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Differentiation therapy induces the maturation and clearance of acute myeloid leukemia cells. Here, using a mouse model, the authors show that a specific lineage of mature leukemia-derived cells persists during remission and is responsible for disease relapse.

In addition to their roles in hemostasis and thrombosis, platelets are now recognized as making important contributions to a wide variety of inflammatory responses. This function primarily occurs as a result of intravascular interactions of platelets with leukocytes undergoing recruitment to the site of inflammation. As these interactions occur under the shear forces of flowing blood, they are typically rapid and highly dynamic. As such, the use of rapid frame-rate forms of in vivo microscopy, such as spinning-disk confocal intravital microscopy, have emerged as the optimal approaches for investigating these interactions and delineating their molecular basis and contribution to the inflammatory response. In this review, we provide an overview of the different methodologies employed to image platelet–leukocyte interactions in vivo, and examine the contributions of these interactions to inflammation that have been uncovered by intravital imaging.

Chemotaxis is a major driver of cancer spread, but in most cases we do not know where gradients of attractant come from. In the case of melanoma, chemotaxis to LPA is an important driver of metastasis, and the gradients are made by the tumour cells themselves, by locally breaking down ambient LPA. We have now made a general assay for self-generated chemotaxis, and used it to show that the enzyme LPP3 is responsible for breaking down LPA and thus creating the gradients. Further analysis shows LPP3 is important in several invasion assays, in particular 3D ones in which cells spread outwards through matrix. The new assays will illuminate where physiological self-generated gradients occur; we believe they will be common throughout biology and pathology.

The high mortality of melanoma is caused by rapid spread of cancer cells, which occurs unusually early in tumour evolution. Unlike most solid tumours, thickness rather than cytological markers or differentiation is the best guide to metastatic potential. Multiple stimuli that drive melanoma cell migration have been described, but it is not clear which are responsible for invasion, nor if chemotactic gradients exist in real tumours. In a chamber-based assay for melanoma dispersal, we find that cells migrate efficiently away from one another, even in initially homogeneous medium. This dispersal is driven by positive chemotaxis rather than chemorepulsion or contact inhibition. The principal chemoattractant, unexpectedly active across all tumour stages, is the lipid agonist lysophosphatidic acid (LPA) acting through the LPA receptor LPAR1. LPA induces chemotaxis of remarkable accuracy, and is both necessary and sufficient for chemotaxis and invasion in 2-D and 3-D assays. Growth factors, often described as tumour attractants, cause negligible chemotaxis themselves, but potentiate chemotaxis to LPA. Cells rapidly break down LPA present at substantial levels in culture medium and normal skin to generate outward-facing gradients. We measure LPA gradients across the margins of melanomas in vivo, confirming the physiological importance of our results. We conclude that LPA chemotaxis provides a strong drive for melanoma cells to invade outwards. Cells create their own gradients by acting as a sink, breaking down locally present LPA, and thus forming a gradient that is low in the tumour and high in the surrounding areas. The key step is not acquisition of sensitivity to the chemoattractant, but rather the tumour growing to break down enough LPA to form a gradient. Thus the stimulus that drives cell dispersal is not the presence of LPA itself, but the self-generated, outward-directed gradient.

This research aims to analyze Artificial Insemination Children’s Standing anddiscover Their Hereditary Right from a Deceased Father viewed in Indonesia’sPositive Law. Judgment will affect to whether artificial insemination from the deceasedhusband’s sperm can be performed or not. Further, the judgment that decidethe artificial insemination can be performed will affect children’s standing from adeceased father. If the children are born alive, then the standing is legal based on Article 250 of Civil Code, Islamic Law (Sharia law), and customary law. In addition,customary law claims the standing as adopt them on culture. Artificial inseminationchildren’s hereditary right from a deceased father has the right to inherit (asheir). How to cite item: Susanto, C., Siti Hamidah, S., Rachmi Sulistyarini, R. (2020). Kedudukan hukum dan hak waris anak hasil inseminasi buatan dari ayah yang telah meninggal. Jurnal Cakrawala Hukum, 11(3). 302-312.doi:10.26905/idjch.v11i3.5475.