Inhaled nitric oxide therapy in neonates and children: reaching a European consensus

Inhaled nitric oxide (iNO) was first used in neonatal practice in 1992 and has subsequently been used extensively in the management of neonates and children with cardiorespiratory failure. This paper assesses evidence for the use of iNO in this population as presented to a consensus meeting jointly organised by the European Society of Paediatric and Neonatal Intensive Care, the European Society of Paediatric Research and the European Society of Neonatology. Consensus Guidelines on the Use of iNO in Neonates and Children were produced following discussion of the evidence at the consensus meeting

Divergent β-hairpins determine double-strand versus single-strand substrate recognition of human AlkB-homologues 2 and 3

Human AlkB homologues ABH2 and ABH3 repair 1-methyladenine and 3-methylcytosine in DNA/RNA by oxidative demethylation. The enzymes have similar overall folds and active sites, but are functionally divergent. ABH2 efficiently demethylates both single- and double-stranded (ds) DNA, whereas ABH3 has a strong preference for single-stranded DNA and RNA. We find that divergent F1 β-hairpins in proximity of the active sites of ABH2 and ABH3 are central for substrate specificities. Swapping F1 hairpins between the enzymes resulted in hybrid proteins resembling the donor proteins. Surprisingly, mutation of the intercalating residue F102 had little effect on activity, while the double mutant V101A/F102A was catalytically impaired. These residues form part of an important hydrophobic network only present in ABH2. In this functionally important network, F124 stacks with the flipped out base while L157 apparently functions as a buffer stop to position the lesion in the catalytic pocket for repair. F1 in ABH3 contains charged and polar residues preventing use of dsDNA substrate. Thus, E123 in ABH3 corresponds to F102 in ABH2 and the E123F-variant gained capacity to repair dsDNA with no loss in single strand repair capacity. In conclusion, divergent sequences outside of the active site determine substrate specificities of ABH2 and ABH3

Positioning Europe for the EPITRANSCRIPTOMICS challenge

The genetic alphabet consists of the four letters: C, A, G, and T in DNA and C,A,G, and U in RNA. Triplets of these four letters jointly encode 20 different amino acids out of which proteins of all organisms are built. This system is universal and is found in all kingdoms of life. However, bases in DNA and RNA can be chemically modified. In DNA, around 10 different modifications are known, and those have been studied intensively over the past 20 years. Scientific studies on DNA modifications and proteins that recognize them gave rise to the large field of epigenetic and epigenomic research. The outcome of this intense research field is the discovery that development, ageing, and stem-cell dependent regeneration but also several diseases including cancer are largely controlled by the epigenetic state of cells. Consequently, this research has already led to the first FDA approved drugs that exploit the gained knowledge to combat disease. In recent years, the ~150 modifications found in RNA have come to the focus of intense research. Here we provide a perspective on necessary and expected developments in the fast expanding area of RNA modifications, termed epitranscriptomics.SCOPUS: no.jinfo:eu-repo/semantics/publishe

Bioinformatics and functional analysis define four distinct groups of AlkB DNA-dioxygenases in bacteria

The iron(II)- and 2-oxoglutarate (2OG)-dependent dioxygenase AlkB from Escherichia coli (EcAlkB) repairs alkylation damage in DNA by direct reversal. EcAlkB substrates include methylated bases, such as 1-methyladenine (m1A) and 3-methylcytosine (m3C), as well as certain bulkier lesions, for example the exocyclic adduct 1,N6-ethenoadenine (εA). EcAlkB is the only bacterial AlkB protein characterized to date, and we here present an extensive bioinformatics and functional analysis of bacterial AlkB proteins. Based on sequence phylogeny, we show that these proteins can be subdivided into four groups: denoted 1A, 1B, 2A and 2B; each characterized by the presence of specific conserved amino acid residues in the putative nucleotide-recognizing domain. A scattered distribution of AlkB proteins from the four different groups across the bacterial kingdom indicates a substantial degree of horizontal transfer of AlkB genes. DNA repair activity was associated with all tested recombinant AlkB proteins. Notably, both a group 2B protein from Xanthomonas campestris and a group 2A protein from Rhizobium etli repaired etheno adducts, but had negligible activity on methylated bases. Our data indicate that the majority, if not all, of the bacterial AlkB proteins are DNA repair enzymes, and that some of these proteins do not primarily target methylated bases

Quantitative EEG findings in patients with acute, brief depression combined with other fluctuating psychiatric symptoms: a controlled study from an acute psychiatric department

<p>Abstract</p> <p>Background</p> <p>Patients with brief depressive episodes and concurrent rapidly fluctuating psychiatric symptoms do not fit current diagnostic criteria and they can be difficult to diagnose and treat in an acute psychiatric setting. We wanted to study whether these patients had signs of more epileptic or organic brain dysfunction than patients with depression without additional symptomatology.</p> <p>Methods</p> <p>Sixteen acutely admitted patients diagnosed with a brief depressive episode as well as another concurrent psychiatric diagnosis were included. Sixteen patients with major depression served as controls. Three electroencephalographic studies (EEG) were visually interpreted and the background activity was also analysed with quantitative electroencephalography (QEEG).</p> <p>Results</p> <p>The group with brief depression and concurrent symptoms had multiple abnormal features in their standard EEG compared to patients with major depression, but they did not show significantly more epileptiform activity. They also had significantly higher temporal QEEG delta amplitude and interhemispheric temporal delta asymmetry.</p> <p>Conclusion</p> <p>Organic brain dysfunction may be involved in the pathogenesis of patients with brief depressive episodes mixed with rapidly fluctuating psychiatric symptoms. This subgroup of depressed patients should be investigated further in order to clarify the pathophysiology and to establish the optimal evaluation scheme and treatment in an acute psychiatric setting.</p

