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dCas9-based epigenome editing suggests acquisition of histone methylation is not sufficient for target gene repression.
Distinct epigenomic profiles of histone marks have been associated with gene expression, but questions regarding the causal relationship remain. Here we investigated the activity of a broad collection of genomically targeted epigenetic regulators that could write epigenetic marks associated with a repressed chromatin state (G9A, SUV39H1, Krüppel-associated box (KRAB), DNMT3A as well as the first targetable versions of Ezh2 and Friend of GATA-1 (FOG1)). dCas9 fusions produced target gene repression over a range of 0- to 10-fold that varied by locus and cell type. dCpf1 fusions were unable to repress gene expression. The most persistent gene repression required the action of several effector domains; however, KRAB-dCas9 did not contribute to persistence in contrast to previous reports. A 'direct tethering' strategy attaching the Ezh2 methyltransferase enzyme to dCas9, as well as a 'recruitment' strategy attaching the N-terminal 45 residues of FOG1 to dCas9 to recruit the endogenous nucleosome remodeling and deacetylase complex, were both successful in targeted deposition of H3K27me3. Surprisingly, however, repression was not correlated with deposition of either H3K9me3 or H3K27me3. Our results suggest that so-called repressive histone modifications are not sufficient for gene repression. The easily programmable dCas9 toolkit allowed precise control of epigenetic information and dissection of the relationship between the epigenome and gene regulation
Competitive Exclusion in a DAE Model for Microbial Electrolysis Cells
Microbial electrolysis cells (MECs) employ electroactive bacteria to perform
extracellular electron transfer, enabling hydrogen generation from
biodegradable substrates. In previous work, we developed and analyzed a
differential-algebraic equation (DAE) model for MECs. The model resembles a
chemostat with ordinary differential equations (ODEs) for concentrations of
substrate, microorganisms, and an extracellular mediator involved in electron
transfer. There is also an algebraic constraint for electric current and
hydrogen production. Our goal is to determine the outcome of competition
between methanogenic archaea and electroactive bacteria, because only the
latter contribute to electric current and resulting hydrogen production. We
investigate asymptotic stability in two industrially relevant versions of the
model. An important aspect of chemostats models is the principle of competitive
exclusion -- only microbes which grow at the lowest substrate concentration
will survive as . We show that if methanogens grow at the lowest
substrate concentration, then the equilibrium corresponding to competitive
exclusion by methanogens is globally asymptotically stable. The analogous
result for electroactive bacteria is not necessarily true. We show that local
asymptotic stability of exclusion by electroactive bacteria is not guaranteed,
even in a simplified version of the model. In this case, even if electroactive
bacteria can grow at the lowest substrate concentration, a few additional
conditions are required to guarantee local asymptotic stability. We also
provide numerical simulations supporting these arguments. Our results suggest
operating conditions that are most conducive to success of electroactive
bacteria and the resulting current and hydrogen production in MECs. This will
help identify when methane production or electricity and hydrogen production
are favored
Terahertz Time-Domain Magnetospectroscopy of a High-Mobility Two-Dimensional Electron Gas
We have observed cyclotron resonance in a high-mobility GaAs/AlGaAs
two-dimensional electron gas by using the techniques of terahertz time-domain
spectroscopy combined with magnetic fields. From this, we calculate the real
and imaginary parts of the diagonal elements of the magnetoconductivity tensor,
which in turn allows us to extract the concentration, effective mass, and
scattering time of the electrons in the sample. We demonstrate the utility of
ultrafast terahertz spectroscopy, which can recover the true linewidth of
cyclotron resonance in a high-mobility () sample without being affected by the saturation effect.Comment: 4 pages, 3 figure
High frequency impedance based fault location in distribution system with DGs
Distributed Generations (DGs) with power electronic devices and their control loops will cause distortion to the fault currents and result in errors for power frequency measurement based fault locations. This might jeopardize the distribution system fault restoration and reduce the grid resilience. The proposed method uses high frequency (up to 3kHz) fault information and short window measurement to avoid the influence of DG control loops. Applying the DG high frequency impedance model, faults can be accurately located by measuring the system high frequency line reactance. Assisted with the DG side recorded unsynchronized data, this method can be employed to distribution systems with multiple branches and laterals
Can antiferromagnetism and superconductivity coexist in the high-field paramagnetic superconductor Nd(O,F)FeAs?
