Simultaneous deletion of floxed genes mediated by CaMKIIa-Cre in the brain and in male germ cells: application to conditional and conventional disruption of Go-alfa

The Cre/LoxP system is a well-established approach to spatially and temporally control genetic inactivation. The calcium/calmodulin-dependent protein kinase II alpha subunit (CaMKIIα) promoter limits expression to specific regions of the forebrain and thus has been utilized for the brain-specific inactivation of the genes. Here, we show that CaMKIIα-Cre can be utilized for simultaneous inactivation of genes in the adult brain and in male germ cells. Double transgenic Rosa26+/stop-lacZ::CaMKIIα-Cre+/Cre mice generated by crossing CaMKIIα-Cre+/Cre mice with floxed ROSA26 lacZ reporter (Rosa26+/stop-lacZ) mice exhibited lacZ expression in the brain and testis. When these mice were mated to wild-type females, about 27% of the offspring were whole body blue by X-gal staining without inheriting the Cre transgene. These results indicate that recombination can occur in the germ cells of male Rosa26+/stop-lacZ::CaMKIIα-Cre+/Cre mice. Similarly, when double transgenic Gnao+/f::CaMKIIα-Cre+/Cre mice carrying a floxed Go-alpha gene (Gnaof/f) were backcrossed to wild-type females, approximately 22% of the offspring carried the disrupted allele (GnaoΔ) without inheriting the Cre transgene. The GnaoΔ/Δ mice closely resembled conventional Go-alpha knockout mice (Gnao−/−) with respect to impairment of their behavior. Thus, we conclude that CaMKIIα-Cre mice afford recombination for both tissue- and time-controlled inactivation of floxed target genes in the brain and for their permanent disruption. This work also emphasizes that extra caution should be exercised in utilizing CaMKIIα-Cre mice as breeding pairs.Fil: Choi, Chan-Il. Ajou University. School of Medicine; Corea del SurFil: Yoon, Sang-Phil. Ajou University. School of Medicine; Corea del SurFil: Choi, Jung-Mi. Ajou University. School of Medicine; Corea del SurFil: Kim, Sung-Soo. Ajou University. School of Medicine; Corea del SurFil: Lee, Young-Don. Ajou University. School of Medicine; Corea del SurFil: Birnbaumer, Lutz. National Institute of Environmental Health Sciences; Estados Unidos. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Suh-Kim. Haeyoung. Ajou University. School of Medicine; Corea del Su

A study on the key performance indicator of the dynamic positioning system

AbstractThe dynamic positioning system (DPS) maintains an offshore vessel's position and heading under various environmental conditions by using its own thrust. DPS is regarded as one of the most important systems in offshore vessels. So, efficient operation and maintenance of the DPS are important issues. To monitor the DPS, it is necessary to define an appropriate key performance indicator (KPI) that can express the condition of the DPS from the perspective of operational efficiency and maintenance. In this study, a new KPI for the DPS is proposed considering the efficiency of the machinery and controller, the energy efficiency, and the environmental conditions in which the DPS is operated. The KPI is defined as a function of control deviation, energy consumption, and environmental load. A normalization factor is used to normalize the effect of environmental load on the KPI. The KPI value is calculated from DPS simulation and model test data. The possibility of applying the KPI to monitoring of DPS condition is discussed by comparing the values. The result indicates the feasibility of the new KPI

Neuronal ensemble decoding using a dynamical maximum entropy model

As advances in neurotechnology allow us to access the ensemble activity of multiple neurons simultaneously, many neurophysiologic studies have investigated how to decode neuronal ensemble activity. Neuronal ensemble activity from different brain regions exhibits a variety of characteristics, requiring substantially different decoding approaches. Among various models, a maximum entropy decoder is known to exploit not only individual firing activity but also interactions between neurons, extracting information more accurately for the cases with persistent neuronal activity and/or low-frequency firing activity. However, it does not consider temporal changes in neuronal states and therefore would be susceptible to poor performance for nonstationary neuronal information processing. To address this issue, we develop a novel decoder that extends a maximum entropy decoder to take time-varying neural information into account. This decoder blends a dynamical system model of neural networks into the maximum entropy model to better suit for nonstationary circumstances. From two simulation studies, we demonstrate that the proposed dynamic maximum entropy decoder could cope well with time-varying information, which the conventional maximum entropy decoder could not achieve. The results suggest that the proposed decoder may be able to infer neural information more effectively as it exploits dynamical properties of underlying neural networks.open0

