Geminin regulates the transcriptional and epigenetic status of neuronal fate-promoting genes during mammalian neurogenesis

Regulating the transition from lineage-restricted progenitors to terminally differentiated cells is a central aspect of nervous system development. Here, we investigated the role of the nucleoprotein geminin in regulating neurogenesis at a mechanistic level during both Xenopus primary neurogenesis and mammalian neuronal differentiation in vitro. The latter work utilized neural cells derived from embryonic stem and embryonal carcinoma cells in vitro and neural stem cells from mouse forebrain. In all of these contexts, geminin antagonized the ability of neural basic helix-loop-helix (bHLH) transcription factors to activate transcriptional programs promoting neurogenesis. Furthermore, geminin promoted a bivalent chromatin state, characterized by the presence of both activating and repressive histone modifications, at genes encoding transcription factors that promote neurogenesis. This epigenetic state restrains the expression of genes that regulate commitment of undifferentiated stem and neuronal precursor cells to neuronal lineages. However, maintaining geminin at high levels was not sufficient to prevent terminal neuronal differentiation. Therefore, these data support a model whereby geminin promotes the neuronal precursor cell state by modulating both the epigenetic status and expression of genes encoding neurogenesis-promoting factors. Additional developmental signals acting in these cells can then control their transition toward terminal neuronal or glial differentiation during mammalian neurogenesis

P6: Predictors of compliance with COVID-19 related non- pharmaceutical interventions amongst university students

College campuses have been an area where the novel coronavirus has spread rapidly, thus this study is focused on compliance with COVID-19 related non-pharmaceutical interventions among college students.We surveyed over 600 college students from across the United States and modeled predictors of compliance with non-pharmaceutical interventions. To determine how applicable nationwide modeling might be to individual local campuses we also administered this same survey to nearly 600 students at two large universities in Utah County (Brigham Young University and Utah Valley University). We then ran structural equation modeling (SEM) to determine what factors are related to student compliance with non-pharmaceutical interventions

Direct detection of Rydberg–Rydberg millimeter-wave transitions in a buffer gas cooled molecular beam

Millimeter-wave transitions between molecular Rydberg states (n ∼ 35) of barium monofluoride are directly detected via Free Induction Decay (FID). Two powerful technologies are used in combination: Chirped-Pulse millimeter-Wave (CPmmW) spectroscopy and a buffer gas cooled molecular beam photoablation source. Hundreds of Rydberg–Rydberg transitions are recorded in 1 h with >10:1 signal:noise ratio and ∼150 kHz resolution. This high resolution, high spectral velocity experiment promises new strategies for rapid measurements of structural and dynamical information, such as the electric structure (multipole moments and polarizabilities) of the molecular ion-core and the strengths and mechanisms of resonances between Rydberg electron and ion-core motions. Direct measurements of Rydberg–Rydberg transitions with kilo-Debye dipole moments support efficient and definitive spectral analysis techniques, such as the Stark demolition and polarization diagnostics, which enable semi-automatic assignments of core-nonpenetrating Rydberg states. In addition, extremely strong radiation-mediated collective effects (superradiance) in a dense Rydberg gas of barium atoms are observed.National Science Foundation (U.S.) (Grant No. CHE-1361865)United States. Department of Defense (National Defence Science & Engineering Graduate Fellowship (NDSEG) Program

Vfr Directly Activates exsA Transcription To Regulate Expression of the Pseudomonas aeruginosa Type III Secretion System

