Books in Arabic Script

The chapter approaches the book in Arabic script as the indispensable means for the transmission of knowledge across Eurasia and Africa, within cultures and across cultural boundaries, since the seventh century ad. The state of research can be divided into manuscript and print studies, but there is not yet a history of the book in Arabic script that captures its plurilinear development for over fourteen hundred years. The chapter explores the conceptual and practical challenges that impede the integration of the book in Arabic script into book history at large and includes an extensive reference list that reflects its diversity. The final published version was slightly updated, and includes seven illustrations of six Qurans from the holdings of Columbia University Libraries, four manuscripts and two printed versions. Moreover, the illustrations are images of historical artifacts which are in the public domain - despite Wiley's copyright claim

Severe malaria in Europe: an 8-year multi-centre observational study

Background: Malaria remains one of the most serious infections for travellers to tropical countries. Due to the lack of harmonized guidelines a large variety of treatment regimens is used in Europe to treat severe malaria. Methods: The European Network for Tropical Medicine and Travel Health (TropNet) conducted an 8-year, multicentre, observational study to analyse epidemiology, treatment practices and outcomes of severe malaria in its member sites across Europe. Physicians at participating TropNet centres were asked to report pseudonymized retrospective data from all patients treated at their centre for microscopically confirmed severe Plasmodium falciparum malaria according to the 2006 WHO criteria. Results: From 2006 to 2014 a total of 185 patients with severe malaria treated in 12 European countries were included. Three patients died, resulting in a 28-day survival rate of 98.4%. The majority of infections were acquired in West Africa (109/185, 59%). The proportion of patients treated with intravenous artesunate increased from 27% in 2006 to 60% in 2013. Altogether, 56 different combinations of intravenous and oral drugs were used across 28 study centres. The risk of acute renal failure (36 vs 17% p = 0.04) or cerebral malaria (54 vs 20%, p = 0.001) was significantly higher in patients ≥60 years than in younger patients. Respiratory distress with the need for mechanical ventilation was significantly associated with the risk of death in the study population (13 vs 0%, p = 0.001). Post-artemisinin delayed haemolysis was reported in 19/70 (27%) patients treated with intravenous artesunate. Conclusion: The majority of patients with severe malaria in this study were tourists or migrants acquiring the infection in West Africa. Intravenous artesunate is increasingly used for treatment of severe malaria in many European treatment centres and can be given safely to European patients with severe malaria. Patients treated with intravenous artesunate should be followed up to detect and manage late haemolytic events

Tbx20 Is an Essential Regulator of Embryonic Heart Growth in Zebrafish.

The molecular mechanisms that regulate cardiomyocyte proliferation during embryonic heart growth are not completely deciphered yet. In a forward genetic N-ethyl-N-nitrosourea (ENU) mutagenesis screen, we identified the recessive embryonic-lethal zebrafish mutant line weiches herz (whz). Homozygous mutant whz embryos display impaired heart growth due to diminished embryonic cardiomyocyte proliferation resulting in cardiac hypoplasia and weak cardiac contraction. By positional cloning, we found in whz mutant zebrafish a missense mutation within the T-box 20 (Tbx20) transcription factor gene leading to destabilization of Tbx20 protein. Morpholino-mediated knock-down of Tbx20 in wild-type zebrafish embryos phenocopies whz, indicating that the whz phenotype is due to loss of Tbx20 function, thereby leading to significantly reduced cardiomyocyte numbers by impaired proliferation of heart muscle cells. Ectopic overexpression of wild-type Tbx20 in whz mutant embryos restored cardiomyocyte proliferation and heart growth. Interestingly, ectopic overexpression of Tbx20 in wild-type zebrafish embryos resulted, similar to the situation in the embryonic mouse heart, in significantly reduced proliferation rates of ventricular cardiomyocytes, suggesting that Tbx20 activity needs to be tightly fine-tuned to guarantee regular cardiomyocyte proliferation and embryonic heart growth in vivo

Effects of the <i>whz</i> mutation on embryonic heart morphology and growth.

<p><b>(A-D)</b> Lateral view of wild-type (wt; <b>A, C</b>) and <i>whz</i> mutant (<b>B, D</b>) embryos at 72 hours post fertilization (hpf). <i>Whz</i> mutants show pericardial edema, blood congestion at the cardiac inflow tract and stretched heart chambers. <b>(E, F)</b> Hematoxylin and Eosin staining of sagittal histological sections of wt <b>(E)</b> and <i>whz</i> mutant <b>(F)</b> hearts at 72 hpf. Similar to wild-types, in <i>whz</i> atria and ventricles, myocardial (myo) and endocardial (endo) cell layers are clearly defined and separated by an atrio-ventricular canal (AVC). In contrast to wild-type hearts, <i>whz</i> mutant ventricles appear small and the myocardium monolayered. <b>(G-I)</b> Dissected wt <b>(G)</b> and <i>whz</i> mutant <b>(H)</b> hearts at 72 hpf, stained with a cardiomyocyte-specific MEF-2 antibody (nuclei; red) and co-stained with S46, exclusively marking atrial cardiomyocytes (green)<b>. (I)</b> <i>whz</i> mutant hearts show significantly reduced ventricular cardiomyocytes at 72 hpf (sib: 144.2±10 SD and <i>whz</i>: 94.9±10 SD, n = 10; p<0.0001), whereas cardiomyocyte numbers are comparable between wt and <i>whz</i> ventricles at 48 hpf (wt: 93.4±10 SD and <i>whz</i>: 88.2±10 SD, n = 10; p>0.05).</p