Quantitative in vivo measurement of early axonal transport deficits in a triple transgenic mouse model of Alzheimer’s disease using manganese-enhanced MRI

Impaired axonal transport has been linked to the pathogenic processes of Alzheimer’s disease (AD) in which axonal swelling and degeneration are prevalent. The development of non-invasive neuroimaging methods to quantitatively assess in vivo axonal transport deficits would be enormously valuable to visualize early, yet subtle, changes in the AD brain, to monitor the disease progression and to quantify the effect of drug intervention. A triple transgenic mouse model of AD closely resembles human AD neuropathology. In this study, we investigated age-dependent alterations in the axonal transport rate in a longitudinal assessment of the triple transgenic mouse olfactory system, using fast multi-sliced T1 mapping with manganese-enhanced MRI. The data show that impairment in axonal transport is a very early event in AD pathology in these mice, preceding both deposition of Aβ plaques and formation of Tau fibrils

IL-1α Stimulation Restores Epidermal Permeability and Antimicrobial Barriers Compromised by Topical Tacrolimus

In a previous study, we showed that barrier recovery was delayed after acute barrier disruption in the skin treated with topical calcineurin inhibitors. Tacrolimus decreases lipid synthesis and the expressions of antimicrobial peptide (AMP) and IL-1α in the epidermis. IL-1α is an important cytokine for improving barrier function, lamellar body (LB) production, and lipid synthesis in keratinocytes (KCs). We aimed to evaluate whether IL-1α stimulation could restore the barrier dysfunction observed in tacrolimus-treated skin. Topical imiquimod, an IL-1α inducer, restored the epidermal permeability barrier recovery that had been inhibited by tacrolimus treatment in human (n=15) and murine (n=10) skins, and improved stratum corneum integrity by restoring corneodosmosomes in murine skin (n=6). Imiquimod co-applied on the epidermis resulted in an increase in the production of LB and three major lipid synthesis-related enzymes, and in the expressions of mBD3, CRAMP, and IL-1α (n=5). Furthermore, intracutaneous injection of IL-1α restored permeability barrier recovery (n=6). In IL-1 type 1 receptor knockout mice, topical imiquimod was unable to restore permeability barrier recovery after tacrolimus treatment (n=21). In conclusion, IL-1α stimulation induced positive effects on epidermal permeability and antimicrobial barrier functions in tacrolimus-treated skin. These positive effects were mediated by an increase in epidermal lipid synthesis, LB production, and AMP expression.JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article, please go to http://www.nature.com/jid/journalclu

Forming and Sustaining a Learning Community and Developing Implicit Collective Goals in an Open Future Learning Space

This study investigates the role of space, material, and affect in undergraduate and graduate students’ lived experiences within an open Future Learning Space (FLS) and speaks to the call for research on learning communities in learning spaces, as described in Hod, Bielaczyc, and Ben-Zvi (2018). The methodological approach consists of semi-structured phenomenological interviews with thirteen users of the FLS and thematic analysis to uncover themes. Findings suggest the FLS was able to: (1) bring together individuals by producing individual and shared affective responses; (2) hold community together and inform perceptions; and (3) move the community together and shape practices. This study indicates that open FLSs are complex systems constructed by users and can meet some of the criteria for a learning community (LC), especially if we broaden the definitions to take into account implicit versions of an LC

