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The delay jitter in the visible light communication (VLC) network is analyzed in this work. First, the delay jitter under single-user and multi-user scenarios is investigated and a closed-form expression is obtained, whose accuracy is verified by simulation. Second, through analyzing the delay jitter under two typical indoor light emitting diode (LED) layouts, we find that the mean user delay jitter under cellular layout is a little lower than that of square layout. Then, we study the delay jitter for mobile users, and the relationship among user movement speed, arrival rate and delay jitter in different scenarios. The delay jitter performance is evaluated assuming perfect coordinated multiple points (CoMP) transmission strategy in VLC network. Simulation results show that in the context of VLC, static users can experience an average delay jitter of up to $10^{-6}$ s, while mobile users can experience an average delay jitter of up to $10^{-5}$ s. Therefore, VLC network can provide users with good delay jitter performance and customized services to meet the higher service quality requirements of future users.

In the process of synaptic formation, neurons must not only adhere to specific principles when selecting synaptic partners but also possess mechanisms to avoid undesirable connections. Yet, the strategies employed to prevent unwarranted associations have remained largely unknown. In our study, we have identified the pivotal role of combinatorial clustered protocadherin gamma (γ-PCDH) expression in orchestrating synaptic connectivity in the mouse neocortex. Through 5' end single-cell sequencing, we unveiled the intricate combinatorial expression patterns of γ-PCDH variable isoforms within neocortical neurons. Furthermore, our whole-cell patch-clamp recordings demonstrated that as the similarity in this combinatorial pattern among neurons increased, their synaptic connectivity decreased. Our findings elucidate a sophisticated molecular mechanism governing the construction of neural networks in the mouse neocortex.

Abstract In this paper, a wide‐angle beam scanning circularly polarized (CP) phased array element, which consists of a concentric tightly coupled dipole array (TCDA) element with a two‐layer parasitic ring structure and a wideband 90° phase shifter, is proposed. To solve the problem of the scanning blindness zone caused by a concentric layout, the grounded coupling patch for the traditional TCDA element is ‘split’ into a combination of a grounded parasitic ring and coupling patch. This combination structure can not only suppress the in‐band common‐mode resonance but also destroy the scanning blind zone mode formed by the dipole and grounded coupling patch. In addition, a two‐layer parasitic ring structure is introduced to obtain a wider axial ratio (AR) beamwidth relative to a single‐layer structure, so a wide‐angle beam scanning AR is realized. An 8 × 8 left‐handed CP planar array based on the proposed wide‐angle beam scanning CP elements is designed and prototyped. Results show that the array can operate over a 3.2:1 (3.75–12.0 GHz) overlapping bandwidth, meeting an AR

Due to the huge potential of application in the communications, electronic jamming, and radar fields, circularly polarized (CP) array antennas with wide axial ratio (AR) scanning performance at wide frequency bandwidth have received great attention. A wideband scanning CP planar array antenna built by new, tightly coupled dipole array (CP-TCDA) elements, which have achieved promising results in terms of both scanning AR bandwidth and angle range in all scanning planes, is presented in this paper. Based on the shorted transmission line model, a CP-TCDA element arranged along the ±45° direction is constructed, which can shift the middle-frequency scanning blind zone out of band and thus obtain a wideband scanning AR bandwidth. Furthermore, the proposed CP-TCDA element adopts four shorting pins and four square parasitic strips, which improve wide-angle CP performance for xz-plane and diagonal-plane scans, respectively. An $8\times 8$ left-handed CP planar array antenna based on the proposed CP-TCDA elements is designed and prototyped. The results show that the array antenna is able to operate over a 3:1 (4–12 GHz) overlapping bandwidth, and it meets the requirements of AR < 3 dB and active VSWR < 2.9 within a ±45° scanning angle range.

Recently, visible light communication (VLC) in the industrial Internet of Things has been widely concerned. In these systems, multi-access technologies are always used to eliminate interference between adjacent transmitters, significantly decreasing transmission efficiency. Meanwhile, the attocell boundaries caused by multi-access technologies can also limit communication coverage and lead to frequent receiving switches. To overcome these weaknesses caused by the division of attocell, we design a boundaryless none-attocell VLC system in this paper. In the proposed system, each transmitter uses all available communication resources, and a cubic receiver is adopted to receive in both non-overlapping and overlapping areas. Specifically, we propose a scheme for adaptive signal selection, enabling the receiver to select the recoverable transmitting signals. After that, we introduce an adaptive channel estimation and signal recovery method, which adaptively achieves signal combining and overlapping signal recovery. Our simulations verify the proposed scheme and demonstrate that the proposed system with the adaptive receiving scheme has better error performance and broader communication coverage than the traditional attocell system.

