scholarly journals Evolutionary mode for the functional preservation of fast-evolving Drosophila telomere capping proteins

Open Biology ◽  
2021 ◽  
Vol 11 (11) ◽  
Author(s):  
Balázs Vedelek ◽  
Ákos Kovács ◽  
Imre M. Boros
Keyword(s):  
Three Dimensional ◽  
Genome Replication ◽  
Telomeric Dna ◽  
Ssdna Binding ◽  
Capping Proteins ◽  
Accelerated Evolution ◽  
Telomere Biology ◽  
Three Dimensional Models ◽  
Interacting Surfaces

DNA end protection is fundamental for the long-term preservation of the genome. In vertebrates the Shelterin protein complex protects telomeric DNA ends, thereby contributing to the maintenance of genome integrity. In the Drosophila genus, this function is thought to be performed by the Terminin complex, an assembly of fast-evolving subunits. Considering that DNA end protection is fundamental for successful genome replication, the accelerated evolution of Terminin subunits is counterintuitive, as conservation is supposed to maintain the assembly and concerted function of the interacting partners. This problem extends over Drosophila telomere biology and provides insight into the evolution of protein assemblies. In order to learn more about the mechanistic details of this phenomenon we have investigated the intra- and interspecies assemblies of Verrocchio and Modigliani, two Terminin subunits using in vitro assays. Based on our results and on homology-based three-dimensional models for Ver and Moi, we conclude that both proteins contain Ob-fold and contribute to the ssDNA binding of the Terminin complex. We propose that the preservation of Ver function is achieved by conservation of specific amino acids responsible for folding or localized in interacting surfaces. We also provide here the first evidence on Moi DNA binding.

ANCD thrombectomy device: in vitro evaluation

2019 ◽  
Vol 12 (1) ◽  
pp. 77-81 ◽  
Author(s):  
Sonia Sanchez ◽  
Ignacio Cortiñas ◽  
Helena Villanova ◽  
Anna Rios ◽  
Iñaki Galve ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Treatment Strategies ◽  
Local Flow ◽  
Guide Catheter ◽  
First Pass ◽  
Thrombectomy Device ◽  
The Mean ◽  
Three Dimensional Models ◽  
Number Of Passes

IntroductionEndovascular treatment of stroke, although highly effective, may fail to reach complete recanalization in around 20% of cases. The Advanced Thrombectomy System (ANCD) is a novel stroke thrombectomy device designed to reduce clot fragmentation and facilitate retrieval by inducing local flow arrest and allowing distal aspiration in combination with a stent retriever. We aimed to assess the preclinical efficacy of ANCD.MethodsSoft red blood cell (RBC)-rich (n=20/group) and sticky fibrin-rich (n=30/group) clots were used to create middle cerebral artery (MCA) occlusions in two vascular phantoms. Three different treatment strategies were tested: (1) balloon guide catheter + Solitaire (BGC+SR); (2) distal access catheter + SR (DAC+SR); and (3) ANCD+SR, until complete recanalization was achieved or to a maximum of three passes. The recanalization rate was determined after each pass.ResultsAfter one pass, ANCD+SR resulted in an increased recanalization rate (94%) for all clots together compared with BGC+SR (66%; p<0.01) or DAC+SR (80%; p=0.04). After the final pass the recanalization rate increased in all three groups but remained higher with ANCD+SR (100%) than with BGC+SR (74%; p<0.01) or DAC+SR (90%; p=0.02). The mean number of passes was lower with ANCD+SR (1.06) than with BGC+SR (1.46) or DAC+SR (1.25) (p=0.01). A logistic regression model adjusted for treatment arm, clot type, and model used showed that both RBC-rich clots (OR 8.1, 95% CI 1.6 to 13.5) and ANCD+SR (OR 3.9, 95% CI 1.01 to 15.8) were independent predictors of first-pass recanalization.ConclusionIn in vitro three-dimensional models replicating MCA-M1 occlusion, ANCD+SR showed significantly better recanalization rates in fewer passes than other commonly used combinations of devices.