We present measurements of the temperature and field dependencies of the
magnetization M(T,H) of Nd(O0.89F0.11)FeAs at fields up to 33T, which show that
superconductivity with the critical temperature Tc ~ 51K cannot coexist with
antiferromagnetic ordering. Although M(T,H) at 55 < T < 140K exhibits a clear
Curie-Weiss temperature dependence corresponding to the Neel temperature TN ~
11-12K, the behavior of M(T,H) below Tc is only consistent with either
paramagnetism of weakly interacting magnetic moments or a spin glass state. We
suggest that the anomalous magnetic behavior of an unusual high-field
paramagnetic superconductor Nd(O1-xFx)FeAs is mostly determined by the magnetic
Nd ions.Comment: 4 pages, 4 figure
CatSper and Two-Pore channels (TPC) in GtoPdb v.2022.1
CatSper channels (CatSper1-4, nomenclature as agreed by NC-IUPHAR [14]) are putative 6TM, voltage-gated, alkalinization-activated calcium permeant channels that are presumed to assemble as a tetramer of α-like subunits and mediate the current ICatSper [23]. In mammals, CatSper subunits are structurally most closely related to individual domains of voltage-activated calcium channels (Cav) [40]. CatSper1 [40], CatSper2 [37] and CatSpers 3 and 4 [27, 21, 36], in common with a putative 2TM auxiliary CatSperβ protein [26] and two putative 1TM associated CatSperγ and CatSperδ proteins [46, 12], are restricted to the testis and localised to the principle piece of sperm tail. The novel cross-species CatSper channel inhibitor, RU1968, has been proposed as a useful tool to aid characterisation of native CatSper channels [41].Two-pore channels (TPCs) are structurally related to CatSpers, CaVs and NaVs. TPCs have a 2x6TM structure with twice the number of TMs of CatSpers and half that of CaVs. There are three animal TPCs (TPC1-TPC3). Humans have TPC1 and TPC2, but not TPC3. TPC1 and TPC2 are localized in endosomes and lysosomes [5]. TPC3 is also found on the plasma membrane and forms a voltage-activated, non-inactivating Na+ channel [6]. All the three TPCs are Na+-selective under whole-cell or whole-organelle patch clamp recording [48, 8, 7]. The channels may also conduct Ca2+ [31]
Pancreatic islet cell therapy for type I diabetes: understanding the effects of glucose stimulation on islets in order to produce better islets for transplantation
While insulin replacement remains the cornerstone treatment for type I diabetes mellitus (T1DM), the transplantation of pancreatic islets of Langerhans has the potential to become an important alternative. And yet, islet transplant therapy is limited by several factors, including far too few donor pancreases. Attempts to expand mature islets or to produce islets from stem cells are far from clinical application. The production and expansion of the insulin-producing cells within the islet (so called β cells), or even creating cells that secrete insulin under appropriate physiological control, has proven difficult. The difficulty is explained, in part, because insulin synthesis and release is complex, unique, and not entirely characterized. Understanding β-cell function at the molecular level will likely facilitate the development of techniques to manufacture β-cells from stem cells. We will review islet transplantation, as well as the mechanisms underlying insulin transcription, translation and glucose stimulated insulin release
MicroRNA and gene expression patterns in the differentiation of human embryonic stem cells
<p>Abstract</p> <p>Background</p> <p>The unique features of human embryonic stem (hES) cells make them the best candidate resource for both cell replacement therapy and development research. However, the molecular mechanisms responsible for the simultaneous maintenance of their self-renewal properties and undifferentiated state remain unclear. Non-coding microRNAs (miRNA) which regulate mRNA cleavage and inhibit encoded protein translation exhibit temporal or tissue-specific expression patterns and they play an important role in development timing.</p> <p>Results</p> <p>In this study, we analyzed miRNA and gene expression profiles among samples from 3 hES cell lines (H9, I6 and BG01v), differentiated embryoid bodies (EB) derived from H9 cells at different time points, and 5 adult cell types including Human Microvascular Endothelial Cells (HMVEC), Human Umbilical Vein Endothelial Cells (HUVEC), Umbilical Artery Smooth Muscle Cells (UASMC), Normal Human Astrocytes (NHA), and Lung Fibroblasts (LFB). This analysis rendered 104 miRNAs and 776 genes differentially expressed among the three cell types. Selected differentially expressed miRNAs and genes were further validated and confirmed by quantitative real-time-PCR (qRT-PCR). Especially, members of the miR-302 cluster on chromosome 4 and miR-520 cluster on chromosome 19 were highly expressed in undifferentiated hES cells. MiRNAs in these two clusters displayed similar expression levels. The members of these two clusters share a consensus 7-mer seed sequence and their targeted genes had overlapping functions. Among the targeted genes, genes with chromatin structure modification function are enriched suggesting a role in the maintenance of chromatin structure. We also found that the expression level of members of the two clusters, miR-520b and miR-302c, were negatively correlated with their targeted genes based on gene expression analysis</p> <p>Conclusion</p> <p>We identified the expression patterns of miRNAs and gene transcripts in the undifferentiation of human embryonic stem cells; among the miRNAs that are highly expressed in undifferentiated embryonic stem cells, the miR-520 cluster may be closely involved in hES cell function and its relevance to chromatin structure warrants further study.</p
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