Hormad1 mutation disrupts synaptonemal complex formation, recombination, and chromosome segregation in mammalian meiosis

Meiosis is unique to germ cells and essential for reproduction. During the first meiotic division, homologous chromosomes pair, recombine, and form chiasmata. The homologues connect via axial elements and numerous transverse filaments to form the synaptonemal complex. The synaptonemal complex is a critical component for chromosome pairing, segregation, and recombination. We previously identified a novel germ cell-specific HORMA domain encoding gene, Hormad1, a member of the synaptonemal complex and a mammalian counterpart to the yeast meiotic HORMA domain protein Hop1. Hormad1 is essential for mammalian gametogenesis as knockout male and female mice are infertile. Hormad1 deficient (Hormad1-/-) testes exhibit meiotic arrest in the early pachytene stage, and synaptonemal complexes cannot be visualized by electron microscopy. Hormad1 deficiency does not affect localization of other synaptonemal complex proteins, SYCP2 and SYCP3, but disrupts homologous chromosome pairing. Double stranded break formation and early recombination events are disrupted in Hormad1-/- testes and ovaries as shown by the drastic decrease in the γH2AX, DMC1, RAD51, and RPA foci. HORMAD1 co-localizes with cH2AX to the sex body during pachytene. BRCA1, ATR, and γH2AX co-localize to the sex body and participate in meiotic sex chromosome inactivation and transcriptional silencing. Hormad1 deficiency abolishes γH2AX, ATR, and BRCA1 localization to the sex chromosomes and causes transcriptional de-repression on the X chromosome. Unlike testes, Hormad1-/- ovaries have seemingly normal ovarian folliculogenesis after puberty. However, embryos generated from Hormad1-/- oocytes are hyper- and hypodiploid at the 2 cell and 8 cell stage, and they arrest at the blastocyst stage. HORMAD1 is therefore a critical component of the synaptonemal complex that affects synapsis, recombination, and meiotic sex chromosome inactivation and transcriptional silencing. © 2010 Shin et al

Peculiarities of polyneuropathy in the peripheral t-cell lymphoma with cytostatics

This paper presents data on the occurrence and form of polyneuropathy in the peripheral T-cell lymphoma, and its main pathogenesis elements. Here the toxic effects of cytotoxic drugs and their role in the impairment of the nervous system have been describe

Exocyst-mediated membrane trafficking of the lissencephaly-associated ECM receptor dystroglycan is required for proper brain compartmentalization

To assemble a brain, differentiating neurons must make proper connections and establish specialized brain compartments. Abnormal levels of cell adhesion molecules disrupt these processes. Dystroglycan (Dg) is a major non-integrin cell adhesion receptor, deregulation of which is associated with dramatic neuroanatomical defects such as lissencephaly type II or cobblestone brain. The previously established Drosophila model for cobblestone lissencephaly was used to understand how Dg is regulated in the brain. During development, Dg has a spatiotemporally dynamic expression pattern, fine-tuning of which is crucial for accurate brain assembly. In addition, mass spectrometry analyses identified numerous components associated with Dg in neurons, including several proteins of the exocyst complex. Data show that exocyst-based membrane trafficking of Dg allows its distinct expression pattern, essential for proper brain morphogenesis. Further studies of the Dg neuronal interactome will allow identification of new factors involved in the development of dystroglycanopathies and advance disease diagnostics in humans

Algal and cyanobacterial diversity in saline rivers of the Elton Lake Basin (Russia) studied via light microscopy and next-generation sequencing

