KAT-Independent Gene Regulation by Tip60 Promotes ESC Self-Renewal but Not Pluripotency

Although histone-modifying enzymes are generally assumed to function in a manner dependent on their enzymatic activities, this assumption remains untested for many factors. Here, we show that the Tip60 (Kat5) lysine acetyltransferase (KAT), which is essential for embryonic stem cell (ESC) self-renewal and pre-implantation development, performs these functions independently of its KAT activity. Unlike ESCs depleted of Tip60, KAT-deficient ESCs exhibited minimal alterations in gene expression, chromatin accessibility at Tip60 binding sites, and self-renewal, thus demonstrating a critical KAT-independent role of Tip60 in ESC maintenance. In contrast, KAT-deficient ESCs exhibited impaired differentiation into mesoderm and endoderm, demonstrating a KAT-dependent function in differentiation. Consistent with this phenotype, KAT-deficient mouse embryos exhibited post-implantation developmental defects. These findings establish separable KAT-dependent and KAT-independent functions of Tip60 in ESCs and during differentiation, revealing a complex repertoire of regulatory functions for this essential chromatin remodeling complex

Arf4 is required for Mammalian development but dispensable for ciliary assembly

The primary cilium is a sensory organelle, defects in which cause a wide range of human diseases including retinal degeneration, polycystic kidney disease and birth defects. The sensory functions of cilia require specific receptors to be targeted to the ciliary subdomain of the plasma membrane. Arf4 has been proposed to sort cargo destined for the cilium at the Golgi complex and deemed a key regulator of ciliary protein trafficking. In this work, we show that Arf4 binds to the ciliary targeting sequence (CTS) of fibrocystin. Knockdown of Arf4 indicates that it is not absolutely required for trafficking of the fibrocystin CTS to cilia as steady-state CTS levels are unaffected. However, we did observe a delay in delivery of newly synthesized CTS from the Golgi complex to the cilium when Arf4 was reduced. Arf4 mutant mice are embryonic lethal and die at mid-gestation shortly after node formation. Nodal cilia appeared normal and functioned properly to break left-right symmetry in Arf4 mutant embryos. At this stage of development Arf4 expression is highest in the visceral endoderm but we did not detect cilia on these cells. In the visceral endoderm, the lack of Arf4 caused defects in cell structure and apical protein localization. This work suggests that while Arf4 is not required for ciliary assembly, it is important for the efficient transport of fibrocystin to cilia, and also plays critical roles in non-ciliary processes

The Large Aperture GRB Observatory

The Large Aperture GRB Observatory (LAGO) is aiming at the detection of the high energy (around 100 GeV) component of Gamma Ray Bursts, using the single particle technique in arrays of Water Cherenkov Detectors (WCD) in high mountain sites (Chacaltaya, Bolivia, 5300 m a.s.l., Pico Espejo, Venezuela, 4750 m a.s.l., Sierra Negra, Mexico, 4650 m a.s.l). WCD at high altitude offer a unique possibility of detecting low gamma fluxes in the 10 GeV - 1 TeV range. The status of the Observatory and data collected from 2007 to date will be presented.Comment: 4 pages, proceeding of 31st ICRC 200

Water Cherenkov Detectors response to a Gamma Ray Burst in the Large Aperture GRB Observatory

In order to characterise the behaviour of Water Cherenkov Detectors (WCD) under a sudden increase of 1 GeV - 1 TeV background photons from a Gamma Ray Burst (GRB), simulations were conducted and compared to data acquired by the WCD of the Large Aperture GRB Observatory (LAGO). The LAGO operates arrays of WCD at high altitude to detect GRBs using the single particle technique. The LAGO sensitivity to GRBs is derived from the reported simulations of the gamma initiated particle showers in the atmosphere and the WCD response to secondaries.Comment: 5 pages, proceeding of the 31st ICRC 200

At the southeast fringe of the Bantu expansion: genetic diversity and phylogenetic relationships to other sub-Saharan tribes

