312 research outputs found

    Evolutionary trends of Famennian icriodids in the Dinant and Vesdre basins (Conodonts, Belgian upper Devonian)

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    Two different probably depth- and/or facies-related morphological groups are recognized within the "shallow water" genus Icriodus of the Belgian Famennian: the "Icriodus alternatus group" dominates in the relatively quiet offshore marine sediments of the Lower Famennian ("Groupe des Schistes de la Famenne "), where as the "Icriodus cornutus-costatus group" characterizes the more nearshore, turbulent facies of the Upper-Famennian ("Groupe des Psammites du Condroz"). A probable endemic morphological evolution is suggested for the latter group. A phylomorphogenetical lineage has been observed between I. alternatus BRANSON & MEHL and I. cornutus SANNEMANN at the base of the Famennian. The interspecific morphological relations and the intraspecific morphological variability within the different Icriodus-stock are discussed. Three new morphotypes of I. alternatus, one new subspecies of I. cornutus and two new subsepcies of I. costatus (THOMAS) are described; their stratigraphical range is discussed

    Inhibition of DNA damage response at telomeres improves the detrimental phenotypes of Hutchinson–Gilford Progeria Syndrome

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    Hutchinson–Gilford progeria syndrome (HGPS) is a genetic disorder characterized by premature aging features. Cells from HGPS patients express progerin, a truncated form of Lamin A, which perturbs cellular homeostasis leading to nuclear shape alterations, genome instability, heterochromatin loss, telomere dysfunction and premature entry into cellular senescence. Recently, we reported that telomere dysfunction induces the transcription of telomeric non-coding RNAs (tncRNAs) which control the DNA damage response (DDR) at dysfunctional telomeres. Here we show that progerin-induced telomere dysfunction induces the transcription of tncRNAs. Their functional inhibition by sequence-specific telomeric antisense oligonucleotides (tASOs) prevents full DDR activation and premature cellular senescence in various HGPS cell systems, including HGPS patient fibroblasts. We also show in vivo that tASO treatment significantly enhances skin homeostasis and lifespan in a transgenic HGPS mouse model. In summary, our results demonstrate an important role for telomeric DDR activation in HGPS progeroid detrimental phenotypes in vitro and in vivo

    Characterization of CuInTe2 thin films prepared by flash evaporation

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    peer reviewedThin films of CuInTe2 were grown by flash evaporation. The influence of the substrate temperature Ts during film deposition on the properties of the thin films was examined. CuInTe2 films were structurally characterized by the grazing incidence x-ray diffraction (GIXD) technique. Investigation by this technique demonstrates that the surface of thin films of CuInTe2 prepared by flash vaporation at Ts > 100 °C exhibits the chalcopyrite structure with additional binary compounds in the surface. However, in the volume the films exhibit the chalcopyrite structure only; no foreign phases were observed. X-ray reflectometry was utilized to evaluate the critical reflection angle bc of CuInTe2 (bCuInTe2 c 0.32°) which permitted us to calculate the density of the films to be 6 g cm−3. The evaporated films were p type and the films deposited at Ts = 100 °C had a resistivity in the range 0.3–2 cm. From optical measurements we have determined the optical energy gap Eg 0.94 eV and the effective reduced mass m*r 0.07me

    Preimplantation genetic testing for more than one genetic condition:clinical and ethical considerations and dilemmas

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    STUDY QUESTION: Which clinical and ethical aspects of preimplantation genetic testing for monogenic disorders or structural rearrangements (PGT-M, PGT-SR) should be considered when accepting requests and counselling couples for PGT when applied for more than one condition (combination-PGT; cPGT-M/SR)? SUMMARY ANSWER: cPGT is a feasible extension of the practice of PGT-M/SR that may require adapting the criteria many countries have in place with regard to indications-setting for PGT-M/SR, while leading to complex choices that require timely counselling and information. WHAT IS KNOWN ALREADY: Although PGT-M/SR is usually performed to prevent transmission of one disorder, requests for PGTM/SR for more than one condition (cPGT-M/SR) are becoming less exceptional. However, knowledge about implications for a responsible application of such treatments is lacking. STUDY DESIGN, SIZE, DURATION: Retrospective review of all (40) PGT-M/SR applications concerning more than one genetic condition over the period 1995-2018 in the files of the Dutch national PGT centre. This comprises all relevant national data since the start of PGT in the Netherlands. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Data regarding cPGT-M/SR cases were collected by means of reviewing medical files of couples applying for cPGT-M/SR. Ethical challenges arising with cPGT-M/SR were explored against the background of PGT-M/SR regulations in several European countries, as well as of relevant ESHRE-guidance regarding both indications-setting and transfer-decisions. MAIN RESULTS AND THE ROLE OF CHANCE: We report 40 couples applying for cPGT-M/SR of which 16 couples started their IVF treatment. Together they underwent 39 IVF cycles leading to the birth of five healthy children. Of the couples applying for cPGT, 45% differentiated between a primary and secondary condition in terms of perceived severity. In the light of an altered balance of benefits and drawbacks, we argue the 'high risk of a serious condition' standard that many countries uphold as governing indications-setting, should be lowered for secondary conditions in couples who already have an indication for PGT-M/SR. As a consequence of cPGT, professionals will more often be confronted with requests for transferring embryos known to be affected with a condition that they were tested for. In line with ESHRE guidance, such transfers may well be acceptable, on the condition of avoiding a high risk of a child with a seriously diminished quality of life. LIMITATIONS, REASONS FOR CAUTION: We are the first to give an overview of cPGT-M/SR treatments. Retrospective analysis was performed using national data, possibly not reflecting current trends worldwide. WIDER IMPLICATIONS OF THE FINDINGS: Our observations have led to recommendations for cPGT-M/SR that may add to centre policy making and to the formulation of professional guidelines. Given that the introduction of generic methods for genomic analysis in PGT will regularly yield incidental findings leading to transfer requests with these same challenges, the importance of our discussion exceeds the present discussion of cPGT

    Accuracy of the new rapid test for monitoring adalimumab levels

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    The loss of response to adalimumab (ADL) has been related to low serum concentrations at trough. Currently, most methods commercially available for the quantification of ADL are enzyme-linked immunosorbent assay (ELISA) based, with a turnaround time of approximately 8 h, delaying the target dosage adjustment to the subsequent infusion. In this study, we aimed to evaluate the performance of the newly available rapid-test ADL quantification assay by comparing it with three established ELISA methods, using spiked samples and a set of clinical samples.info:eu-repo/semantics/publishedVersio

    Telomeric expression sites are highly conserved in trypanosoma brucei

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    Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs) of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs). The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs) were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology
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