Naturally saline rivers are known in various regions of the world. Saline rivers with a salinity gradient from the source to the mouth are particularly interesting, because the range of salinity is the structure-forming factor of the hydrobiont assemblage. Such rivers are represented by saline rivers of the Elton Lake Basin in Volgograd region of Russia (the Bolshaya Samoroda River and the Malaya Samoroda River). Herein, we analyzed taxonomic structure and species diversity of microalgae and Cyanobacteria of the saline rivers flowing into the Elton Lake by light microscopy and next-generation sequencing. The differences and possible causes of inconsistencies in the results obtained by these methods are discussed. In total, 91 taxa of microorganisms were identified by integrated approach in the assemblages of microalgae and Cyanobacteria in the middle course of the Bolshaya Samoroda River, and 60 taxa – in the river mouth. The species diversity of those assemblages in the hypersaline Malaya Samoroda River was lower: 27 taxa from the middle course and 23 taxa from the mouth. Next-generation sequencing allowed us to refine and expand the list of microalgae taxa in the studied saline rivers due to detection of species which were hard to identify, low-abundance taxa, as well as extremely small-cell forms. Some discrepancies between the data obtained by light microscopy and next-generation sequencing indicate the advantage of simultaneous use of both methods for study of the algae communities. Such a comprehensive approach provides the most accurate and correct list of taxa added with the morphological descriptions and 18S rRNA and 16S rRNA partial sequences. Generally, 18 taxa have been recorded for the first time in the Bolshaya Samoroda River, belonging to the phyla Chlorophyta (Borodinellopsis sp., Chlorochytrium lemnae Cohn, Caespitella sp., Halochlorococcum sp., Tetraselmis cordiformis (H. J. Carter) F. Stein), Ochrophyta (Pseudocharaciopsis ovalis (Chodat) D. J. Hibberd, Characiopsis sp., Poterioochromonas stipitata Scherffel, Chrysolepidomonas sp.), Euglenozoa (Euglena bucharica I. Kisselev, Lepocinclis tripteris (Dujardin) B. Marin & Melkonian, Phacus orbicularis K. Hübner, P. parvulus G. A. Klebs), Cryptophyta (Hemiselmis cryptochromatica C. E. Lane & J. M. Archibald, Rhodomonas sp., Hanusia phi J. A. Deane), Haptophyta (Pavlova sp.), Cyanobacteria (Johanseninema constrictum (Szafer) Hasler, Dvorák & Poulícková). Seven taxa have been detected for the first time in the algal and cyanobacterial assemblages of the Malaya Samoroda River from the phyla Chlorophyta (Tetraselmis cordiformis, T. arnoldii (Proschkina-Lavrenko) R. E. Norris, Hori & Chihara, T. tetrathele (West) Butcher, Pyrobotrys elongatus Korshikov), Cryptophyta (Hanusia phi), and Cyanobacteria (Synechococcus elongatus (Nägeli) Nägeli, Oscillatoria simplicissima Gomont)

Modes and the alpha-gamma transition in rf capacitive discharges in N2O at different rf frequencies

This paper reports current-voltage characteristics and pressure-voltage transition curves from the weak-current a-mode to the strong-current g-mode for rf capacitive discharges in N2O at frequencies of 2 MHz, 13.56 MHz, and 27.12 MHz. At 2 MHz the rf discharge is mostly resistive whereas at 13.56 MHz and 27.12 MHz it is mostly capacitive. The weak-current a-mode was found to exist only above a certain minimum gas pressure for all frequencies studied [N. Yatsenko Sov. Phys. Tech. Phys. 26, 678 (19810] previously proposed that the a−g transition corresponds to breakdown of the sheaths. However, we show that this is the case only for sufficiently high gas pressures. At lower pressure there is a smooth transition from the weak-current a-mode to a strong-current g-mode, in which the sheaths produce fast electrons but the sheath has not undergone breakdown

Profiling of the muscle-specific dystroglycan interactome reveals the role of Hippo signaling in muscular dystrophy and age-dependent muscle atrophy.

Dystroglycanopathies are a group of inherited disorders characterized by vast clinical and genetic heterogeneity and caused by abnormal functioning of the ECM receptor dystroglycan (Dg). Remarkably, among many cases of diagnosed dystroglycanopathies, only a small fraction can be linked directly to mutations in Dg or its regulatory enzymes, implying the involvement of other, not-yet-characterized, Dg-regulating factors. To advance disease diagnostics and develop new treatment strategies, new approaches to find dystroglycanopathy-related factors should be considered. The Dg complex is highly evolutionarily conserved; therefore, model genetic organisms provide excellent systems to address this challenge. In particular, Drosophila is amenable to experiments not feasible in any other system, allowing original insights about the functional interactors of the Dg complex. METHODS: To identify new players contributing to dystroglycanopathies, we used Drosophila as a genetic muscular dystrophy model. Using mass spectrometry, we searched for muscle-specific Dg interactors. Next, in silico analyses allowed us to determine their association with diseases and pathological conditions in humans. Using immunohistochemical, biochemical, and genetic interaction approaches followed by the detailed analysis of the muscle tissue architecture, we verified Dg interaction with some of the discovered factors. Analyses of mouse muscles and myocytes were used to test if interactions are conserved in vertebrates. RESULTS: The muscle-specific Dg complexome revealed novel components that influence the efficiency of Dg function in the muscles. We identified the closest human homologs for Dg-interacting partners, determined their significant enrichment in disease-associations, and verified some of the newly identified Dg interactions. We found that Dg associates with two components of the mechanosignaling Hippo pathway: the WW domain-containing proteins Kibra and Yorkie. Importantly, this conserved interaction manages adult muscle size and integrity. CONCLUSIONS: The results presented in this study provide a new list of muscle-specific Dg interactors, further analysis of which could aid not only in the diagnosis of muscular dystrophies, but also in the development of new therapeutics. To regulate muscle fitness during aging and disease, Dg associates with Kibra and Yorkie and acts as a transmembrane Hippo signaling receptor that transmits extracellular information to intracellular signaling cascades, regulating muscle gene expression