The effect of temperature on in vitro germination and germ tube growth of urediniospores of Tranzschelia discolor

1990 ◽  
Vol 41 (3) ◽  
pp. 479 ◽  
Author(s):  
PJ Ellison ◽  
BR Cullis ◽  
RW Bambach ◽  
PF Kable
Keyword(s):  
Germ Tube ◽  
Three Dimensional ◽  
Tube Growth ◽  
Effect Of Temperature ◽  
In Vitro Germination ◽  
Three Dimensional Models ◽  
C 30 ◽  
Tranzschelia Discolor ◽  
Germ Tube Growth

The effect of temperature on in vitro germination and germ tube growth of urediniospores of Tranzschelia discolor was studied over time under constant temperature conditions. Studies were carried out on 1% water agar in the dark at 3�C, 5�C, 8�C, 10�C, 15�C, 20�C, 25�C, 28�C, 30�C and 32�C. Germination was observed at all temperatures between 5 and 30'C, and occurred rapidly over most of this range. At 2 h, germination exceeded 80% at temperatures between 10 and 28�C, and this level was reached at 3 h at 8�C. Germination at 5 and 30�C was much reduced and at 7 h reached only 44% and 38% respectively. Germ tube growth occurred most vigorously at 15 and 20�C, reaching lengths in excess of 500 8m at 9 h. The optimum range was narrower than that for germination, and growth was reduced or poor at 8�C, 10�C, 25�C and 28�C, which were favourable temperatures for germination. Average germ tube lengths at 9 h at these temperatures were 55, 245, 273 and 62 8m, respectively. Three-dimensional models were derived relating germination and germ tube growth to time and temperature.

scholarly journals G-Quadruplexes at Telomeres: Friend or Foe?

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3686 ◽  
Author(s):  
Tracy M. Bryan
Keyword(s):  
Tandem Repeats ◽  
Genome Instability ◽  
Protein Complexes ◽  
Telomere Maintenance ◽  
Telomeric Dna ◽  
Positive Role ◽  
Telomere Biology ◽  
Linear Chromosomes

Telomeres are DNA-protein complexes that cap and protect the ends of linear chromosomes. In almost all species, telomeric DNA has a G/C strand bias, and the short tandem repeats of the G-rich strand have the capacity to form into secondary structures in vitro, such as four-stranded G-quadruplexes. This has long prompted speculation that G-quadruplexes play a positive role in telomere biology, resulting in selection for G-rich tandem telomere repeats during evolution. There is some evidence that G-quadruplexes at telomeres may play a protective capping role, at least in yeast, and that they may positively affect telomere maintenance by either the enzyme telomerase or by recombination-based mechanisms. On the other hand, G-quadruplex formation in telomeric DNA, as elsewhere in the genome, can form an impediment to DNA replication and a source of genome instability. This review summarizes recent evidence for the in vivo existence of G-quadruplexes at telomeres, with a focus on human telomeres, and highlights some of the many unanswered questions regarding the location, form, and functions of these structures.

scholarly journals LKB1 kinase-dependent and -independent defects disrupt polarity and adhesion signaling to drive collagen remodeling during invasion

2016 ◽  
Vol 27 (7) ◽  
pp. 1069-1084 ◽  
Author(s):  
Jessica Konen ◽  
Scott Wilkinson ◽  
Byoungkoo Lee ◽  
Haian Fu ◽  
Wei Zhou ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Cancer Metastasis ◽  
Kinase Activity ◽  
Rho Gtpase ◽  
Three Dimensional ◽  
Serine Threonine Kinase ◽  
Collagen Remodeling ◽  
Threonine Kinase ◽  
Three Dimensional Models

LKB1 is a serine/threonine kinase and a commonly mutated gene in lung adenocarcinoma. The majority of LKB1 mutations are truncations that disrupt its kinase activity and remove its C-terminal domain (CTD). Because LKB1 inactivation drives cancer metastasis in mice and leads to aberrant cell invasion in vitro, we sought to determine how compromised LKB1 function affects lung cancer cell polarity and invasion. Using three-dimensional models, we show that LKB1 kinase activity is essential for focal adhesion kinase–mediated cell adhesion and subsequent collagen remodeling but not cell polarity. Instead, cell polarity is overseen by the kinase-independent function of its CTD and more specifically its farnesylation. This occurs through a mesenchymal-amoeboid morphological switch that signals through the Rho-GTPase RhoA. These data suggest that a combination of kinase-dependent and -independent defects by LKB1 inactivation creates a uniquely invasive cell with aberrant polarity and adhesion signaling that drives invasion into the microenvironment.

