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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2007.12.011 Byline: Takayoshi Inoue (a)(b), Yukiko U. Inoue (a), Junko Asami (a), Hitomi Izumi (a), Shun Nakamura (a), Robb Krumlauf (b) Keywords: Cdh6 (cadherin-6); Mouse; Gene regulation; BAC; Transposon; Homologous recombination; Forebrain; Hindbrain; Compartment; Neural crest cells Abstract: Classic cadherins are cell adhesion molecules whose expression patterns are dynamically modulated in association with their diverse functions during morphogenesis. The large size and complexity of cadherin loci have made it a challenge to investigate the organization of cis-regulatory modules that control their spatiotemporal patterns of expression. Towards this end, we utilized bacterial artificial chromosomes (BACs) containing the Cdh6 gene, a mouse type II classic cadherin, to systematically identify cis-regulatory modules that govern its expression. By inserting a lacZ reporter gene into the Cdh6 BAC and generating a series of modified variants via homologous recombination or transposon insertions that have been examined in transgenic mice, we identified an array of genomic regions that contribute to specific regulation of the gene. These regions span [approximately equal to]350 kb of the locus between 161-kb upstream and 186-kb downstream of the Cdh6 transcription start site. Distinct modules independently regulate compartmental expression (i.e. forebrain, hindbrain rhombomeres, and spinal cord) and/or cell lineage-specific expression patterns (i.e. neural crest subpopulations such as Schwann cells) of Cdh6 at the early developmental stages. With respect to regulation of expression in neural crest cells, we have found that distinct regions contribute to different aspects of expression and have identified a short 79-bp region that is implicated in regulating expression in cells once they have emigrated from the neural tube. These results build a picture of the complex organization of Cdh6 cis-regulatory modules and highlight the diverse inputs that contribute to its dynamic expression during early mouse embryonic development. Author Affiliation: (a) Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Ogawahigashi 4-1-1, Kodaira, Tokyo 187-8502, Japan (b) Stowers Institute for Medical Research, 1000 East, 50th Street, Kansas City, MO 64110, USA Article History: Received 29 June 2007; Revised 5 November 2007; Accepted 9 December 2007

A control method is described to charge seriesconnected ultraelectric double-layer capacitors (ultra-EDLCs) suitable for photovoltaic generation systems in combination with a maximum power point tracking (MPPT) control method. The EDLC charge control method allows the maximum power acquired by the MPPT control to be quickly charged into seriesconnected ultra-EDLCs no matter how the weather conditions may change. In the MPPT control, the output current of the solar arrays is controlled so that the output power converges on the maximum power in the prediction line previously determined based on the linearity between the maximum output power and the optimization current. The proportionality coefficient of the prediction line is automatically corrected using the hill-climbing method when the panel temperature of the solar arrays is changed. The EDLC charge control is performed with the three charge modes, i.e., the constant current charge mode, constant power charge mode, and the constant voltage charge mode while supervising the maximum voltage and allowable temperature of each series-connected EDLC. Effectiveness of the methods is verified by simulations and experiments. Index Terms--Maximum power point tracking (MPPT), photovoltaic (PV), power supply, ultraelectric double-layer capacitors (ultra-EDLCs).

This paper describes a method for maximum power point tracking (MPPT) control while searching for optimal parameters corresponding to weather conditions at that time. The conventional method has problems in that it is impossible to quickly acquire the generation power at the maximum power (MP) point in low solar radiation (irradiation) regions. It is found theoretically and experimentally that the maximum output power and the optimal current, which give this maximum, have a linear relation at a constant temperature. Furthermore, it is also shown that linearity exists between the short-circuit current and the optimal current. MPPT control rules are created based on the findings from solar arrays that can respond at high speeds to variations in irradiation. The proposed MPPT control method sets the output current track on the line that gives the relation between the MP and the optimal current so as to acquire the MP that can be generated at that time by dividing the power and current characteristics into two fields. The method is based on the generated power being a binary function of the output current. Considering the experimental fact that linearity is maintained only at low irradiation below half the maximum irradiation, the proportionality coefficient (voltage coefficient) is compensated for only in regions with more than half the rated optimal current, which correspond to the maximum irradiation. At high irradiation, the voltage coefficient needed to perform the proposed MPPT control is acquired through the hill-climbing method. The effectiveness of the proposed method is verified through experiments under various weather conditions. Index Terms--Current control, irradiation, maximum power point tracking (MPPT), photovoltaic (PV), PV power generation.