Recently, visible light communication (VLC) has become a promising option for secure data transmission in industrial Internet of Things (IIoTs). In IIoT-VLC systems, small attocells are adopted to achieve higher spatial reuse rate, and the transmission of data, control and feedback bursts often requires high efficiency and real-time feature. Conventionally, multi-field (MF) frames are used in VLC systems which consists of sync header, channel training sequence, check field, etc. in addition to data payload. However, for short burst transmission, MF frames could result in efficiency loss and latency increase due to useless padding bits. In this paper, a novel coding scheme named integrated frame code (IFC) in physical layer to realize efficient and real-time transmission simultaneously is presented. IFC scheme reduces latency by simplifying transmission procedure and decreases overhead redundancy by integrated design. Specifically, we propose a joint soft-decision criterion for receiving without separate synchronization and channel estimation and then analyze its error performance. After that, we present IFC construction criterion and two design examples. At last, simulation results confirm that for short burst transmission, IFC achieves better efficiency and robustness than MF especially in moving process.

Abstract To minimise the profile of Satcom‐on‐the‐Move ground terminals, in this study, a two‐dimensional beam‐scanning continuous transverse stub antenna that is based on a compact linear source generator (LSG) is presented. A periodic anti‐symmetric two‐step (ASTS) structure cascaded with a broadband network is used to construct a single‐layer compact LSG. The concept of a parallel‐plate waveguide polarisation twister is used to design the ASTS unit that acts as a TE10‐to‐transverse electromagnetic wave converter, to which chamfers and T‐type grooves are added to improve the output plane wave performance over the entire frequency band. A prototype array operating in the band 10.95–12.75 GHz is designed, fabricated, and measured, and the experimental results agree well with the simulated ones. A beam‐scanning range of ±61° in elevation is achieved at the central frequency. Although only 29 of 36 slots (ϕ = 0°) contribute to the radiation, the antenna aperture efficiency is still over 60% due to the superior performance of the single‐layer minimised LSG.

We consider an industrial internet of things environment, where involves multiple production factors, such as automatic guided vehicles (AGVs), people, container, etc. A deep learning model is presented for multi-target recognition, where the training data is shadow image formed by the nonuniform illumination of LED lighting source. Three shadow models of typical shapes are constructed to describe the shadows at different positions. The performance of the optimal VGG-16-based Faster-RCNN model is analyzed in view of the recognition accuracy and speed, and it is proved that recognizing three, four, and five types of objects, the mean average precision is 93%, 94.8%, and 92.6%, respectively. To enhance the generalization performance, the optimal Faster-RCNN is combined with the motion state of objects and the corresponding threshold. Simulation results show that the proposed deep learning model obtains significant performance gains to reduce missed and false detection.

In visible light communication (VLC) system, the intensity of light emitting diode (LED) is modulated to transmit data. As a transmitter, the design of LED should consider the performance of lighting and communication simulataneously. However, the output flux of LED is jointly determined by the electrical and thermal characteristics, and is concave-related to the forward bias current. In order to maximize the use of LEDs, in this paper, the mutual restriction of optical, electrical and thermal mechanisms for the LED systems are considered, and a dynamic photoelectrothermal model is established. Then, the optimal bias current is presented according to the electrical-thermal relationship of LED. Modulating LED at this bias current can maximize the communication performance without sacrificing the light flux. Finally, a BER experiment to verify the optimal communication performance is conducted at this bias current.

We propose a transceiver design method based on an autoencoder (AE) network for multi-color visible light communication (VLC) systems. Taking into account the chromaticity constraint described by MacAdam ellipses and the peak-value constraint of transmitted signals, the proposed AE network utilizes a peak-value constraint layer and an integrated loss function which different from previous AE designs. The new structure of AE network can be suitable for VLC systems with different numbers of colors. Additionally, noisy channel state information (CSI) is employed during the training of the AE in order to achieve a better performance for the system with imperfect CSI. After training, a transceiver design with the target of minimizing block error rate (BLER) can be obtained, which simultaneously meets the requirements of lighting. The results of numerical simulation experiments demonstrate that our proposed transceiver design outperforms conventional color shift keying (CSK) constellation design in imperfect CSI channel.