PERANAN PELUKIS ADE MOELYANA DALAM MENGEMBANGKAN SENI LUKIS DARI LIMBAH PELEPAH PISANG DI CIMAHI: (Kajian historis dari tahun 1969-2010)

Skripsi ini berjudul “Peranan Pelukis Ade Moelyana Dalam Mengembangkan Seni Lukis Pelepah Pisang di Cimahi Kajian Historis Tahun 1969-2010”. Permasalahan pokok yang dikaji dalam skripsi ini adalah bagaimana perkembangan seni lukis dari limbah pelepah pisang di Cimahi dari tahun 1969-2010 dan keterkaitannya dengan potensi ekonomi dari seni lukis pelepah pisang yang terabaikan. Metode yang digunakan adalah metode historis yang melalui empat tahap yaitu pengumpulan sumber lisan maupun sumber tertulis, kritik, interpretasi, dan historiografi. Untuk memperdalam analisis, penulis menggunakan pendekatan interdisipliner melalui kajian ilmu sosial dan ilmu ekonomi dengan memakai konsep-konsep seperti interaksi sosial, distribusi, ekonomi kreatif, kewirausahaan, dll. Teknik penelitian yang digunakan dalam penelitian ini adalah dengan menggunakan teknik wawancara. Hal ini dilakukan karena terbatasnya sumber tertulis yang mengkaji secara langsung mengenai permasalahan di atas. Berdasarkan hasil temuan di lapangan, seni lukis dari limbah pelepah pisang ini telah ada sejak tahun 1969. Seni lukis ini merupakan seni lukis yang unik karena menggunakan limbah dari pelepah pisang. Pada awal perkembangannya seni lukis ini tidak serta merta dapat diterima oleh masyarakat sekitar, dan barulah pada tahun 2002 seni lukis dari limbah pelepah pisang ini mengalami puncak perkembangan. Pasalnya seni lukis ini tidak hanya dipasarkan di Cimahi saja, melainkan sampai ke mancanegara. Seni lukis dari limbah pelepah pisang ini dapat dijadikan sebagai sektor ekonomi kreatif dan dapat dijadikan sebagai lahan lapangan pekerjaan. Banyak upaya yang dilakukan oleh pelukis untuk mengembangkan seni lukis dari limbah pelepah pisang, selain itu pula pemerintah turut serta dalam mengembangkan seni lukis pelepah pisang. Kata kunci : Seni Lukis Pelepah Pisang, Ekonomi Kreatif, Pemasaran This skripsi titled Ade Moelyama role in developing the art painting of wasted banana leaves in Cimahi of historical studies from 1969 to 2010. The main issue studied in this skripsi was “How Development Art Painting of Wasted Banana Leaves in Cimahi from 1969 to 2010 and linkages with economic potential of art painting of banana leaves neglected. The method used is the historical method through four phases of heuristics, criticism, interpretation and historiography. To deepen the analysis, the author use the approach interdisciplinary through the study of social and economic by using concepts such as social interaction, distribution, creative economy, entrepreneurship, and other. A research technique used in this research is to use interview techniques. This is done because of the limited resources that examines written directly on the above problems. Based on the research results, the art painting of wasted banana leaves has existed since 1969. This painting is a painting that is unique because it uses waste form banan leaves. In the early development of art is not necessarily acceptable to the local community, and then in 2002 the art painting of wasted banana leaves is experiencing the peak development. This is because not only do marketing painting around Cimahi but abroad as well. Painting of wasted banana stalks can be used as a creative economic sector and creates jobs. Lack of awareness of the various parties to make this painting became dormant. Many attempts were made by the painter to develop the art of waste banana leaves, in addition the goverment also participated in the development the art of painting banana leaves. Keywords : Art Painting of Banana Leaves, Creative Economy, Marketin

Mice Lacking Alkbh1 Display Sex-Ratio Distortion and Unilateral Eye Defects

Escherichia coli AlkB is a 2-oxoglutarate- and iron-dependent dioxygenase that reverses alkylated DNA damage by oxidative demethylation. Mouse AlkB homolog 1 (Alkbh1) is one of eight members of the newly discovered family of mammalian dioxygenases.In the present study we show non-Mendelian inheritance of the Alkbh1 targeted allele in mice. Both Alkbh1(-/-) and heterozygous Alkbh1(+/-) offspring are born at a greatly reduced frequency. Additionally, the sex-ratio is considerably skewed against female offspring, with one female born for every three to four males. Most mechanisms that cause segregation distortion, act in the male gametes and affect male fertility. The skewing of the sexes appears to be of paternal origin, and might be set in the pachythene stage of meiosis during spermatogenesis, in which Alkbh1 is upregulated more than 10-fold. In testes, apoptotic spermatids were revealed in 5-10% of the tubules in Alkbh1(-/-) adults. The deficiency of Alkbh1 also causes misexpression of Bmp2, 4 and 7 at E11.5 during embryonic development. This is consistent with the incompletely penetrant phenotypes observed, particularly recurrent unilateral eye defects and craniofacial malformations.Genetic and phenotypic assessment suggests that Alkbh1 mediates gene regulation in spermatogenesis, and that Alkbh1 is essential for normal sex-ratio distribution and embryonic development in mice