Fammenian

The name of the Famennian stage originated in the 19th century from the Famenne region in southern Belgium. After the pioneering work of Dumont, d'Omalius d'Halloy, Gosselet and Mourlon, a renewed interest in the 1960’s focused mainly on the lithological, sedimentological, paleontological and palynological characteristics of the Famennian. This resulted in a refined litho- and biostratigraphical framework for the Lower Famennian Famenne Shales and the Upper Famennian Condroz Sandstones in Belgium. The most obvious finding was the distinct diachronous character of the Condroz Group. The present review paper extends this stratigraphical framework into the neighbouring Avesnois (Northern France) and Aachen (Northwestern Germany) areas: it proposes a lithostratigraphical correlation between the units identified within the individual tectonic units. An overview is given of the main lithological-sedimentological characteristics, depositional environments (for both the siliciclastics and the carbonates) and prevailing paleogeographical-paloeclimatological conditions, during the Famennian stage in Belgium and adjacent areas

Telomere structure and shortening in telomerase-deficient Trypanosoma brucei

Telomerase consists of a reverse transcriptase (TERT) and an RNA that contains a template for telomere-repeat extension. Telomerase is required to prevent telomere erosion and its activity or lack thereof is important for tumorigenesis and ageing. Telomerase has been identified in numerous organisms but it has not been studied in kinetoplastid protozoa. Trypanosoma brucei, the causative agent of African sleeping sickness, evades the host immune response by frequently changing its variant surface glycoprotein (VSG). The single expressed VSG is transcribed from one of ∼20 subtelomeric ‘Expression Sites’, but the role telomeres might play in regulating VSG transcription and switching is unknown. We identified and sequenced the T.brucei TERT gene. Deleting TERT resulted in progressive telomere shortening of 3–6 bp per generation. In other organisms, the rate of telomere shortening is proportional to the length of the terminal 3′ single-strand overhang. In T.brucei, G-overhangs were undetectable (<30 nt) by in-gel hybridization. The rate of telomere shortening therefore, agrees with the predicted shortening due to the end replication problem, and is consistent with our observation that G-overhangs are short. Trypanosomes whose telomere length can be manipulated provide a new tool to investigate the role of telomeres in antigenic variation

The Devono-Carboniferous transition in the Franco-Belgian basin with reference to Foraminifera and Brachiopods

After a brief summary of the most striking evolutionary trends of the Upper Frasnian through Lower Tournaisian foraminifer assemblages in Northwestern Europe, some new biostratigraphic data are discussed mainly from an important section near St. Hilaire (Avesnois area, Northern France) as well as their impact on the problem of the Devono-Carboniferous boundary in the Franco-Belgian Basin

High-precision performance testing of the LHC power converters

The magnet power converters for LHC were procured in three parts, power part, current transducers and control electronics, to enable a maximum of industrial participation in the manufacturing and still guarantee the very high precision (a few parts in 10-6) required by LHC. One consequence of this approach was several stages of system tests: factory reception tests, CERN reception tests, integration tests , short-circuit tests and commissioning on the final load in the LHC tunnel. The majority of the power converters for LHC have now been delivered, integrated into complete converter and high-precision performance testing is well advanced. This paper presents the techniques used for high-precision testing and the results obtained

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

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

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

Hydraulic hammer drilling technology: Developments and capabilities

Percussion drilling technology was considered many years ago as one of the best approaches for hard rock drilling. Unfortunately the efficiency of most hydraulic hammer (HH) designs was very low (8% maximum), so they were successfully used in shallow boreholes only. Thirty years of research and field drilling experience with HH application in Former Soviet Union (FSU) countries led to the development of a new generation of HH designs with a proven efficiency of 40%. That advance achieved good operational results in hard rock at depths up to 2,000 m and more. The most recent research has shown that there are opportunities to increase HH efficiency up to 70%. This paper presents HH basic design principles and operational features. The advantages of HH technology for coiled-tubing drilling is shown on the basis of test results recently conducted in the US

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

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

Telomeric expression sites are highly conserved in trypanosoma brucei

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

Preimplantation Genetic Testing for Monogenic Kidney Disease

BACKGROUND AND OBJECTIVES: A genetic cause can be identified for an increasing number of pediatric and adult-onset kidney diseases. Preimplantation genetic testing (formerly known as preimplantation genetic diagnostics) is a reproductive technology that helps prospective parents to prevent passing on (a) disease-causing mutation(s) to their offspring. Here, we provide a clinical overview of 25 years of preimplantation genetic testing for monogenic kidney disease in The Netherlands. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a retrospective cohort study of couples counseled on preimplantation genetic testing for monogenic kidney disease in the national preimplantation genetic testing expert center (Maastricht University Medical Center+) from January 1995 to June 2019. Statistical analysis was performed through chi-squared tests. RESULTS: In total, 98 couples were counseled regarding preimplantation genetic testing, of whom 53% opted for preimplantation genetic testing. The most frequent indications for referral were autosomal dominant polycystic kidney disease (38%), Alport syndrome (26%), and autosomal recessive polycystic kidney disease (9%). Of couples with at least one preimplantation genetic testing cycle with oocyte retrieval, 65% experienced one or more live births of an unaffected child. Of couples counseled, 38% declined preimplantation genetic testing for various personal and technical reasons. CONCLUSIONS: Referrals, including for adult-onset disease, have increased steadily over the past decade. Though some couples decline preimplantation genetic testing, in the couples who proceed with at least one preimplantation genetic testing cycle, almost two thirds experienced at least one live birth rate