Halotolerant strain of Chlorococcum oleofaciens from the Lake Elton Biosphere Reserve

Chlorococcum oleofaciens is one of the most studied representatives of the Chlorococcum genus, both on the ultrastructural and molecular levels. This alga is very interesting due to its ability to hypersynthetize saturated and unsaturated fatty acids and the possibility of using it as a promising object for biofuel production. This research is devoted to the study of the halotolerant strain of Ch. oleofaciens Ch-1 extracted from the water of the Khara River (Lake Elton Biosphere Reserve, Russia, a UNESCO World Heritage site), mineralization of 14‰. The strain Ch. oleofaciens Ch-1 was studied at the morphological level (light microscopy), as well as using molecular genetics methods (18S rDNA). The objectives of the study included establishing the range of halotolerance of the allocated strain of Ch. oleofaciens as a whole, revealing borders of level of mineralization that are optimum for algae growth, and also tracing features of its morphology and cycle of development in the conditions of various salinity. In the course of the studies performed it was established that the extracted strain of Ch. oleofaciens Ch-1 differed from the typical one by greater variability of some morphological features and had a wide ecological valence: the range of its halotolerance was 0–60‰. The maximum values of quantitative development of Ch. oleofaciens Ch-1 were registered at mineralization of 0–14‰. It is shown that with increasing salinity in the development cycle of the strain, the duration of the adaptation phase increases, the exponential phase decreases, small celled forms are replaced by large celled forms and reproduction features are noted. The obtained results can be used for selection of optimal conditions for cultivation of the halotolerant strain of Ch. oleofaciens for biotechnological purposes

DataJoint: managing big scientific data using MATLAB or Python

The rise of big data in modern research poses serious challenges for data management: Large and intricate datasets from diverse instrumentation must be precisely aligned, annotated, and processed in a variety of ways to extract new insights. While high levels of data integrity are expected, research teams have diverse backgrounds, are geographically dispersed, and rarely possess a primary interest in data science. Here we describe DataJoint, an open-source toolbox designed for manipulating and processing scientific data under the relational data model. Designed for scientists who need a flexible and expressive database language with few basic concepts and operations, DataJoint facilitates multi-user access, efficient queries, and distributed computing. With implementations in both MATLAB and Python, DataJoint is not limited to particular file formats, acquisition systems, or data modalities and can be quickly adapted to new experimental designs. DataJoint and related resources are available at http://datajoint.github.com

Understanding the notion "mariagge" in british lingvoculture (by means of its verbalization)

The article deals with the studying the structure of the subconcept "marriage" in modern british lingvoculture. The subconcept is viewed as one of the basic conceptual structural elements of the concepts sphere "family relations

Performance of a 229 Thorium solid-state nuclear clock

The 7.8 eV nuclear isomer transition in 229 Thorium has been suggested as an etalon transition in a new type of optical frequency standard. Here we discuss the construction of a "solid-state nuclear clock" from Thorium nuclei implanted into single crystals transparent in the vacuum ultraviolet range. We investigate crystal-induced line shifts and broadening effects for the specific system of Calcium fluoride. At liquid Nitrogen temperatures, the clock performance will be limited by decoherence due to magnetic coupling of the Thorium nucleus to neighboring nuclear moments, ruling out the commonly used Rabi or Ramsey interrogation schemes. We propose a clock stabilization based on counting of flourescence photons and present optimized operation parameters. Taking advantage of the high number of quantum oscillators under continuous interrogation, a fractional instability level of 10^{-19} might be reached within the solid-state approach.Comment: 28 pages, 9 figure