molecular organization
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2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Erika Prašnikar ◽  
Tanja Kunej ◽  
Mario Gorenjak ◽  
Uroš Potočnik ◽  
Borut Kovačič ◽  
...  

Abstract Background Women with uterine adenomyosis seeking assisted reproduction have been associated with compromised endometrial receptivity to embryo implantation. To understand the mechanisms involved in this process, we aimed to compare endometrial transcriptome profiles during the window of implantation (WOI) between women with and without adenomyosis. Methods We obtained endometrial biopsies LH-timed to the WOI from women with sonographic features of adenomyosis (n=10) and controls (n=10). Isolated RNA samples were subjected to RNA sequencing (RNA-seq) by the Illumina NovaSeq 6000 platform and endometrial receptivity classification with a molecular tool for menstrual cycle phase dating (beREADY®, CCHT). The program language R and Bioconductor packages were applied to analyse RNA-seq data in the setting of the result of accurate endometrial dating. To suggest robust candidate pathways, the identified differentially expressed genes (DEGs) associated with the adenomyosis group in the receptive phase were further integrated with 151, 173 and 42 extracted genes from published studies that were related to endometrial receptivity in healthy uterus, endometriosis and adenomyosis, respectively. Enrichment analyses were performed using Cytoscape ClueGO and CluePedia apps. Results Out of 20 endometrial samples, 2 were dated to the early receptive phase, 13 to the receptive phase and 5 to the late receptive phase. Comparison of the transcriptomics data from all 20 samples provided 909 DEGs (p<0.05; nonsignificant after adjusted p value) in the adenomyosis group but only 4 enriched pathways (Bonferroni p value < 0.05). The analysis of 13 samples only dated to the receptive phase provided suggestive 382 DEGs (p<0.05; nonsignificant after adjusted p value) in the adenomyosis group, leading to 33 enriched pathways (Bonferroni p value < 0.05). These included pathways were already associated with endometrial biology, such as “Expression of interferon (IFN)-induced genes” and “Response to IFN-alpha”. Data integration revealed pathways indicating a unique effect of adenomyosis on endometrial molecular organization (e.g., “Expression of IFN-induced genes”) and its interference with endometrial receptivity establishment (e.g., “Extracellular matrix organization” and “Tumour necrosis factor production”). Conclusions Accurate endometrial dating and RNA-seq analysis resulted in the identification of altered response to IFN signalling as the most promising candidate of impaired uterine receptivity in adenomyosis.


2021 ◽  
Author(s):  
Hanieh Falahati ◽  
Yumei Wu ◽  
Vanessa Feuerer ◽  
Pietro De Camilli

The spine apparatus is a specialization of the neuronal ER in dendritic spines consisting of stacks of interconnected cisterns separated by a dense matrix. Synaptopodin, a specific actin binding protein of the spine apparatus, is essential for its formation, but the underlying mechanisms remain unknown. We show that synaptopodin, when expressed in fibroblasts, forms actin-rich structures with connections to the ER, and that an ER-tethered synaptopodin assembles into liquid condensates. We also identified protein neighbors of synaptopodin in spines by in vivo proximity biotinylation. We validated a small subset of such proteins and showed that they co-assemble with synaptopodin in living cells. One of them is Pdlim7, an actin binding protein not previously identified in spines, and we show its precise colocalization with synaptopodin. We suggest that the matrix of the spine apparatus has the property of a liquid protein condensate generated by a multiplicity of low affinity interactions.


Nanomaterials ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 93
Author(s):  
Edward T. Samulski ◽  
Denisse Reyes-Arango ◽  
Alexandros G. Vanakaras ◽  
Demetri J. Photinos

