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This paper discusses strategies to improve the Gravity Recovery And Climate Experiment (GRACE) monthly solutions computed at the Astronomical Institute of the University of Bern (AIUB) which are contributing to the Horizon 2020 project G3P – Global Gravity-based Groundwater Product. To improve the AIUB-GRACE gravity field solutions, we updated the use of the Level-1B observations, adapted the background models, and improved the processing strategies in terms of instrument screening and parameterization. We used the Release 3 K-band product (KBR) and star camera data (L1B RL03), and we adopted Release 6 of the Atmospheric and Ocean De-aliasing (AOD1B RL06) product. For the accelerometer parameterization, we used arc-wise full scale factor matrix and arc-wise third-order polynomial biases. The new accelerometer parameterization is effective in reducing noise over the oceans in gravity field solutions, especially for the late years of the GRACE mission when the thermal control was switched off. In this paper, we show that the outliers in the KBR antenna offset correction (AOC) are projected into the range rate residuals; therefore, we used the KBR AOC as the main source for outlier detection and eliminated the AOC above a threshold for all data before the gravity field processing. The full time series of GRACE AIUB-G3P gravity field solutions (Darbeheshti et al., 2023b) is available at https://doi.org/10.5880/ICGEM.2023.001.

Gene ontology analyses of high-confidence autism spectrum disorder (ASD) risk genes highlight chromatin regulation and synaptic function as major contributors to pathobiology. Our recent functional work in vivo has additionally implicated tubulin biology and cellular proliferation. As many chromatin regulators, including the ASD risk genes ADNP and CHD3, are known to directly regulate both tubulins and histones, we studied the five chromatin regulators most strongly associated with ASD (ADNP, CHD8, CHD2, POGZ and KMT5B) specifically with respect to tubulin biology. We observe that all five localize to microtubules of the mitotic spindle in vitro in human cells and in vivo in Xenopus. Investigation of CHD2 provides evidence that mutations present in individuals with ASD cause a range of microtubule-related phenotypes, including disrupted localization of the protein at mitotic spindles, cell cycle stalling, DNA damage and cell death. Lastly, we observe that ASD genetic risk is significantly enriched among tubulin-associated proteins, suggesting broader relevance. Together, these results provide additional evidence that the role of tubulin biology and cellular proliferation in ASD warrants further investigation and highlight the pitfalls of relying solely on annotated gene functions in the search for pathological mechanisms., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

Copy number variants (CNVs) associated with neurodevelopmental disorders are characterized by extensive phenotypic heterogeneity. In particular, one CNV was identified in a subset of children clinically diagnosed with intellectual disabilities (ID) that results in a hemizygous deletion of multiple genes at chromosome 16p12.1. In addition to ID, individuals with this deletion display a variety of symptoms including microcephaly, seizures, cardiac defects, and growth retardation. Moreover, patients also manifest severe craniofacial abnormalities, such as micrognathia, cartilage malformation of the ears and nose, and facial asymmetries; however, the function of the genes within the 16p12.1 region have not been studied in the context of vertebrate craniofacial development. The craniofacial tissues affected in patients with this deletion all derive from the same embryonic precursor, the cranial neural crest, leading to the hypothesis that one or more of the 16p12.1 genes may be involved in regulating neural crest cell (NCC)-related processes. To examine this, we characterized the developmental role of the 16p12.1-affected gene orthologs, polr3e , mosmo , uqcrc2 , and cdr2 , during craniofacial morphogenesis in the vertebrate model system, Xenopus laevis . While the currently-known cellular functions of these genes are diverse, we find that they share similar expression patterns along the neural tube, pharyngeal arches, and later craniofacial structures. As these genes show co-expression in the pharyngeal arches where NCCs reside, we sought to elucidate the effect of individual gene depletion on craniofacial development and NCC migration. We find that reduction of several 16p12.1 genes significantly disrupts craniofacial and cartilage formation, pharyngeal arch migration, as well as NCC specification and motility. Thus, we have determined that some of these genes play an essential role during vertebrate craniofacial patterning by regulating specific processes during NCC development, which may be an underlying mechanism contributing to the craniofacial defects associated with the 16p12.1 deletion., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lasser, Bolduc, Murphy, O'Brien, Lee, Girirajan and Lowery.)