Overexpression of <i>tbx20</i> in wild-type zebrafish embryos results in reduced ventricular cardiomyocyte proliferation.

<p><b>(A, B)</b> Dissected wild-type hearts injected with KCl <b>(A)</b> and <i>tbx20</i> mRNA <b>(B)</b> at 72 hpf, stained against MEF-2 (red) after incorporation of 5-ethynyl-2'-deoxyuridine (EdU; green) to visualize the effect of <i>tbx20</i> overexpression on cardiomyocyte proliferation. <b>(C)</b> Wild-type zebrafish hearts injected with wild-type <i>tbx20</i> mRNA show significantly reduced numbers of ventricular cardiomyocytes at 72 hpf compared to control injected hearts (wt+KCl: 148.6±2.9; wt + <i>tbx20</i> mRNA: 64.0±2.017, n = 10, p< 0.0002). <b>(D)</b> Ventricular cardiomyocyte proliferation in wild-type embryos injected with <i>tbx20</i> mRNA is significantly reduced compared to control injected embryos at 72 hpf (wt+KCl: 8.9 ± 0.38; wt+<i>tbx20</i> mRNA: 1.1±0.28, n = 10, p = 0.0001).</p

The <i>whz</i> mutation interferes with cardiomyocyte proliferation.

<p><b>(A, B)</b> TUNEL stainings of embryonic zebrafish hearts at 72 hpf show no difference in the number of apoptotic cardiomyocytes in wt <b>(A)</b> and <i>whz</i> <b>(B)</b> mutant embryos. TUNEL positive cells in the pericardium (peri) and ventricles are marked by arrows. <b>(C-F)</b> Dissected wt <b>(C)</b> and <i>whz</i> mutant <b>(D)</b> hearts at 72 hpf, stained against MEF-2 (red) after incorporation of 5-ethynyl-2'-deoxyuridine (EdU; green) to visualize cardiomyocyte proliferation. At 48 hpf, proliferation of ventricular cardiomyocytes appears unaltered between wt and <i>whz</i> mutant hearts (sib: 5±2% SD and <i>whz</i>: 4±2% SD, n = 10; p>0.05) <b>(E)</b>, whereas cardiomyocyte proliferation in <i>whz</i> mutant ventricles is significantly reduced compared to wt at 72 hpf (sib: 8±2% SD, <i>whz</i>: 2±2% SD, n = 10, p = 0.0001) <b>(F)</b>.</p

Ectopic expression of wild-type Tbx20 rescues <i>whz</i> mutant embryos.

<p><b>(A, B)</b> Lateral view of <i>whz</i> mutant embryos control-injected with KCl <b>(A)</b> and wild-type zebrafish <i>tbx20</i> mRNA <b>(B)</b>, respectively. <b>(C)</b> Ectopic expression of wild-type zebrafish <i>tbx20</i> mRNA can rescue the heart phenotype of 73% of homozygous <i>whz</i> mutant embryos, whereas injection of KCl has no effect. <b>(D, E)</b> Dissected <i>whz</i> hearts injected with KCl <b>(D)</b> and wild-type <i>tbx20</i> mRNA <b>(E)</b> are stained against MEF-2 (red) after incorporation of 5-ethynyl-2'-deoxyuridine (EdU; green) to visualize cardiomyocyte proliferation. <b>(F)</b> <i>whz</i> mutant hearts injected with wild-type <i>tbx20</i> mRNA show significantly increased numbers of ventricular cardiomyocytes at 72 hpf <b>(E)</b> compared to control-injected <i>whz</i> mutants <b>(D)</b> (<i>whz+tbx20</i> mRNA: 142.5±10 SD, <i>whz</i> + KCl: 87.82±10 SD, n = 10; p = 0.0001). <b>(G)</b> Ventricular cardiomyocyte proliferation in <i>whz</i> mutant embryos injected with <i>tbx20</i> mRNA is significantly enhanced compared to control injected mutants at 72 hpf (<i>whz</i>+<i>tbx20</i> mRNA: 7±3% SD, <i>whz</i>+KCl: 1±2% SD, n = 10; p = 0.0001).</p