scholarly journals The domain architecture of JBP1 suggests synergy between J-base DNA binding and thymidine hydroxylase activity

2018 ◽  
Author(s):  
Athanassios Adamopoulos ◽  
Tatjana Heidebrecht ◽  
Jeroen Roosendaal ◽  
Wouter G Touw ◽  
Isabelle Phan ◽  
...  
Keyword(s):  
Dna Binding ◽  
Domain Architecture ◽  
Three Dimensional ◽  
Specific Sequence ◽  
X Ray ◽  
Tet Proteins ◽  
X Ray Scattering ◽  
Sequence Patterns ◽  
Three Dimensional Models

JBP1 (J-DNA Binding Protein 1) contributes to biosynthesis and maintenance of base J (β-D-glucosyl-hydroxymethyluracil), a modification of thymidine (T) confined to pathogenic protozoa. JBP1 has two known functional domains: an N-terminal thymidine hydroxylase (TH) homologous to the 5-methylcytosine hydroxylase domain in TET proteins; and a J-DNA binding domain (JDBD) that resides in the middle of JBP1. Here we show that removing JDBD from JBP1 results in a soluble protein (Δ-JDBD) with the N- and C-terminal regions tightly associated together in a well-ordered domain. This Δ-JDBD domain retains thymidine hydroxylation activity in vitro, but displays a fifteen-fold lower apparent rate of hydroxylation compared to JBP1. Small Angle X-ray Scattering (SAXS) experiments on JBP1 and JDBD in the presence and absence of J-DNA, and on Δ-JDBD, allowed us to generate low-resolution three-dimensional models. We conclude that Δ-JDBD, and not the N-terminal region of JBP1 alone, is a distinct folding unit. Our SAXS-based model supports the notion that binding of JDBD specifically to J-DNA can facilitate hydroxylation a T 12-14 bp downstream on the complementary strand of the J-recognition site. We postulate that insertion of the JDBD module in the Δ-JDBD scaffold during evolution provided a mechanism to synergize between J recognition and T hydroxylation, ensuring inheritance of J in specific sequence patterns following DNA replication.

scholarly journals Shear bond strength of ceramic laminate veneers to finishing surfaces with different percentages of preserved enamel under a digital guided method

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Jiakang Zhu ◽  
Jing Gao ◽  
Luming Jia ◽  
Xin Tan ◽  
Chenyang Xie ◽  
...  
Keyword(s):  
Bond Strength ◽  
Shear Bond Strength ◽  
Three Dimensional ◽  
In Vitro Study ◽  
Significant Difference ◽  
Dimensional Models ◽  
Three Dimensional Models ◽  
Laminate Veneers ◽  
Bonding Surface

Abstract Background The purpose of this in vitro study was to evaluate the effect of the percentages of preserved enamel on ceramic laminate veneers’ (CLVs) shear bond strength (SBS). Methods Seventy extracted human maxillary central incisors were scanned and reconstructed into three-dimensional models. The extracted teeth were then embedded and randomly divided into seven groups (n = 10 per group). Based on digital analyses of the three-dimensional models, guided tooth preparation and bonding procedures were performed individually to form seven different percentages (100%, 80%, 60% 50%, 40%, 20% and 0%) of remaining enamel thickness on the bonding surface. Finally, the SBS test was performed, and the data were statistically analysed by one-way ANOVA with LSD post hoc test (α = 0.05). Results The complete enamel surface exhibited the highest SBS (19.93 ± 4.55 MPa), followed by 80% enamel (19.03 ± 3.66 MPa), 60% enamel (18.44 ± 3.65 MPa), 50% enamel (18.18 ± 3.41 MPa), 40% enamel (17.83 ± 3.01 MPa) and 20% enamel (11.32 ± 3.42 MPa) group. The lowest SBS (9.63 ± 3.46 MPa) was detected in 0% enamel group. No significant difference was observed among the 40–100% enamel groups, while the 20% or 0% enamel group demonstrated a significantly lower mean SBS than the 40% enamel group (p < 0.05). Conclusion The SBS value of CLVs bonded to 100% enamel on the finishing surfaces (nearly 20 MPa) was twice that which bonded to 0% enamel (nearly 10 MPa). Bonding to 100% enamel is the most reliable treatment. When dentin exposure is inevitable, enamel should be preserved as much as possible to maintain good bonding. In addition, 40% of preserved enamel on the bonding surface was the minimal acceptable value to fulfil the requirements of good bonding strength.

