect on the probe binding is non-competitive (non-competitive inhibition constant is 0.79 ± 0.11·10−4 М), indicating the ability of c-di-GMP interact with less specific surface areas of human oxyhemoglobin.Молекулярные модели комплексов бис-(3′,5′)-циклического димерного гуанозинмонофосфата (c-di-GMP) с гемоглобином человека в R-состоянии показали, что c-di-GMP связывается с тетрамерами гемоглобина со стороны b-входа в центральную полость гемопротеида в DPG-связующем сайте белка.Анализ ингибирующего действия дигуанилата на связывание 1,8-ANS с тетрамерами гемопротеида, выполненный методом стационарной флуоресцентной спектроскопии, показал, что наиболее специфическим сайтом связывания c-di-GMP в олигомерах данного белка является его центральная регуляторная область (константа конкурентного ингибирования 2,91 ± 0,54·10−5 М). При высоких концентрациях 1,8-ANS ингибирующее действие циклического дигуанилата на связывание зонда становится неконкурентным (константа для неконкурентного ингибирования 0,79 ± 0,11·10−4 М), указывая на способность c-di-GMP взаимодействовать и с менее специфическими поверхностными участками оксигемоглобина человека

Standards of Care for the Health of Transgender and Gender Diverse People, Version 8

Background: Transgender healthcare is a rapidly evolving interdisciplinary field. In the last decade, there has been an unprecedented increase in the number and visibility of transgender and gender diverse (TGD) people seeking support and gender-affirming medical treatment in parallel with a significant rise in the scientific literature in this area. The World Professional Association for Transgender Health (WPATH) is an international, multidisciplinary, professional association whose mission is to promote evidence-based care, education, research, public policy, and respect in transgender health. One of the main functions of WPATH is to promote the highest standards of health care for TGD people through the Standards of Care (SOC). The SOC was initially developed in 1979 and the last version (SOC-7) was published in 2012. In view of the increasing scientific evidence, WPATH commissioned a new version of the Standards of Care, the SOC-8. Aim: The overall goal of SOC-8 is to provide health care professionals (HCPs) with clinical guidance to assist TGD people in accessing safe and effective pathways to achieving lasting personal comfort with their gendered selves with the aim of optimizing their overall physical health, psychological well-being, and self-fulfillment. Methods: The SOC-8 is based on the best available science and expert professional consensus in transgender health. International professionals and stakeholders were selected to serve on the SOC-8 committee. Recommendation statements were developed based on data derived from independent systematic literature reviews, where available, background reviews and expert opinions. Grading of recommendations was based on the available evidence supporting interventions, a discussion of risks and harms, as well as the feasibility and acceptability within different contexts and country settings. Results: A total of 18 chapters were developed as part of the SOC-8. They contain recommendations for health care professionals who provide care and treatment for TGD people. Each of the recommendations is followed by explanatory text with relevant references. General areas related to transgender health are covered in the chapters Terminology, Global Applicability, Population Estimates, and Education. The chapters developed for the diverse population of TGD people include Assessment of Adults, Adolescents, Children, Nonbinary, Eunuchs, and Intersex Individuals, and people living in Institutional Environments. Finally, the chapters related to gender-affirming treatment are Hormone Therapy, Surgery and Postoperative Care, Voice and Communication, Primary Care, Reproductive Health, Sexual Health, and Mental Health. Conclusions: The SOC-8 guidelines are intended to be flexible to meet the diverse health care needs of TGD people globally. While adaptable, they offer standards for promoting optimal health care and guidance for the treatment of people experiencing gender incongruence. As in all previous versions of the SOC, the criteria set forth in this document for gender-affirming medical interventions are clinical guidelines; individual health care professionals and programs may modify these in consultation with the TGD person