Background: Repressor element 1‐silencing transcription factor (REST) is a master regulator that is highly expressed in multipotent stem cells to repress gene networks involving a wide range of biological processes. A recent study has suggested that REST might be involved in a misregulation of its target genes in the embryonic brain of offspring derived from aged fathers. However, detailed analyses of the REST function in spermatogenesis are lacking due to difficulty in the detection of REST protein in specific cell types. Results: To determine localization of REST, we generated an epitope tag knock‐in (KI) mouse line with the C‐terminus insertion of a podoplanin (PA)‐tag at an endogenous Rest locus by the CRISPR/Cas9 system. Localization of the PA‐tag was confirmed in neural stem cells marked with Pax6 in the embryonic brain. Moreover, PA‐tagged REST was detected in undifferentiated and differentiating spermatogonia as well as Sertoli cells in both neonatal and adult testes. Conclusions: We demonstrate that REST is expressed at the early step of spermatogenesis and suggest a possibility that REST may modulate the epigenetic state of male germline cells. Our KI mice may be useful for studying REST‐associated molecular mechanisms of neurodevelopmental and age‐related disorders. Key Findings: PA‐tagging strategy successfully reveals the tissue localization of full‐length REST protein.In the developing testis, REST protein is detected in most of the undifferentiated (PLZF‐positive) and differentiating (KIT‐positive) spermatogonia and in a fraction of Sertoli cells.In the adult testis, the expression of REST in KIT‐positive spermatogonia decreases compared to the developing testis, while the expression in PLZF‐positive spermatogonia is retained to a similar extent.PA‐tagging strategy successfully reveals the tissue localization of full‐length REST protein. [ABSTRACT FROM AUTHOR]

Objective To establish the efficacy of medications, incidence of adverse events (AEs), and withdrawal rates associated with the pharmacological management of chronic spinal cord injury pain. Methodology PubMed, MEDLINE, Embase, CINAHL, Web of Science, CENTRAL, and PsycINFO were searched (November 2017) and updated (January 2020). Two independent review authors screened and identified papers for inclusion. Results Twenty-one studies met inclusion requirements for efficacy analysis and 17 for AE and withdrawal rate analysis; no additional papers were included from the updated 2020 search. Treatments were divided into six categories: anticonvulsants (n = 6), antidepressants (n = 3), analgesics (n = 8), anti-spasticity medications (n = 2), cannabinoids (n = 1), and other (n = 2). Trials of anticonvulsants, antidepressants, and cannabinoids included long-term follow-up trials (2 weeks to 4 months), and trials of analgesics and anti-spasticity medications, among others, were short-term trials (0–2 days). Effectiveness for neuropathic pain was found for pregabalin (3/3 studies) and lidocaine (2/3 studies). Studies using ketamine also reported effectiveness (2/2), but the quality of these papers was rated as poor. The most frequently reported AEs included dizziness, dry mouth, nausea, and constipation. Pregabalin was associated with a higher risk of somnolence (risk ratio [RR] 3.15, 95% confidence interval [CI]: 2.00–4.98) and dizziness (RR 2.9, 95% CI: 1.58–5.30). Ketamine was associated with a higher risk of reduced vision (RR 9.00, 95% CI: 0.05–146.11), dizziness (RR 8.33, 95% CI: 1.73–40.10), and somnolence (RR 7.00, 95% CI: 1.73–40.1). Withdrawal rates ranged from 18.4% for antidepressants to 0–30% for anticonvulsants, 0–10% for anti-spasticity medications, 0–48% for analgesics, 28.6% for cannabinoids, and 0–22.2% for other medications. Conclusion Pregabalin was found to be effective for neuropathic pain vs placebo. Cannabinoids were ineffective for neuropathic pain. AEs are a common cause for withdrawal. The nature of AEs was poorly reported, and AE reporting should be improved in future randomized controlled trials. [ABSTRACT FROM AUTHOR]

