INPP5E Preserves Genomic Stability through Regulation of Mitosis

The partially understood phosphoinositide signaling cascade regulates multiple aspects of cellular metabolism. Previous studies revealed that INPP5E, the inositol polyphosphate-5-phosphatase that is mutated in the developmental disorders Joubert and MORM syndromes, is essential for the function of the primary cilium and maintenance of phosphoinositide balance in nondividing cells. Here, we report that INPP5E further contributes to cellular homeostasis by regulating cell division. We found that silencing or genetic knockout of INPP5E in human and murine cells impairs the spindle assembly checkpoint, centrosome and spindle function, and maintenance of chromosomal integrity. Consistent with a cell cycle regulatory role, we found that INPP5E expression is cell cycle dependent, peaking at mitotic entry. INPP5E localizes to centrosomes, chromosomes, and kinetochores in early mitosis and shuttles to the midzone spindle at mitotic exit. Our findings identify the previously unknown, essential role of INPP5E in mitosis and prevention of aneuploidy, providing a new perspective on the function of this phosphoinositide phosphatase in health and development

Obesity control by SHIP inhibition requires pan-paralog inhibition and an intact eosinophil compartment

peer reviewedHere we extend the understanding of how chemical inhibition of SHIP paralogs controls obesity. We compare different classes of SHIP inhibitors and find that selective inhibitors of SHIP1 or SHIP2 are unable to prevent weight gain and body fat accumulation during increased caloric intake. Surprisingly, only pan-SHIP1/2 inhibitors (pan-SHIPi) prevent diet-induced obesity. We confirm that pan-SHIPi is essential by showing that dual treatment with SHIP1 and SHIP2 selective inhibitors reduced adiposity during excess caloric intake. Consistent with this, genetic inactivation of both SHIP paralogs in eosinophils or myeloid cells also reduces obesity and adiposity. In fact, pan-SHIPi requires an eosinophil compartment to prevent diet-induced adiposity, demonstrating that pan-SHIPi acts via an immune mechanism. We also find that pan-SHIPi increases ILC2 cell function in aged, obese mice to reduce their obesity. Finally, we show that pan-SHIPi also reduces hyperglycemia, but not via eosinophils, indicating a separate mechanism for glucose control

Shape Variation in Aterian Tanged Tools and the Origins of Projectile Technology: A Morphometric Perspective on Stone Tool Function

BACKGROUND: Recent findings suggest that the North African Middle Stone Age technocomplex known as the Aterian is both much older than previously assumed, and certainly associated with fossils exhibiting anatomically modern human morphology and behavior. The Aterian is defined by the presence of 'tanged' or 'stemmed' tools, which have been widely assumed to be among the earliest projectile weapon tips. The present study systematically investigates morphological variation in a large sample of Aterian tools to test the hypothesis that these tools were hafted and/or used as projectile weapons. METHODOLOGY/PRINCIPAL FINDINGS: Both classical morphometrics and Elliptical Fourier Analysis of tool outlines are used to show that the shape variation in the sample exhibits size-dependent patterns consistent with a reduction of the tools from the tip down, with the tang remaining intact. Additionally, the process of reduction led to increasing side-to-side asymmetries as the tools got smaller. Finally, a comparison of shape-change trajectories between Aterian tools and Late Paleolithic arrowheads from the North German site of Stellmoor reveal significant differences in terms of the amount and location of the variation. CONCLUSIONS/SIGNIFICANCE: The patterns of size-dependent shape variation strongly support the functional hypothesis of Aterian tools as hafted knives or scrapers with alternating active edges, rather than as weapon tips. Nevertheless, the same morphological patterns are interpreted as one of the earliest evidences for a hafting modification, and for the successful combination of different raw materials (haft and stone tip) into one implement, in itself an important achievement in the evolution of hominin technologies

Opgravingen in Maasbree-Siberië : een grafveld uit de Romeinse tijd en bewoning uit de late prehistorie en Vroege Middeleeuwen

Met lit.opg., bijl

Plangebied Sittard-het Groene Net - deelgebied Da Capo, gemeente Sittard-Geleen; archeologische opgraving - variant archeologische begeleiding.

In opdracht van Het Groene Net heeft RAAP van 2 mei 2019 tot en met 3 mei 2019 een archeologische opgraving - variant archeologische begeleiding uitgevoerd in het kader van het project ‘Sittard-Het Groene Net - deelgebied Da Capo’ in de gemeente Sittard-Geleen. Het doel van de begeleiding was het vaststellen van de archeologische waarde van het terrein. Omdat het onderzoeksgebied verhard is was regulier archeologische onderzoek voorafgaand aan de geplande ontwikkeling niet mogelijk. Het archeologisch onderzoek is daarom gecombineerd met de civieltechnische werkzaamheden en uitgevoerd als een opgraving - variant archeologische begeleiding. Tijdens het onderzoek zijn de ondergrondse civiele werkzaamheden archeologisch begeleid. In totaal is hierbij een oppervlakte van 497 m² onderzocht. Tijdens het onderzoek zijn geen relevante archeologische resten aangetroffen. Het archeologisch onderzoek binnen het plangebied is afgerond. Er gelden dan ook geen verdere aanbevelingen binnen het onderhavige plangebied