Straightforward synthesis of 1-alkyl-2-(trifluoromethyl)aziridines starting from 1,1,1-trifluoroacetone

An efficient and straightforward approach towards the synthesis of 1-alkyl-2-(trifluoromethyl)aziridines starting from 1,1,1-trifluoroacetone via imination, alpha-chlorination, hydride reduction and ring closure was developed. In addition, novel primary beta-iodo amines were obtained by regioselective ring opening of these 2-(trifluoromethyl)aziridines using alkyl iodides, and their synthetic potential was demonstrated by converting them into novel alpha-CF(3)-beta-phenylethylamines upon treatment with lithium diphenylcuprate

Ancestral glycoprotein hormone-receptor pathway controls growth in C. elegans

In vertebrates, thyrostimulin is a highly conserved glycoprotein hormone that, besides thyroid stimulating hormone (TSH), is a potent ligand of the TSH receptor. Thyrostimulin is considered the most ancestral glycoprotein hormone and orthologs of its subunits, GPA2 and GPB5, are widely conserved across vertebrate and invertebrate animals. Unlike TSH, however, the functions of the thyrostimulin neuroendocrine system remain largely unexplored. Here, we identify a functional thyrostimulin-like signaling system in Caenorhabditis elegans. We show that orthologs of GPA2 and GPB5, together with thyrotropin-releasing hormone (TRH) related neuropeptides, constitute a neuroendocrine pathway that promotes growth in C. elegans. GPA2/GPB5 signaling is required for normal body size and acts through activation of the glycoprotein hormone receptor ortholog FSHR-1. C. elegans GPA2 and GPB5 increase cAMP signaling by FSHR-1 in vitro. Both subunits are expressed in enteric neurons and promote growth by signaling to their receptor in glial cells and the intestine. Impaired GPA2/GPB5 signaling causes bloating of the intestinal lumen. In addition, mutants lacking thyrostimulin-like signaling show an increased defecation cycle period. Our study suggests that the thyrostimulin GPA2/GPB5 pathway is an ancient enteric neuroendocrine system that regulates intestinal function in ecdysozoans, and may ancestrally have been involved in the control of organismal growth

Сенсибилизация к аллергенам клещей домашней пыли у детей

ДЫХАТЕЛЬНАЯ ГИПЕРЧУВСТВИТЕЛЬНОСТЬАЛЛЕРГОЗЫ РЕСПИРАТОРНЫЕГИПЕРСЕНСИБИЛИЗАЦИЯ РЕСПИРАТОРНАЯРЕСПИРАТОРНАЯ АЛЛЕРГИЯАЛЛЕРГЕНЫКЛЕЩИ ПЫЛЕВЫЕ ДОМАШНИЕDERMATOPHAGOIDES PTERONYSSINUSDERMATOPHAGOIDES FARINAEСЕНСИБИЛИЗАЦИЯ БИОЛОГИЧЕСКАЯСЕНСИБИЛИЗАЦИЯ К АЛЛЕРГЕНАМДЕТИОБЗОР ЛИТЕРАТУРЫАллергические заболевания представляют серьезную проблему современной медицины. Сенсибилизация к ингаляционным аллергенам является одним из ключевых факторов формирования респираторных аллергозов. Среди аэроаллергенов важное значение играют аллергенные компоненты домашней пыли – клещи Dermatophagoides pteronyssinus и Dermatophagoides farinae, составляющие до 90% акарофауны жилых помещений. В формировании сенсибилизации к клещам домашней пыли также предполагается роль индивидуальных источников аллергенов. Сенсибилизация к мажорным компонентам аллергена клещей домашней пыли ассоциируется с риском развития бронхиальной астмы, к минорным (Der p 10) – риском развития перекрестных реакций с тропомиозином других беспозвоночных, тропомиозином человека. Аллергены клещей домашней пыли (Der p 2 и Der f 2) могут быть ответственны за симптомы оральной клещевой анафилаксии, а также способствовать развитию сенсибилизации к бактериальным антигенам Staphylococcus aureus и Escherichia coli. В 1 части статьи изложены биология и источники клеща домашней пыли. Представлена классификация аллергенов, пути сенсибилизации и распространенность сенсибилизации к клещу домашней пыли у детей.Allergic diseases are a serious problem in modern medicine. Sensitization to inhalation allergens is one of the key factors in the formation of respiratory allergoses. Among aeroallergens, allergenic components of domestic dust play an important role – mites Dermatophagoides pteronyssinus and Dermatophagoides farinae, that make up to 90% of the acarofauna of residential premises. In the formation of sensitization to domestic dust mites, the role of individual sources of allergens is also considered. Sensitization to the major components of the domestic dust mite allergens is associated with the risk of developing bronchial asthma, to minor ones (Der p 10) – the risk of cross-reactions with tropomyosin of other invertebrates, human tropomyosin. Domestic dust mite allergens (Der p 2 and Der f 2) may be responsible for the symptoms of oral tick-born anaphylaxis as well as for the development of sensitization to bacterial antigens of Staphylococcus aureus and Escherichia coli. Part 1 of this article outlines biology and sources of the domestic dust mite. The classification of allergens, sensitization pathways and the prevalence of sensitization to domestic dust mite in children are presented

Clustering schizophrenia genes by their temporal expression patterns aids functional interpretation

Background Schizophrenia is a highly heritable brain disorder with a typical symptom onset in early adulthood. The 2-hit hypothesis posits that schizophrenia results from differential early neurodevelopment, predisposing an individual, followed by a disruption of later brain maturational processes that trigger the onset of symptoms. Study design We applied hierarchical clustering to transcription levels of 345 genes previously linked to schizophrenia, derived from cortical tissue samples from 56 donors across the lifespan. We subsequently calculated clustered-specific polygenic risk scores for 743 individuals with schizophrenia and 743 sex- and age-matched healthy controls. Study results Clustering revealed a set of 183 genes that was significantly upregulated prenatally and downregulated postnatally and 162 genes that showed the opposite pattern. The prenatally upregulated set of genes was functionally annotated to fundamental cell cycle processes, while the postnatally upregulated set was associated with the immune system and neuronal communication. We found an interaction between the 2 scores; higher prenatal polygenic risk showed a stronger association with schizophrenia diagnosis at higher levels of postnatal polygenic risk. Importantly, this finding was replicated in an independent clinical cohort of 3233 individuals. Conclusions We provide genetics-based evidence that schizophrenia is shaped by disruptions of separable biological processes acting at distinct phases of neurodevelopment. The modeling of genetic risk factors that moderate each other’s effect, informed by the timing of their expression, will aid in a better understanding of the development of schizophrenia

Selective synthesis of functionalized trifluoromethylated pyrrolidines, piperidines, and azepanes starting from 1-tosyl-2-(trifluoromethyl)aziridine

This paper reports on the generation and alkylation of the 1-tosyl-2-(trifluoromethyl)aziridin-2-yl anion with omega,omega'-dihaloalkanes, followed by a novel ring-expansion protocol toward 2-CF3-pyrrolidines, 2-CF3-piperidines, and 3-CF3-azepanes. A variety of halogen, oxygen, nitrogen, sulfur, and carbon nucleophiles was used to trigger this ring rearrangement, resulting in CF3-azaheterocycles bearing different types of functionalized side chains