ABSTRACT The Pseudomonas aeruginosa cyclic AMP (cAMP)-Vfr system (CVS) is a global regulator of virulence gene expression. Regulatory targets include type IV pili, secreted proteases, and the type III secretion system (T3SS). The mechanism by which CVS regulates T3SS gene expression remains undefined. Single-cell expression studies previously found that only a portion of the cells within a population express the T3SS under inducing conditions, a property known as bistability. We now report that bistability is altered in a vfr mutant, wherein a substantially smaller fraction of the cells express the T3SS relative to the parental strain. Since bistability usually involves positive-feedback loops, we tested the hypothesis that virulence factor regulator (Vfr) regulates the expression of exsA . ExsA is the central regulator of T3SS gene expression and autoregulates its own expression. Although exsA is the last gene of the exsCEBA polycistronic mRNA, we demonstrate that Vfr directly activates exsA transcription from a second promoter (P exsA ) located immediately upstream of exsA . P exsA promoter activity is entirely Vfr dependent. Direct binding of Vfr to a P exsA promoter probe was demonstrated by electrophoretic mobility shift assays, and DNase I footprinting revealed an area of protection that coincides with a putative Vfr consensus-binding site. Mutagenesis of that site disrupted Vfr binding and P exsA promoter activity. We conclude that Vfr contributes to T3SS gene expression through activation of the P exsA promoter, which is internal to the previously characterized exsCEBA operon. IMPORTANCE Vfr is a cAMP-dependent DNA-binding protein that functions as a global regulator of virulence gene expression in Pseudomonas aeruginosa . Regulation by Vfr allows for the coordinate production of related virulence functions, such as type IV pili and type III secretion, required for adherence to and intoxication of host cells, respectively. Although the molecular mechanism of Vfr regulation has been defined for many target genes, a direct link between Vfr and T3SS gene expression had not been established. In the present study, we report that Vfr directly controls exsA transcription, the master regulator of T3SS gene expression, from a newly identified promoter located immediately upstream of exsA

The deubiquitinase (DUB) USP13 promotes Mcl-1 stabilisation in cervical cancer

Protein ubiquitination is a critical regulator of cellular homeostasis. Aberrations in the addition or removal of ubiquitin can result in the development of cancer and key components of the ubiquitination machinery serve as oncogenes or tumour suppressors. An emerging target in the development of cancer therapeutics are the deubiquitinase (DUB) enzymes that remove ubiquitin from protein substrates. Whether this class of enzyme plays a role in cervical cancer has not been fully explored. By interrogating the cervical cancer data from the TCGA consortium, we noted that the DUB USP13 is amplified in ~15% of cervical cancer cases. We confirmed that USP13 expression was increased in cervical cancer cell lines, cytology samples from patients with cervical disease and in cervical cancer tissue. Depletion of USP13 inhibited cervical cancer cell proliferation. Mechanistically, USP13 bound to, deubiquitinated and stabilised Mcl-1, a pivotal member of the anti-apoptotic BCL-2 family. Furthermore, reduced Mcl-1 expression partially contributed to the observed proliferative defect in USP13 depleted cells. Importantly, the expression of USP13 and Mcl-1 proteins correlated in cervical cancer tissue. Finally, we demonstrated that depletion of USP13 expression or inhibition of USP13 enzymatic activity increased the sensitivity of cervical cancer cells to the BH3 mimetic inhibitor ABT-263. Together, our data demonstrates that USP13 is a potential oncogene in cervical cancer that functions to stabilise the pro-survival protein Mcl-1, offering a potential therapeutic target for these cancers

Concert recording 2013-12-04

[Track 01]. Omaggio / Manuel de Falla -- [Track 02]. Bossa cancao / Frank Basan -- [Track 03]. Spanish study / Frederick Noad -- [Track 04]. Adelita / Francisco Tarrega -- [Track 05]. Everything happens to me / Dennis & Adair -- [Track 06]. 4 on 6 / Wes Montgomery -- [Track 07]. All of me / Simons and Marks -- [Track 08]. Exactly like you / McHugh & Fields -- [Track 09]. Pent up house / Sonny Rollins -- [Track 10]. Ornithology / Charlie Parker -- [Track 11]. Black Orpheus / Luiz Bonfa -- [Track 12]. Bluesette / Toots Thielemans -- [Track 13]. Asturias / Isaac Albeniz

Performance and design evaluation of the RAID-II storage server

RAID-II is a high-bandwidth, network-attached storage server designed and implemented at the University of California at Berkeley. In this paper, we measure the performance of RAID-II and evaluate various architectural decisions made during the design process. We first measure the end-to-end performance of the system to be approximately 20 MB/s for both disk array reads and writes. We then perform a bottleneck analysis by examining the performance of each individual subsystem and conclude that the disk subsystem limits performance. By adding a custom interconnect board with a high-speed memory and bus system and parity engine, we are able to achieve a performance speedup of 8 to 15 over a comparative system using only off-the-shelf hardware.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44815/1/10619_2005_Article_BF01266330.pd