Structure of UBE2K–Ub/E3/polyUb reveals mechanisms of K48-linked Ub chain extension

Ubiquitin (Ub) chain types govern distinct biological processes. K48-linked polyUb chains target substrates for proteasomal degradation, but the mechanism of Ub chain synthesis remains elusive due to the transient nature of Ub handover. Here, we present the structure of a chemically trapped complex of the E2 UBE2K covalently linked to donor Ub and acceptor K48-linked di-Ub, primed for K48-linked Ub chain synthesis by a RING E3. The structure reveals the basis for acceptor Ub recognition by UBE2K active site residues and the C-terminal Ub-associated (UBA) domain, to impart K48-linked Ub specificity and catalysis. Furthermore, the structure unveils multiple Ub-binding surfaces on the UBA domain that allow distinct binding modes for K48- and K63-linked Ub chains. This multivalent Ub-binding feature serves to recruit UBE2K to ubiquitinated substrates to overcome weak acceptor Ub affinity and thereby promote chain elongation. These findings elucidate the mechanism of processive K48-linked polyUb chain formation by UBE2K.

Novel poly(arylene ether nitrile) containing pendant aliphtatic ring in the chain: Synthesis and properties

Two kinds of novel poly(arylene ether nitrile)s (CPDP-DCBN and CHDP-DCBN) containing pendant aliphtatic ring were synthesized by 4,4′-cyclopentane-1,1′-diyldiphenol (CPDP) or 4,4′-cyclohexane-1,1′-diyldiphenol (CHDP) and 2,6-dichlorobenzonitrile (DCBN) in this work. The inherent viscosities of poly(arylene ether nitrile)s (PENs) were in the range of 0.701–0.806 dL g−1. The polymers showed high glass transition temperatures ( T g) of 185.4–196.4°C and weight-loss temperatures ( T5%) of 447.8–454.3°C. The obtained CPDP-DCBN and CHDP-DCBN could be hot pressed into the films, which showed the tensile strengths of 82.6 MPa and 86.8 MPa, respectively. And the storage modulus of CPDP-DCBN and CHDP-DCBN were about 1.0 GPa and 1.5 GPa at 150°C, respectively. Additionally, the PENs could be dissolved in many solutions at room temperature, such as NMP and concentrated H2SO4, indicating that they had good solubility; they can be processed by the solution method. Meanwhile, the optical transmittance of CPDP-DCBN was 78.1% at 450 nm; it has potential to be applied to the heat-resistant optical film.

A review of the ecology, genetics, evolution, and magnetosome –induced behaviours of the magnetotactic bacteria

The discovery of magnetosome and magnetotaxis in its most simple form in the magnetotactic bacteria (MTB) had created the tremendous impetus. MTB, spanning multiple phyla, are distributed worldwide, and they form the organelles called magnetosomes for biomineralization. Eight phylotypes of MTB belong to Alphaproteobacteria and Nitrospirae. MTB show preference for specific redox and oxygen concentration. Magnetosome chains function as the internal compass needle and align the bacterial cells passively along the local geomagnetic field (GMF). The nature of magnetosomes produced by MTB and their phylogeny suggest that bullet-shaped magnetites appeared about 3.2 billion years ago with the first magnetosomes. All MTB contains ten genes in conserved mamAB operon for magnetosome chain synthesis of which nine genes are conserved in greigite-producing MTB. Many candidate genes identify the aero-, redox-, and perhaps phototaxis. Among the prokaryotes, the MTB possess the highest number of O2-binding proteins. Magnetofossils serve as an indicator of oxygen and redox levels of the ancient environments. Most descendants of ancestral MTB lost the magnetosome genes in the course of evolution. Environmental conditions initially favored the evolution of MTB and expansion of magnetosome-formation genes. Subsequent changes in atmospheric oxygen concentration have led to changes in the ecology of MTB, loss of magnetosome genes, and evolution of nonMTB.

Functional-target management models of regional security (Part 2. Covering and adequate systems)

