(S)-Benzyl 2-amino-3-(4-hydroxy­phen­yl)propanoate

The title compound, C16H17NO3, adopts a folded conformation in the crystal structure. The crystal packing is stabilized by inter­molecular O—H⋯O and N—H⋯O hydrogen-bonding inter­actions. The absolute configuration was assigned assuming that the absolute configuration of the starting material l-tyrosine was retained during the synthesis

Collaborating to safeguard children in Taiwan: Systemic transformation

Child abuse and exploitation pose significant threats to the health and well-being of children. While the Taiwanese government introduced the Protection of Children and Youth Welfare and Rights Act in 2011 to address these issues, progress has been slow. This paper aims to examine the evolution of Taiwan’s child protection system (CPS), with a particular focus on interdepartmental collaboration. Through the collection of legislation, statistics, conference proceedings, and reports, this study analyzes the working model between law enforcement and public health. Three cases of collaboration between law enforcement and public health at the community level are presented: social safety net programs, early intervention for child abuse, and trauma-informed training for first responders. The accomplishments and challenges of each project are discussed, along with a review of the CPS in relation to the United Nations (UN) strategy INSPIRE’s approaches. Although Taiwan has shown a commendable emphasis on prevention and family support, the collaboration between law enforcement and public health is still in its early stages. The next crucial step is to strengthen integration in the early stages of identifying, assessing, and referring cases of child abuse and neglect. This can be achieved by generating more evidence on effective working models and promoting their implementation

Ample Pairs

We show that the ample degree of a stable theory with trivial forking is preserved when we consider the corresponding theory of belles paires, if it exists. This result also applies to the theory of $H$-structures of a trivial theory of rank $1$.Comment: Research partially supported by the program MTM2014-59178-P. The second author conducted research with support of the programme ANR-13-BS01-0006 Valcomo. The third author would like to thank the European Research Council grant 33882

Altered MICOS Morphology and Mitochondrial Ion Homeostasis Contribute to Poly(GR) Toxicity Associated with C9-ALS/FTD

Amyotrophic lateral sclerosis (ALS) manifests pathological changes in motor neurons and various other cell types. Compared to motor neurons, the contribution of the other cell types to the ALS phenotypes is understudied. G4C2 repeat expansion in C9ORF72 is the most common genetic cause of ALS along with frontotemporal dementia (C9-ALS/FTD), with increasing evidence supporting repeat-encoded poly(GR) in disease pathogenesis. Here, we show in Drosophila muscle that poly(GR) enters mitochondria and interacts with components of the Mitochondrial Contact Site and Cristae Organizing System (MICOS), altering MICOS dynamics and intra-subunit interactions. This impairs mitochondrial inner membrane structure, ion homeostasis, mitochondrial metabolism, and muscle integrity. Similar mitochondrial defects are observed in patient fibroblasts. Genetic manipulation of MICOS components or pharmacological restoration of ion homeostasis with nigericin effectively rescue the mitochondrial pathology and disease phenotypes in both systems. These results implicate MICOS-regulated ion homeostasis in C9-ALS pathogenesis and suggest potential new therapeutic strategies

β-Lapachone induces heart morphogenetic and functional defects by promoting the death of erythrocytes and the endocardium in zebrafish embryos

<p>Abstract</p> <p>Background</p> <p>β-Lapachone has antitumor and wound healing-promoting activities. To address the potential influences of various chemicals on heart development of zebrafish embryos, we previously treated zebrafish embryos with chemicals from a Sigma LOPAC1280™ library and found several chemicals including β-lapachone that affected heart morphogenesis. In this study, we further evaluated the effects of β-lapachone on zebrafish embryonic heart development.</p> <p>Methods</p> <p>Embryos were treated with β-lapachone or dimethyl sulfoxide (DMSO) at 24 or 48 hours post fertilization (hpf) for 4 h at 28°C. Heart looping and valve development was analyzed by whole-mount <it>in situ </it>hybridization and histological analysis. For fractional shortening and wall shear stress analyses, AB and Tg (<it>gata1</it>:<it>DsRed</it>) embryos were recorded for their heart pumping and blood cell circulations via time-lapse fluorescence microscopy. Dextran rhodamine dye injection into the tail reticular cells was used to analyze circulation. Reactive oxygen species (ROS) was analyzed by incubating embryos in 5-(and 6-)-chloromethyl-2',7'-dichloro-dihydrofluorescein diacetate (CM-H₂DCFDA) and recorded using fluorescence microscopy. <it>o</it>-Dianisidine (ODA) staining and whole mount <it>in situ </it>hybridization were used to analyze erythrocytes. TUNEL assay was used to examine DNA fragmentation.</p> <p>Results</p> <p>We observed a linear arrangement of the ventricle and atrium, bradycardia arrhythmia, reduced fractional shortening, circulation with a few or no erythrocytes, and pericardial edema in β-lapachone-treated 52-hpf embryos. Abnormal expression patterns of <it>cmlc2</it>, <it>nppa</it>, <it>BMP4</it>, <it>versican</it>, and <it>nfatc1</it>, and histological analyses showed defects in heart-looping and valve development of β-lapachone-treated embryos. ROS production was observed in erythrocytes and DNA fragmentation was detected in both erythrocytes and endocardium of β-lapachone-treated embryos. Reduction in wall shear stress was uncovered in β-lapachone-treated embryos. Co-treatment with the NQO1 inhibitor, dicoumarol, or the calcium chelator, BAPTA-AM, rescued the erythrocyte-deficiency in circulation and heart-looping defect phenotypes in β-lapachone-treated embryos. These results suggest that the induction of apoptosis of endocardium and erythrocytes by β-lapachone is mediated through an NQO1- and calcium-dependent pathway.</p> <p>Conclusions</p> <p>The novel finding of this study is that β-lapachone affects heart morphogenesis and function through the induction of apoptosis of endocardium and erythrocytes. In addition, this study further demonstrates the importance of endocardium and hemodynamic forces on heart morphogenesis and contractile performance.</p