Here, we present 12 loci paternal haplotypes (Y-STR profiles) against the backdrop of the Y-SNP marker system of Bantu males from the Maputo Province of Southeast Africa, a region believed to represent the southeastern fringe of the Bantu expansion. Our Maputo Bantu group was analyzed within the context of 27 geographically relevant reference populations in order to ascertain its genetic relationship to other Bantu and non Bantu (Pygmy, Khoisan and Nilotic) sub-equatorial tribes from West and East Africa. This study entails statistical pair wise comparisons and multidimensional scaling based on YSTR Rst distances, network analyses of Bantu (B2a-M150) and Pygmy (B2b-M112) lineages as well as an assessment of Y-SNP distribution patterns. Several notable findings include the following: 1) the Maputo Province Bantu exhibits a relatively close paternal affinity with both east and west Bantu tribes due to high proportion of Bantu Y chromosomal markers, 2) only traces of Khoisan (1.3%) and Pygmy (1.3%) markers persist in the Maputo Province Bantu gene pool, 3) the occurrence of R1a1a-M17/M198, a member of the Eurasian R1a-M420 branch in the population of the Maputo Province, may represent back migration events and/or recent admixture events, 4) the shared presence of E1b1b1-M35 in all Tanzanian tribes examined, including Bantu and non-Bantu groups, in conjunction with its nearly complete absence in the West African populations indicate that, in addition to a shared linguistic, cultural and genetic heritage, geography (e.g., east vs. west) may have impacted the paternal landscape of sub-Saharan Africa, 5) the admixture and assimilation processes of Bantu elements were both highly complex and region-specific

Typical 22q11.2 deletion syndrome appears to confer a reduced risk of schwannoma

Purpose: The LZTR1 gene has been associated with schwannomatosis tumor predisposition and is located in a region that is deleted in the great majority (89%) of patients with 22q11.2 deletion syndrome (22q11.2DS). Since it is known that approximately 1 in 500 people in the general population will develop a sporadic schwannoma and there are no reports of the occurrence of schwannoma in 22q11.2DS, we investigated whether whole-gene deletion of LZTR1 occurs in schwannomatosis and assessed the risk of schwannoma in 22q11.2DS. Methods: We assessed the genetic testing results for LZTR1-associated schwannomatosis and the clinical phenotypes of patients with 22q11.2DS. Results: There were no reports of schwannoma in over 1,500 patients with 22q11.2DS. In addition, no patients meeting clinical diagnostic criteria for schwannomatosis had a whole-gene deletion in LZTR1. Only 1 patient in 110 with an apparently sporadic vestibular schwannoma had a constitutional whole-gene deletion of LZTR1. Conclusion: People with a large 22q11.2 deletion may have a reduced risk of developing a schwannoma compared to the general population

Investigation of network-based information system model

The objective of the DOE-LBNL summer student research program in computer and information sciences focused on investigating database- based http-based information architectures, and implementation of a prototype using DOE`s Comprehensive Epidemiologic Data Resource (CEDR) metadata or Epidemiology Guide content. We were successful in identifying the components of such an information system, and appropriate configuration given the requirements, and in implementing a prototype. This work comprised investigation of various information systems architectures or variants, evaluation and selection of various tools, products, and packages, preparation of databases, database content, output formats, and graphical (World Wide Web- compatible) interfaces. We successfully prepared and demonstrated network access to content from both the CEDR structured documentation and from the DOD Epidemiology Guides (site archive records)

Treatments used for obsessive-compulsive disorder-An international perspective

© 2019 John Wiley & Sons, Ltd.OBJECTIVE: The objective of this study was to characterise international trends in the use of psychotropic medication, psychological therapies, and novel therapies used to treat obsessive-compulsive disorder (OCD). METHODS: Researchers in the field of OCD were invited to contribute summary statistics on the characteristics of their samples. Consistency of summary statistics across countries was evaluated. RESULTS: The study surveyed 19 expert centres from 15 countries (Argentina, Australia, Brazil, China, Germany, Greece, India, Italy, Japan, Mexico, Portugal, South Africa, Spain, the United Kingdom, and the United States) providing a total sample of 7,340 participants. Fluoxetine (n = 972; 13.2%) and fluvoxamine (n = 913; 12.4%) were the most commonly used selective serotonin reuptake inhibitor medications. Risperidone (n = 428; 7.3%) and aripiprazole (n = 415; 7.1%) were the most commonly used antipsychotic agents. Neurostimulation techniques such as transcranial magnetic stimulation, deep brain stimulation, gamma knife surgery, and psychosurgery were used in less than 1% of the sample. There was significant variation in the use and accessibility of exposure and response prevention for OCD. CONCLUSIONS: The variation between countries in treatments used for OCD needs further evaluation. Exposure and response prevention is not used as frequently as guidelines suggest and appears difficult to access in most countries. Updated treatment guidelines are recommended.Peer reviewe