In this paper, we propose a chromaticity-adaptive generalized spatial modulation (CA-GSM) method for multiple-input multiple-output (MIMO) visible light communication (VLC) systems with quadrichromatic LEDs (QLEDs). After the MIMO-VLC system model is constructed, the CA-GSM method based on chromaticity-adaptive constellation optimization is brought forward accounting for the correlated MIMO channel with multi-color crosstalk and quadrangle chromaticity region. This work mainly investigates the optimal active QLED selection pattern in CA-GSM aiming at maximizing the minimum Euclidean distance of received multi-color constellation. Considering power, amplitude and chromaticity constraints, the optimization problem of chromaticity-adaptive constellation is transformed and solved by the linear approximation of Taylor series. Therefore, the design algorithm of CA-GSM is derived with the optimal QLED selection pattern. Simulation results verify that our proposed CA-GSM can achieve performance improvement compared to the multi-stream spatial modulation and the conventional design method without considering channel.

With the development of lighting industry and visible light communication (VLC) technology, multicolor light-emitting diode (LED) has been advised to replace phosphor-converted LED because of its higher modulation bandwidth and better lighting quality. In this paper, we developed an illumination-adapted transceiver design for a quadrichromatic LED based multicolor multiple-input multiple-output VLC system. The multicolor crosstalk caused by spectral overlapping is considered to make the channel model more realistic. The optimization problem of transceiver design is formulated to minimize total mean-square error between transmitted and received signals with the constraints of chromaticity, luminance, and signal range. Since the optimization problem is nonconvex, we develop an iterative algorithm that updates optimization variables to get the optimal transceiver and color mix ratio in the specified color temperature (CT). Simulation results indicate that the proposed method outperforms the existing design methods with the consideration of the crosstalk and has a better system performance with larger CT value.

In visible light communications (VLC), multi-color light emitting diodes (LEDs) have higher modulation bandwidth and better chromatic property compared with traditional phosphor-converted LEDs. For multi-color multi-input single-output (MISO) VLC systems, multiple colors of one LED are not independent with each other since they are limited jointly with chromaticity constraint. In this paper, we develop a novel linear optimal signal constellation (LOSC) for three-color LEDs and four-color LEDs to maximize the minimum Euclidean distance of received signal constellation under lighting constraints. The main signal design problem is formulated as a max-min optimization problem with continuous variables and discrete variables. To solve this problem, we disassemble it into two parts. In the inner part, we develop a linear optimal signal structure under maximum likelihood detection criterion for the fixed average optical power of each color. In the outer part, we transform the non-convex optimization problem into several convex optimization problems with polar coordinate transformations and slack variables. Combining these two parts, our proposed LOSC design scheme shows a lower computation complexity than the exhaustive search scheme. For different given correlated color temperature (CCT) values, the LOSC would always provide an efficient signal design method adaptively. Simulation results demonstrate that our proposed LOSC achieves better bit error rate performances than the conventional schemes.

Since indoor visible light communication (VLC) modulates the information into the light beams emitted from light-emitting diodes, the channel gain is often modeled as the Lambertian model. For different spatial locations of transmitters and receivers, the channel gain for VLC directly changes with several related geometrical parameters. The distinct geometrical feature makes the ergodic capacity of indoor VLC different from that of radio-frequency communication. However, the issue has not been studied currently. In this paper, we propose the lower bounds on the point-to-point capacity, which have simple expressions with respect to the geometrical parameters. Then, by analyzing indoor human mobility, two typical distributions of the geometrical parameters are considered. Correspondingly, we derive the lower bounds on the ergodic capacity, which are related to the variables of the geometrical feature and the distribution model. Furthermore, simulation results show that our lower bounds on the ergodic capacity are effective to reveal the geometrical feature of indoor VLC systems. Moreover, our proposed lower bounds are tight to the numerical upper bounds at high optical signal-to-noise rates, which are the main application zones of indoor VLC systems.