Работа направлена на развитие формального аппарата анализа и синтеза многоуровневых распределенных систем управления региональной безопасностью с целью повышения адекватности этих систем в условиях усложнения управленческих задач в этой области. В работе предложены математические модели управления региональной безопасностью , основанные на функционально-целевой технологии и теории иерархических многоуровневых систем. Модели обеспечивают формальную постановку задач и практическую реализацию процедур автоматизации структурно-алгоритмического синтеза адекватных систем информационной поддержки управленческой деятельности. Работа состоит из двух частей. В первой части рассматриваются формальные процедуры синтеза цепочек целей и действий в управлении региональной безопасностью. Во второй части обсуждаются вопросы синтеза моделей покрывающих и адекватных систем, обеспечивающих решение задач управления путем удовлетворения условий изоморфизма всех уровней их декомпозиции и функциональной организации системы. The study is aimed to development of the mathematical apparatus for analysis and synthesis of the multi-level distributed management systems of regional security for the purpose of system adequacy enhancement under management problems complication in this field. Mathematical models for regional security management based on the functional-target technology and the theory of hierarchical multi-level systems are proposed. Models provide formalized problem statement and practical implementation of automation procedures of the structural-algorithmic synthesis of appropriate systems for information support of management activity. Our research work consists of two parts. In the first part formal procedures of the chain synthesis of goals and actions in regional security management are considered. In the second part the model synthesis issues of covering and adequate systems, providing management problem-solving by isomorphism conditions settlement of the all problem decomposition levels and the system functional organization.

Pathomechanisms of Immunological Disturbances in β-Thalassemia

Thalassemia, a chronic disease with chronic anemia, is caused by mutations in the β-globin gene, leading to reduced levels or complete deficiency of β-globin chain synthesis. Patients with β-thalassemia display variable clinical severity which ranges from asymptomatic features to severe transfusion-dependent anemia and complications in multiple organs. They not only are at increased risk of blood-borne infections resulting from multiple transfusions, but they also show enhanced susceptibility to infections as a consequence of coexistent immune deficiency. Enhanced susceptibility to infections in β-thalassemia patients is associated with the interplay of several complex biological processes. β-thalassemia-related abnormalities of the innate immune system include decreased levels of complement, properdin, and lysozyme, reduced absorption and phagocytic ability of polymorphonuclear neutrophils, disturbed chemotaxis, and altered intracellular metabolism processes. According to available literature data, immunological abnormalities observed in patients with thalassemia can be caused by both the disease itself as well as therapies. The most important factors promoting such alterations involve iron overload, phenotypical and functional abnormalities of immune system cells resulting from chronic inflammation oxidative stress, multiple blood transfusion, iron chelation therapy, and splenectomy. Unravelling the mechanisms underlying immune deficiency in β-thalassemia patients may enable the designing of appropriate therapies for this group of patients.

Cytoplasmic factories for axonemal dynein assembly

ABSTRACT Axonemal dyneins power the beating of motile cilia and flagella. These massive multimeric motor complexes are assembled in the cytoplasm, and subsequently trafficked to cilia and incorporated into the axonemal superstructure. Numerous cytoplasmic factors are required for the dynein assembly process, and, in mammals, defects lead to primary ciliary dyskinesia, which results in infertility, bronchial problems and failure to set up the left-right body axis correctly. Liquid–liquid phase separation (LLPS) has been proposed to underlie the formation of numerous membrane-less intracellular assemblies or condensates. In multiciliated cells, cytoplasmic assembly of axonemal dyneins also occurs in condensates that exhibit liquid-like properties, including fusion, fission and rapid exchange of components both within condensates and with bulk cytoplasm. However, a recent extensive meta-analysis suggests that the general methods used to define LLPS systems in vivo may not readily distinguish LLPS from other mechanisms. Here, I consider the time and length scales of axonemal dynein heavy chain synthesis, and the possibility that during translation of dynein heavy chain mRNAs, polysomes are crosslinked via partially assembled proteins. I propose that axonemal dynein factory formation in the cytoplasm may be a direct consequence of the sheer scale and complexity of the assembly process itself.

Report of two siblings with spondylodysplastic Ehlers-Danlos syndrome and B4GALT7 deficiency

Background The spondylodysplastic Ehlers-Danlos subtype (OMIM #130070) is a rare connective tissue disorder characterized by a combination of connective tissue symptoms, skeletal features and short stature. It is caused by variants in genes encoding for enzymes involved in the proteoglycan biosynthesis or for a zinc transporter. Presentation of cases We report two brothers with a similar phenotype of short stature, joint hypermobility, distinct craniofacial features, developmental delay and severe hypermetropia indicative for a spondylodysplastic Ehlers-Danlos subtype. One also suffered from a recurrent pneumothorax. Gene panel analysis identified two compound heterozygous variants in the B4GALT7 gene: c.641G > A and c.723 + 4A > G. B4GALT7 encodes for galactosyltransferase I, which is required for the initiation of glycosaminoglycan side chain synthesis of proteoglycans. Conclusions This is a first full report on two cases with spondylodysplastic Ehlers-Danlos syndrome and the c.723 + 4A > G variant of B4GALT7. The recurrent pneumothoraces observed in one case expand the variable phenotype of the syndrome.