On Correlated Knowledge Distillation for Monitoring Human Pose with Radios

In this work, we propose and develop a simple experimental testbed to study the feasibility of a novel idea by coupling radio frequency (RF) sensing technology with Correlated Knowledge Distillation (CKD) theory towards designing lightweight, near real-time and precise human pose monitoring systems. The proposed CKD framework transfers and fuses pose knowledge from a robust "Teacher" model to a parameterized "Student" model, which can be a promising technique for obtaining accurate yet lightweight pose estimates. To assure its efficacy, we implemented CKD for distilling logits in our integrated Software Defined Radio (SDR)-based experimental setup and investigated the RF-visual signal correlation. Our CKD-RF sensing technique is characterized by two modes -- a camera-fed Teacher Class Network (e.g., images, videos) with an SDR-fed Student Class Network (e.g., RF signals). Specifically, our CKD model trains a dual multi-branch teacher and student network by distilling and fusing knowledge bases. The resulting CKD models are then subsequently used to identify the multimodal correlation and teach the student branch in reverse. Instead of simply aggregating their learnings, CKD training comprised multiple parallel transformations with the two domains, i.e., visual images and RF signals. Once trained, our CKD model can efficiently preserve privacy and utilize the multimodal correlated logits from the two different neural networks for estimating poses without using visual signals/video frames (by using only the RF signals)

Highly Sensitive Hydrazine Chemical Sensor Based on CNT-PdPt Nanocomposites

Bimetallic PdPt nanoparticles were prepared using the chemical reduction method. The PdPt nanoparticles were successfully deposited on thiolated carbon nanotubes (CNTs) to form a CNT-PdPt nanocomposite as an electron mediator for the fabrication of a hydrazine sensor. The PdPt nanoparticles had an average particle size of 2.3 nm and were well dispersed on the surfaces of the CNTs in the prepared CNT-PdPt nanocomposite, as demonstrated using transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD). Based on X-ray photoelectron spectroscopy (XPS) results, the estimated proportions of Pd and Pt in the CNT-PdPt nanocomposite were approximately 3.0% and 3.2%, respectively. A fabricated chemical sensor based on CNT-PdPt was found to exhibit better amperometric activity with respect to the hydrazine oxidation reaction than CNT-Pd, CNT-Pt, and commercial Pd/C and Pt/C catalysts. This sensor exhibited a linear range of 0.55–1,200 μM and a detection limit of 0.28 μM (S/N = 3) with a fast response time (within 5 s). Furthermore, the sensor could be used repeatedly for the consecutive detection of hydrazine with good reusability and storage stability. These properties demonstrate that the CNT-PdPt nanocomposite is a promising electron mediator for the fabrication of amperometric hydrazine sensors

Voltage-Gated Sodium Channel Modulation by a New Spider Toxin Ssp1a Isolated From an Australian Theraphosid

Given the important role of voltage-gated sodium (NaV) channel-modulating spider toxins in elucidating the function, pharmacology, and mechanism of action of therapeutically relevant NaV channels, we screened the venom from Australian theraphosid species against the human pain target hNaV1.7. Using assay-guided fractionation, we isolated a 33-residue inhibitor cystine knot (ICK) peptide (Ssp1a) belonging to the NaSpTx1 family. Recombinant Ssp1a (rSsp1a) inhibited neuronal hNaV subtypes with a rank order of potency hNaV1.7 > 1.6 > 1.2 > 1.3 > 1.1. rSsp1a inhibited hNaV1.7, hNaV1.2 and hNaV1.3 without significantly altering the voltage-dependence of activation, inactivation, or delay in recovery from inactivation. However, rSsp1a demonstrated voltage-dependent inhibition at hNaV1.7 and rSsp1a-bound hNaV1.7 opened at extreme depolarizations, suggesting rSsp1a likely interacted with voltage-sensing domain II (VSD II) of hNaV1.7 to trap the channel in its resting state. Nuclear magnetic resonance spectroscopy revealed key structural features of Ssp1a, including an amphipathic surface with hydrophobic and charged patches shown by docking studies to comprise the interacting surface. This study provides the basis for future structure-function studies to guide the development of subtype selective inhibitors