Multi-input multi-output (MIMO) holds great potential in the high-speed transmission of visible light communication (VLC). However, as for the current MIMO-VLC techniques, the error performance is improved by wasting spatial resources, which just drops the core advantage within an MIMO structure. Moreover, they cannot change over the channel, which greatly limits their application range. In this paper, a general design criterion of the channel-adaptive space-collaborative constellation (CASCC) is established for MIMO-VLC systems. Specifically, we not only consider the channel into our criterion, but also build relations among the light-emitting diodes to exploit the spatial resources instead of wasting. Under the criterion, a regular CASCC is particularly designed for $2\times 2$ MIMO-VLC in terms of the basic four-point constellation and the high-order constellation. Correspondingly, a fast maximum likelihood (ML) detection algorithm for CASCC is proposed. Simulation results show that our proposed CASCC obtains better error performance and wider application range compared with the conventional MIMO-VLC schemes. Moreover, the fast ML algorithm reduces the computational complexity without any performance loss.

In this paper, we consider an outdoor visible light communications relaying system in which the relay node needs to transmit both its own information and the information from a source node simultaneously. A superimposed relaying (SR) strategy and the corresponding constellation design are presented. We derive the closed-form dominant term of average bit error rate (BER) for the system, and obtain an optimal power allocation to minimize the average BER. Simulation results demonstrate that SR can improve the error performance of the system significantly.

Rapid tooling technology (RTT) provides an alternative approach to quickly provide wax injection molds for the required products since it can reduce the time to market compared with conventional machining approaches. Removing conformal cooling channels (CCCs) is the key technology for manufacturing injection mold fabricated by rapid tooling technology. In this study, three different kinds of materials were used to fabricate CCCs embedded in the injection mold. This work explores a technology for rapid development of injection mold with high cooling performance. It was found that wax is the most suitable material for making CCCs. An innovative method for fabricating a large intermediary mold with both high load and supporting capacities for manufacturing a large rapid tooling using polyurethane foam was demonstrated. A trend equation for predicting the usage amount of polyurethane foam was proposed. The production cost savings of about 50% can be obtained. An optimum conformal cooling channel design obtained by simulation is proposed. Three injection molds with different cooling channels for injection molding were fabricated by RTT. Reductions in the cooling time by about 89% was obtained. The variation of the results between the experiment and the simulation was investigated and analyzed.

In this paper, a multiple light-emitting diode (LED) collaborated signal design based on amplitude-phase superposition (MLC-APS) for multi-input single-output visible light communication (VLC) systems is proposed. By using the additive unique factorization technique, all the LED chips can be viewed as transmitting in parallel to increase the rate of VLC systems. In the MLC-APS system, each LED adopts on-off-keying (OOK) modulation, and therefore, the influences of peak-to-average power ratio and clipping are reduced significantly. Simulation results show its significant error performance gains over the direct-current-biased optical orthogonal frequency division multiplexing (OFDM) system.

We consider a typical indoor environment, where multiple light-emitting diode (LED) lamps are equipped, and each LED lamp is the base station of an optical cell. A faster-than-Nyquist signal design is presented for multiuser multicell (FTNMM) visible light communication (VLC) broadcasting systems, where all the transmitters transmit independently with a properly designed time delay to achieve multiple times spectral efficiency. The performance of FTNMM is analyzed in view of the minimum Euclidean distance of symbol sequence, and it is proved that the minimum Euclidean distance remains unchanged as transmitter number and symbol length increase. To reduce the complexity of the maximum-likelihood sequence estimation decoding algorithm, a convolutional code structure with dynamic weights and a fast iterative receiver for FTNMM are developed. Simulation results show that the proposed FTNMM obtains significant performance gains over currently available schemes.

In visible light communication (VLC) systems for automotive applications, different kinds of traffic data with intended priority are usually demanded for transmission to meet an important requirement for both driving safety and the simplicity of a receiver, mainly due to a time urgency issue. For this need, a concept called an additively uniquely decomposable constellation (signal amplitude set) group (AUDCG) is proposed in this paper to transmit multilayer data for VLC through constellation cooperation. Then, an optimal AUDCG is designed by minimizing the average optical power subject to a fixed minimum Euclidean distance. One of the significant advantages of this optimal design is fast demodulation of the sum signal from a noisy received signal, as well as fast decoding of individual signal from the estimated sum signal. Another important advantage is that this design allows each user constellation to be flexibly assigned to meet different priority requirements. Computer simulations indicate that our proposed design has better error performance than the currently available time-orthogonal transmission scheme for this application.

