TBP2 is a general transcription factor specialized for female germ cells

The complexity of the core promoter transcription machinery has emerged as an additional level of transcription regulation that is used during vertebrate development. Recent studies, including one published in BMC Biology, provide mechanistic insights into how the TATA binding protein (TBP) and its vertebrate-specific paralog TBP2 (TRF3) switch function during the transition from the oocyte to the embryo

A red/far-red light-responsive bi-stable toggle switch to control gene expression in mammalian cells

Growth and differentiation of multicellular systems is orchestrated by spatially restricted gene expression programs in specialized subpopulations. The targeted manipulation of such processes by synthetic tools with high-spatiotemporal resolution could, therefore, enable a deepened understanding of developmental processes and open new opportunities in tissue engineering. Here, we describe the first red/far-red light-triggered gene switch for mammalian cells for achieving gene expression control in time and space. We show that the system can reversibly be toggled between stable on- and off-states using short light pulses at 660 or 740 nm. Red light-induced gene expression was shown to correlate with the applied photon number and was compatible with different mammalian cell lines, including human primary cells. The light-induced expression kinetics were quantitatively analyzed by a mathematical model. We apply the system for the spatially controlled engineering of angiogenesis in chicken embryos. The system's performance combined with cell- and tissue-compatible regulating red light will enable unprecedented spatiotemporally controlled molecular interventions in mammalian cells, tissues and organisms

Zebrafish regulatory genomic resources for disease modelling and regeneration

In the past decades, the zebrafish has become a disease model with increasing popularity owing to its advantages that include fast development, easy genetic manipulation, simplicity for imaging, and sharing conserved disease-associated genes and pathways with those of human. In parallel, studies of disease mechanisms are increasingly focusing on non-coding mutations, which require genome annotation maps of regulatory elements, such as enhancers and promoters. In line with this, genomic resources for zebrafish research are expanding, producing a variety of genomic data that help in defining regulatory elements and their conservation between zebrafish and humans. Here, we discuss recent developments in generating functional annotation maps for regulatory elements of the zebrafish genome and how this can be applied to human diseases. We highlight community-driven developments, such as DANIO-CODE, in generating a centralised and standardised catalogue of zebrafish genomics data and functional annotations; consider the advantages and limitations of current annotation maps; and offer considerations for interpreting and integrating existing maps with comparative genomics tools. We also discuss the need for developing standardised genomics protocols and bioinformatic pipelines and provide suggestions for the development of analysis and visualisation tools that will integrate various multiomic bulk sequencing data together with fast-expanding data on single-cell methods, such as single-cell assay for transposase-accessible chromatin with sequencing. Such integration tools are essential to exploit the multiomic chromatin characterisation offered by bulk genomics together with the cell-type resolution offered by emerging single-cell methods. Together, these advances will build an expansive toolkit for interrogating the mechanisms of human disease in zebrafish

Recognizing design patterns in C++ programs with the integration of Columbus and Maisa

A method for recognizing design patterns from C++ programs is presented. The method consists of two separate phases, analysis and reverse engineering of the C++ code, and architectural pattern matching over the reverse-engineered intermediate code representation. It is shown how the pattern recognition effect can be realized by integrating two specialized software tools, the reverse engineering framework Columbus and the architectural metrics analyzer Maisa. The method and the integrated power of the tool set are illustrated with small experiments

Identification of near-surface saline water in the Lake Kelemenszék area, Danube-Tisza Interfluve, Hungary

Abstract In the Danube Valley, a chain of saline lakes and a salinized area are situated in the discharge zone of two different waters. The two watertype were followed till the near surface by regional chemical and hydraulic investigations (Mádlné Szőnyi and Tóth 2009). The goals of this study were to prove the presence of these different waters in the near surface zone around the Lake Kelemenszék, and allocate their connection to the lake and to the salinized ground surface. Near-surface geophysical measurements (VES, RMT) supported the regional hydraulic and chemical results. The sediments are saturated by saline water down to 110 m beneath the lake, and to the east the fresh water is prevalent. The local chemical investigations strengthened this distribution. Highly saline water with Na-HCO3-Cl-type discharges into and around the lake. To the east there is a continuous change towards a (Ca,Mg)-(HCO3)2-type fresh water discharge. The interface between the two water types is a 2–3 km wide transition zone. The results of the investigations proved that the saline water of the deep flow system rises to the surface and provide salt for the salinization of the area

