Terracottas in the Mediterranean Through Time II

The international conference Terracottas in the Mediterranean Through Time II will be held at the University of Haifa, Israel, from March 12 to March 15, 2018

Children in Need: Evidence for a Children’s Cult from the Roman Temple of Omrit in Northern Israel

Excavations of the Roman temple at Horvat Omrit, situated in the foothills of Mount Hermon and the Golan, yielded terracotta figurines dated from the first century BC—first century AD. Some 100 fragments of figurines portray young children standing with arms lifted up from the sides and bent at the elbow, palm turned outward. Although this group is unique in its iconography, it fits in with nearby temples in Phoenicia, where numerous figurines and statues of children were consecrated. Images of children from temples around the Mediterranean are often associated with healing cults and rites of passage. The child figurines from Omrit are examined with regard to their gesture, age, and gender, in order to reconstruct the likely cult that took place in the temple. The picture emerging from the terracottas is of family rites celebrating a crucial threshold in life, when passing from infancy to childhood at around the age of three. This is a vulnerable stage in childhood, since mortality rate among young children was very high in ancient societies, and rites were performed to protect them. These rites have further significance in terms of socialization, in introducing the infant to the family, to the cult, and to society in general

DAP-kinase-mediated phosphorylation on the BH3 domain of beclin 1 promotes dissociation of beclin 1 from Bcl-XL and induction of autophagy

Autophagy, an evolutionarily conserved process, has functions both in cytoprotective and programmed cell death mechanisms. Beclin 1, an essential autophagic protein, was recently identified as a BH3-domain-only protein that binds to Bcl-2 anti-apoptotic family members. The dissociation of beclin 1 from its Bcl-2 inhibitors is essential for its autophagic activity, and therefore should be tightly controlled. Here, we show that death-associated protein kinase (DAPK) regulates this process. The activated form of DAPK triggers autophagy in a beclin-1-dependent manner. DAPK phosphorylates beclin 1 on Thr 119 located at a crucial position within its BH3 domain, and thus promotes the dissociation of beclin 1 from Bcl-XL and the induction of autophagy. These results reveal a substrate for DAPK that acts as one of the core proteins of the autophagic machinery, and they provide a new phosphorylation-based mechanism that reduces the interaction of beclin 1 with its inhibitors to activate the autophagic machinery

Automated Evaluation of Human Embryo Blastulation and Implantation Potential using Deep‐Learning

In in vitro fertilization (IVF) treatments, early identification of embryos with high implantation potential is required for shortening time to pregnancy while avoiding clinical complications to the newborn and the mother caused by multiple pregnancies. Current classification tools are based on morphological and morphokinetic parameters that are manually annotated using time‐lapse video files. However, manual annotation introduces interobserver and intraobserver variability and provides a discrete representation of preimplantation development while ignoring dynamic features that are associated with embryo quality. A fully automated and standardized classifiers are developed by training deep neural networks directly on the raw video files of >6200 blastulation‐labeled and >5500 implantation‐labeled embryos. Prediction of embryo implantation is more accurate than the current state‐of‐the‐art morphokientic classifier. Embryo classification improves with video length where the most predictive images show only partial association with morphological features. Deep learning substitute to human evaluation of embryo developmental competence thus contributes to implementing single embryo transfer methodology

From a genome-wide screen of RNAi molecules against SARS-CoV-2 to a validated broad-spectrum and potent prophylaxis.

Funder: Bill and Melinda Gates FoundationExpanding the arsenal of prophylactic approaches against SARS-CoV-2 is of utmost importance, specifically those strategies that are resistant to antigenic drift in Spike. Here, we conducted a screen of over 16,000 RNAi triggers against the SARS-CoV-2 genome, using a massively parallel assay to identify hyper-potent siRNAs. We selected Ten candidates for in vitro validation and found five siRNAs that exhibited hyper-potent activity (IC50 < 20 pM) and strong blockade of infectivity in live-virus experiments. We further enhanced this activity by combinatorial pairing of the siRNA candidates and identified cocktails that were active against multiple types of variants of concern (VOC). We then examined over 2,000 possible mutations in the siRNA target sites by using saturation mutagenesis and confirmed broad protection of the leading cocktail against future variants. Finally, we demonstrated that intranasal administration of this siRNA cocktail effectively attenuates clinical signs and viral measures of disease in the gold-standard Syrian hamster model. Our results pave the way for the development of an additional layer of antiviral prophylaxis that is orthogonal to vaccines and monoclonal antibodies

From a genome-wide screen of RNAi molecules against SARS-CoV-2 to a validated broad-spectrum and potent prophylaxis.

Acknowledgements: This study was funded in part by the Bill & Melinda Gates Foundation and by the intramural program of the National Institutes of Health. The findings and conclusions contained within are those of the authors and do not necessarily reflect positions or policies of the Bill & Melinda Gates Foundation. This work was conducted in part under CRADA 2020-0597 between the VRC/NIAID and Eleven Therapeutics. Some of the work was funded by research grants to I.G. from Wellcome Trust, reference no. 207498/Z/17/Z and MRC/UKRI G2P-UK National Virology consortium, reference no. MR/W005611/1. I.G. is a Wellcome Trust Senior Fellow.Funder: Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation); doi: https://doi.org/10.13039/100000865Expanding the arsenal of prophylactic approaches against SARS-CoV-2 is of utmost importance, specifically those strategies that are resistant to antigenic drift in Spike. Here, we conducted a screen of over 16,000 RNAi triggers against the SARS-CoV-2 genome, using a massively parallel assay to identify hyper-potent siRNAs. We selected Ten candidates for in vitro validation and found five siRNAs that exhibited hyper-potent activity (IC50 < 20 pM) and strong blockade of infectivity in live-virus experiments. We further enhanced this activity by combinatorial pairing of the siRNA candidates and identified cocktails that were active against multiple types of variants of concern (VOC). We then examined over 2,000 possible mutations in the siRNA target sites by using saturation mutagenesis and confirmed broad protection of the leading cocktail against future variants. Finally, we demonstrated that intranasal administration of this siRNA cocktail effectively attenuates clinical signs and viral measures of disease in the gold-standard Syrian hamster model. Our results pave the way for the development of an additional layer of antiviral prophylaxis that is orthogonal to vaccines and monoclonal antibodies