scholarly journals Virulence of the Fungal Pathogen Candida albicans Requires the Five Isoforms of Protein Mannosyltransferases

2005 ◽  
Vol 73 (8) ◽  
pp. 4571-4580 ◽  
Author(s):  
Mahmoud Rouabhia ◽  
Martin Schaller ◽  
Cristina Corbucci ◽  
Anna Vecchiarelli ◽  
Stephan K.-H. Prill ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Mouse Model ◽  
Fungal Pathogen ◽  
Antifungal Agents ◽  
Three Dimensional ◽  
Secretory Proteins ◽  
In Vitro Growth ◽  
Specific Host ◽  
Three Dimensional Models

ABSTRACT The PMT gene family in Candida albicans encodes five isoforms of protein mannosyltransferases (Pmt proteins Pmt1p, Pmt2p, Pmt4p, Pmt5p, and Pmt6p) that initiate O mannosylation of secretory proteins. We compared virulence characteristics of pmt mutants in two complex, three-dimensional models of localized candidiasis, using reconstituted human epithelium (RHE) and engineered human oral mucosa (EHOM); in addition, mutants were tested in a mouse model of hematogenously disseminated candidiasis (HDC). All pmt mutants showed attenuated virulence in the HDC model and at least one model of localized candidiasis. The pmt5 mutant, which lacks in vitro growth phenotypes, was less virulent in the EHOM and HDC assays but had no consistent phenotype in the RHE assay. In contrast, the pmt4 and pmt6 mutants were less virulent in the RHE and HDC assays but not in the EHOM assay. The results stress the contribution of all Pmt isoforms to the virulence of C. albicans and suggest that the importance of individual Pmt isoforms may differ in specific host niches. We propose that Pmt proteins may be suitable targets for future novel classes of antifungal agents.

ten years of modelling to achieve haemodynamic optimisation of the total cavopulmonary connection

2004 ◽  
Vol 14 (S3) ◽  
pp. 48-52 ◽  
Author(s):  
gabriele dubini ◽  
francesco migliavacca ◽  
giancarlo pennati ◽  
marc r. de leval ◽  
edward l. bove
Keyword(s):  
Fluid Dynamics ◽  
Computational Fluid Dynamics ◽  
Cardiovascular System ◽  
Three Dimensional ◽  
In Vitro Models ◽  
Surgical Reconstruction ◽  
Complex Anatomy ◽  
Recent Developments ◽  
Three Dimensional Models

the techniques of computational fluid dynamics are among the most powerful tools available to engineers dealing with the motion of fluids and the exchange of mass, momentum, and energy. they have recently been shown to have an increasing number of applications to the human cardiovascular system, including the fluid dynamics of surgical reconstruction of congenitally malformed parts of the cardiovascular system. in vitro models are the alternative laboratory tools with which to study fluid dynamics. the advantages of computational fluid dynamics over the in vitro models are the easy quantification of haemodynamic variables, such as rates of flow, pressure, and distribution of shear stress, and changes in geometric and fluid dynamics parameters. furthermore, using computational fluid dynamics allows the development of three-dimensional models to reproduce both the complex anatomy of the investigated region and the details of the surgical reconstruction, especially with the recent developments in magnetic resonance imaging. on the basis of the results, it is possible quantitatively to evaluate the surgical correction. this technology, which benefits greatly from the continuous improvement in hardware and software, enables cardiovascular experts and bioengineers to look at the fluid dynamics of various cardiovascular regions with increasing sophistication.

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