Impact of diabetes mellitus on long-term outcome after unstable angina and non-ST-segment elevation myocardial infarction treated with a very early invasive strategy

Aims/hypothesis: We sought to evaluate the impact of diabetes mellitus on long-term outcome in patients with unstable angina and non-ST-segment elevation myocardial infarction treated with a very early invasive strategy. Methods: We carried out a prospective cohort study in 270 diabetic and 1163 non-diabetic patients with unstable angina and non-ST-segment elevation myocardial infarction. All patients underwent coronary angiography and, if appropriate, subsequent revascularisation within 24 hours of admission. The primary endpoint was all-cause mortality during follow-up for up to 60 months. Results: Diabetic patients had less favourable baseline characteristics including more advanced coronary artery disease and more severe unstable angina and non-ST-segment elevation myocardial infarction. Percutaneous coronary intervention was performed in 53% of diabetic patients and 56% of non-diabetic patients. Coronary artery bypass grafting was done in 21% of diabetic patients and 12% of non-diabetic patients. In-hospital mortality (4.1% vs 1.3%; hazard ratio 3.47; 95% CI: 1.57 to 7.64; p=0.002) and long-term mortality (9.7% vs 4.9%; hazard ratio 2.11; 95% CI: 1.33 to 3.36; p=0.002) were significantly higher in diabetic patients. After adjustment for differences in baseline characteristics, diabetes mellitus was no longer an independent predictor of long-term mortality (hazard ratio 1.43; 95% CI: 0.74 to 2.78; p=0.292). Conclusions/interpretation: Diabetic patients treated with a very early invasive strategy for unstable angina and non-ST-segment elevation myocardial infarction have a higher in-hospital and long-term mortality that is largely explained by their less favourable baseline characteristics including more advanced coronary artery disease and more severe unstable angina and non-ST-segment elevation myocardial infarctio

Élelmiszer eredetű bakteriális megbetegedések patogenezise, klinikai jellegzetességei, diagnosztikája és kezelése

Az élelmiszer-eredetű megbetegedések igen gyakoriak, bár pontos adatok nem állnak rendelkezésre, mivel az enyhe, gyorsan múló gastrointestinalis tünetekkel a betegek nem fordulnak orvoshoz, vagy nem történik diagnosztikus vizs- gálat. Az amerikai Járványügyi és Betegségmegelőzési Központ (CDC) adatai szerint az USA-ban évente 6 lakosból 1 esik át élelmiszer okozta tüneteken. Az ételintoxikációk során a baktérium által termelt toxinok okozzák a tünete- ket, közülük a leggyakoribb a Clostridium perfringens, a Staphylococcus aureus és a Bacillus cereus okozta, élelmiszer- eredetű intoxikáció. A nem megfelelően tárolt vagy hőkezelt élelmiszerekben – beleértve a S. aureus által szennyezett anyatejet – ezen baktériumok életképesek maradnak, elszaporodnak, és toxint termelhetnek, illetve toxinjaik megőr- zik megbetegítőképességüket. Az étel elfogyasztása után 3–12 órával hányást, hasmenést okoznak. A tünetek több- nyire 24 órán belül megszűnnek. A Clostridium botulinum súlyos neurológiai tünetei miatt emelkedik ki a többi toxikoinfekció sorából. C. botulinum okozta tünetekre felnőtteknél házi készítésű konzervek és húskészítmények elfogyasztása után jelentkező gastrointestinalis vagy neurológiai tünetek esetén kell gondolnunk. A Clostridioides difficile szintén a toxinjai révén okoz súlyos, életveszélyes megbetegedést, továbbá az esetek 20–30%-ában számol- nunk kell az infekció relapsusával. Növekvő gyakorisága miatt ismernünk érdemes a laboratóriumi és klinikai diag- nosztika részleteit és a legmodernebb kezelési lehetőségeket, úgymint megfelelő mintavétel, mintatárolás és -szállítás, tenyésztés, toxinkimutatás, helyes tüneti kezelés, antibiotikumkombinációk, széklettranszplantáció és monoklonális- antitest-kezelés