The nature of the nanoscale structural organization in modulated nematic phases formed by molecules having a nonlinear molecular architecture is a central issue in contemporary liquid crystal research. Nevertheless, the elucidation of the molecular organization is incomplete and poorly understood. One attempt to explain nanoscale phenomena merely “shrinks down” established macroscopic continuum elasticity modeling. That explanation initially (and mistakenly) identified the low temperature nematic phase (NX), first observed in symmetric mesogenic dimers of the CB-n-CB series with an odd number of methylene spacers (n), as a twist–bend nematic (NTB). We show that the NX is unrelated to any of the elastic deformations (bend, splay, twist) stipulated by the continuum elasticity theory of nematics. Results from molecular theory and computer simulations are used to illuminate the local symmetry and physical origins of the nanoscale modulations in the NX phase, a spontaneously chiral and locally polar nematic. We emphasize and contrast the differences between the NX and theoretically conceivable nematics exhibiting spontaneous modulations of the elastic modes by presenting a coherent formulation of one-dimensionally modulated nematics based on the Frank–Oseen elasticity theory. The conditions for the appearance of nematic phases presenting true elastic modulations of the twist–bend, splay–bend, etc., combinations are discussed and shown to clearly exclude identifications with the nanoscale-modulated nematics observed experimentally, e.g., the NX phase. The latter modulation derives from packing constraints associated with nonlinear molecules—a chiral, locally-polar structural organization indicative of a new type of nematic phase.


Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 206
Author(s):  
Mariia Nesterkina ◽  
Serhii Smola ◽  
Nataliya Rusakova ◽  
Iryna Kravchenko

Hydrazones based on mono- and bicyclic terpenoids (verbenone, menthone and carvone) have been investigated in vitro as potential biomembrane penetration enhancers. In this regard, liposomes composed of lecithin or cardiolipin as phospholipid phase components with incorporated fluorescence probes have been prepared using the thin-film ultrasonic dispersion method. The mean particle size of the obtained liposomes, established using laser diffraction, was found to be 583 ± 0.95 nm, allowing us to categorize them as multilamellar vesicles (MLVs) according to their morphology. Pursuant to fluorescence analysis, we may assume a reduction in microviscosity and, consequently, a decrease in the packing density of lecithin and cardiolipin lipids to be the major mechanism of action for terpenoid hydrazones 1–15. In order to determine the molecular organization of the lipid matrix, lipids were isolated from rat strata cornea (SCs) and their interaction with tested compounds was studied by means of Fourier transform infrared spectroscopy. FT-IR examination suggested that these hydrazones fluidized the SC lipids via the disruption of the hydrogen-bonded network formed by polar groups of SC constituents. The relationship between the structure of terpenoid hydrazones and their ability to enhance biomembrane penetration is discussed.


2021 ◽  
Vol 12 ◽  
Author(s):  
Vera Hemleben ◽  
Donald Grierson ◽  
Nikolai Borisjuk ◽  
Roman A. Volkov ◽  
Ales Kovarik

The history of rDNA research started almost 90 years ago when the geneticist, Barbara McClintock observed that in interphase nuclei of maize the nucleolus was formed in association with a specific region normally located near the end of a chromosome, which she called the nucleolar organizer region (NOR). Cytologists in the twentieth century recognized the nucleolus as a common structure in all eukaryotic cells, using both light and electron microscopy and biochemical and genetic studies identified ribosomes as the subcellular sites of protein synthesis. In the mid- to late 1960s, the synthesis of nuclear-encoded rRNA was the only system in multicellular organisms where transcripts of known function could be isolated, and their synthesis and processing could be studied. Cytogenetic observations of NOR regions with altered structure in plant interspecific hybrids and detailed knowledge of structure and function of rDNA were prerequisites for studies of nucleolar dominance, epistatic interactions of rDNA loci, and epigenetic silencing. In this article, we focus on the early rDNA research in plants, performed mainly at the dawn of molecular biology in the 60 to 80-ties of the last century which presented a prequel to the modern genomic era. We discuss – from a personal view – the topics such as synthesis of rRNA precursor (35S pre-rRNA in plants), processing, and the organization of 35S and 5S rDNA. Cloning and sequencing led to the observation that the transcribed and processed regions of the rRNA genes vary enormously, even between populations and species, in comparison with the more conserved regions coding for the mature rRNAs. Epigenetic phenomena and the impact of hybridization and allopolyploidy on rDNA expression and homogenization are discussed. This historical view of scientific progress and achievements sets the scene for the other articles highlighting the immense progress in rDNA research published in this special issue of Frontiers in Plant Science on “Molecular organization, evolution, and function of ribosomal DNA.”