Sensitive skin is a condition characterized by hypersensitivity to environmental stimuli, and its pathophysiology has not been fully elucidated. Questionnaires based on subjective symptoms, intervention tests, and measuring devices are used to diagnose sensitive skin; however, objective evaluation methods, including biomarkers, remain to be established. This study aimed to investigate the molecular profiles of self‐reported sensitive skin, understand its pathophysiology and explore its biomarkers. Here, we analysed RNAs in skin surface lipids (SSL‐RNAs), which can be obtained non‐invasively by wiping the skin surface with an oil‐blotting film, to compare the transcriptome profiles between questionnaire‐based "sensitive" (n = 11) and "non‐sensitive" (n = 10) skin participants. Exactly 417 differentially expressed genes in SSL‐RNAs from individuals with sensitive skin were identified, of which C‐C motif chemokine ligand 17 and interferon‐γ pathways were elevated, while 50 olfactory receptor (OR) genes were downregulated. The expression of the detectable 101 OR genes was lower in individuals with sensitive skin compared to that in those with non‐sensitive skin and was particularly associated with the subjective sensitivity among skin conditions. The receiver operating characteristic (ROC) curve demonstrated that the mean expression levels of OR genes in SSL‐RNAs could discriminate subjective skin sensitivity with an area under the ROC curve of 0.836. SSL‐RNA profiles suggest a mild inflammatory state in sensitive skin, and overall OR gene expression could be a potential indicator for sensitive skin. [ABSTRACT FROM AUTHOR]

Mammalian cadherin-6 (K-cadherin, cad6) was originally identified by means of the polymerase chain reaction, but its biological functions have not yet been determined. We analyzed the expression pattern of the mouse homologue of this cadherin during development and found that it was transiently expressed in restricted rhombomeres and in other subdivisions of the neural plate and tube. In the midbrain and anterior hindbrain of E8.0-8.5 embryos, cad6 was expressed only in neural crest-generating regions. In contrast, in the posterior hindbrain and contiguous spinal cord of these embryos, cad6 occurred throughout the neural plate, forming a sharp anterior limit at the future rhombomere 4 and 5 boundary. Subsequently, this neural plate expression became confined to rhombomere 6, although most of the neural crest-generating areas remained positive throughout the body. Neural crest cells expressing cad6 migrated out of the neural tube, and subsequently accumulated mainly along peripheral nerves. We then studied the effect of Hoxa-1 mutation on the expression of cad6, as their expressions spatiotemporally overlapped with each other in the early posterior hindbrain. In E8.0-8.5 Hoxa-1 mutants, cad6 expression was suppressed in the region of rhombomeres 4 to 6, although that in the other regions was not essentially affected. At later stages, however, cad6-positive crest cells appeared and migrated out of rhombomeres 4 to 6, indicating that the suppression of cad6 expression was transient and restricted to early stages. Importantly, this effect of the Hoxa-1 mutation concurred with the timing of the expression of this gene. We also studied Hoxa-3 mutants, but found no effect of this mutation on the cad6 expression pattern. These findings suggest that cad6 may contribute to the formation of the segmental structure of the early brain through its ability to confer specific adhesiveness on cells and that Hoxa-1 may be required for early cad6 expression in the posterior hindbrain.

A study was conducted to examine the expression and function of cahedrin, a molecule which plays an important role in cell adhesion, by cloning mouse cad-11 cDNA. In situ hybridization of early mouse embryos revealed cad-11 in the mesodermal layers in the head and tail regions and the mid-to-late primitive streak stages. However, somitization restricted the expression of cad-11 to sclerotome cells and limited its appearance at the peripheral mesenchyme. These results suggest that cad-11 is involved in selective association of mesenchymal cells.

Abstract Background While several mouse strains have recently been developed for tracing neural crest or oligodendrocyte lineages, each strain has inherent limitations. The connection between human SOX10 mutations and neural crest cell pathogenesis led us to focus on the Sox10 gene, which is critical for neural crest development. We generated Sox10-Venus BAC transgenic mice to monitor Sox10 expression in both normal development and in pathological processes. Results Tissue fluorescence distinguished neural crest progeny cells and oligodendrocytes in the Sox10-Venus mouse embryo. Immunohistochemical analysis confirmed that Venus expression was restricted to cells expressing endogenous Sox10. Time-lapse imaging of various tissues in Sox10-Venus mice demonstrated that Venus expression could be visualized at the single-cell level in vivo due to the intense, focused Venus fluorescence. In the adult Sox10-Venus mouse, several types of mature and immature oligodendrocytes along with Schwann cells were clearly labeled with Venus, both before and after spinal cord injury. Conclusions In the newly-developed Sox10-Venus transgenic mouse, Venus fluorescence faithfully mirrors endogenous Sox10 expression and allows for in vivo imaging of live cells at the single-cell level. This Sox10-Venus mouse will thus be a useful tool for studying neural crest cells or oligodendrocytes, both in development and in pathological processes.