Polymers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 4465
Author(s):  
Georgi B. Hadjichristov ◽  
Todor E. Vlakhov ◽  
Yordan G. Marinov ◽  
Nicola Scaramuzza

Complex electrical impedance and dielectric spectroscopy were applied to study the dielectric relaxations and their thermal behavior in ion-conducting composites/complexes from polymer poly(ethylene oxide) (PEO) and E8 nematic liquid crystals (LCs), at the compositional ratio PEO:E8 = 70:30 wt%. Flexible thin films of PEO/E8 with a thickness of 150 μm were inspected, as well as such films from Na+ ion-conducting electrolyte PEO/E8/NaIO4 with the same PEO:E8 compositional ratio, but additionally containing 10 wt.% from the salt sodium metaperiodate (NaIO4) as a dopant of Na+ ions. The molecular dynamics, namely the dielectric relaxation of PEO/E8 and PEO/E8/NaIO4, were characterized through analyses of complex impedance and dielectric spectra measured in the frequency range of 1 Hz–1 MHz, under variation of temperature from below to above the glass-transition temperature of these composites. The relaxation and polarization of dipole formations in PEO/E8 and PEO/E8/NaIO4 were evidenced and compared in terms of both electrical impedance and dielectric response depending on temperature. The results obtained for molecular organization, molecular relaxation dynamics, and electric polarization in the studied ion-conducting polymer/LC composites/complexes can be helpful in the optimization of their structure and performance, and are attractive for applications in flexible organic electronics, energy storage devices, and mechatronics.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Stephanie Maynard ◽  
Philippe Rostaing ◽  
Natascha Schaefer ◽  
Olivier Gemin ◽  
Adrien Candat ◽  
...  

Precise quantitative information about the molecular architecture of synapses is essential to understanding the functional specificity and downstream signaling processes at specific populations of synapses. Glycine receptors (GlyRs) are the primary fast inhibitory neurotransmitter receptors in the spinal cord and brainstem. These inhibitory glycinergic networks crucially regulate motor and sensory processes. Thus far the nanoscale organization of GlyRs underlying the different network specificities has not been defined. Here, we have quantitatively characterized the molecular arrangement and ultra-structure of glycinergic synapses in spinal cord tissue using quantitative super-resolution correlative light and electron microscopy (SR-CLEM). We show that endogenous GlyRs exhibit equal receptor-scaffold occupancy and constant packing densities of about 2000 GlyRs µm-2 at synapses across the spinal cord and throughout adulthood, even though ventral horn synapses have twice the total copy numbers, larger postsynaptic domains and more convoluted morphologies than dorsal horn synapses. We demonstrate that this stereotypic molecular arrangement is maintained at glycinergic synapses in the oscillator mouse model of the neuromotor disease hyperekplexia despite a decrease in synapse size, indicating that the molecular organization of GlyRs is preserved in this hypomorph. We thus conclude that the morphology and size of inhibitory postsynaptic specializations rather than differences in GlyR packing determine the postsynaptic strength of glycinergic neurotransmission in motor and sensory spinal cord networks.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yukio Cho ◽  
Ty Christoff-Tempesta ◽  
Dae-Yoon Kim ◽  
Guillaume Lamour ◽  
Julia H. Ortony

AbstractSelf-assembly of small molecules in water provides a powerful route to nanostructures with pristine molecular organization and small dimensions (<10 nm). Such assemblies represent emerging high surface area nanomaterials, customizable for biomedical and energy applications. However, to exploit self-assembly, the constituent molecules must be sufficiently amphiphilic and satisfy prescribed packing criteria, dramatically limiting the range of surface chemistries achievable. Here, we design supramolecular nanoribbons that contain: (1) inert and stable internal domains, and (2) sacrificial surface groups that are thermally labile, and we demonstrate complete thermal decomposition of the nanoribbon surfaces. After heating, the remainder of each constituent molecule is kinetically trapped, nanoribbon morphology and internal organization are maintained, and the nanoribbons are fully hydrophobic. This approach represents a pathway to form nanostructures that circumvent amphiphilicity and packing parameter constraints and generates structures that are not achievable by self-assembly alone, nor top-down approaches, broadening the utility of molecular nanomaterials for new targets.


Cell ◽  
2021 ◽  
Author(s):  
Yuhan Wang ◽  
Mark Eddison ◽  
Greg Fleishman ◽  
Martin Weigert ◽  
Shengjin Xu ◽  
...  

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