In this paper, the design of linear full-diversity space code (FDSC) is considered for an intensity-modulated direct-detection multiple-input-multiple-output optical wireless communication (IM/DD MIMO-OWC) system, in which the channel suffers from log-normal fading and different links have different variances. Utilizing our recently established error performance criterion for the design of FDSC with a maximum-likelihood detector, we formulate the design problem of optimizing both large-scale diversity gain and small-scale diversity into a max-min optimization problem with continuous-discrete mixed design variables. We propose the use of the Farey sequence in number theory as a powerful tool to solve this kind of optimization problem. By taking advantage of some available properties and by developing some new interesting properties on the Farey sequence, a closed-form solution is attained for IM/DD MIMO-OWC equipped with two transmitters and multiple receivers. This optimal design shows that a repetition code with an optimal power allocation is optimal.

Underwater visible light communication (UVLC) is of great interest to the military, industry, and the scientific community. In this paper, a long-distance UVLC system is designed, where the half power angle of light-emitting diode (LED) is narrowed to enhance the optical intensity at the transmitter, and a single photon avalanche diode (SPAD) is employed at the receiver to improve the detection sensitivity. A two-term exponential channel model of a long distance UVLC system with a SPAD receiver is established, and the channel parameters are obtained by Monte Carlo numerical simulation. Furthermore, the SPAD detection algorithm and the optimal detection threshold of the UVLC system are proposed. Simulation results show that the communication distance could be extended to 500 m in pure seawater.

In this paper, we consider an outdoor visible light communication system, in which on-off keying (OOK) modulation is utilized through an atmospheric turbulence-induced slow-fading channel. A new fast blind detection algorithm is proposed by following the generalized likelihood ratio test (GLRT) principle. In addition, a block coding scheme is presented to solve the unique identification issue and, thus, the error floor problem.

Nitrification inhibitors, such as dicyandiamide (DCD), have been shown to decrease leaching from urea- and ammonium-based fertilizers in agricultural soils. The effect of nitrification inhibitors on nitrifier and denitrifier in short- and long-term intensive vegetable cultivation soils was poorly understood. In this study, the pot trial was conducted to investigate the differential responses of nitrifier (amoA-containing bacteria) and denitrifier (nirK-containing bacteria) to DCD in short-(soil S) and long-term (soil L) intensive vegetable cultivation soils. Quantitative polymerase chain reaction (qPCR) and terminal restriction fragment length polymorphism (T-RFLP) were employed to detect the abundance and composition of amoA- and nirK-containing communities. The results indicated that application of DCD led to a consistently higher NH4+-N concentration during the whole incubation in soil L, while it was quickly decreased in soil S after 21 days. Furthermore, DCD induced more severe decrease of the abundance of amoA-containing bacteria in soil L than in soil S. However, the abundance of the nirK-containing community was not significantly affected by DCD in both soils. Long-term vegetable cultivation resulted in a super-dominant amoA-containing bacteria group and less divergence in soil L compared with soil S, and DCD did not cause obvious shifts of the composition of ammonia-oxidising bacteria (AOB). On the contrary, both amoA- and nirK-containing bacterial compositions were influenced by DCD in soil S. The results suggested that long-term intensive vegetable cultivation with heavy nitrogen fertilization resulted in significant shifts of AOB community, and this community was sensitive to DCD, but denitrifiers were not clearly affected by DCD.

Mediator, an evolutionarily conserved multi-protein complex consisting of about 30 subunits, is a key component of the polymerase II mediated gene transcription. Germline deletion of the Mediator subunit 1 (Med1) of the Mediator in mice results in mid-gestational embryonic lethality with developmental impairment of multiple organs including heart. Here we show that cardiomyocyte-specific deletion of Med1 in mice (csMed1-/-) during late gestational and early postnatal development by intercrossing Med1fl/fl mice to α-MyHC-Cre transgenic mice results in lethality within 10 days after weaning due to dilated cardiomyopathy-related ventricular dilation and heart failure. The csMed1-/- mouse heart manifests mitochondrial damage, increased apoptosis and interstitial fibrosis. Global gene expression analysis revealed that loss of Med1 in heart down-regulates more than 200 genes including Acadm, Cacna1s, Atp2a2, Ryr2, Pde1c, Pln, PGC1α, and PGC1β that are critical for calcium signaling, cardiac muscle contraction, arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy and peroxisome proliferator-activated receptor regulated energy metabolism. Many genes essential for oxidative phosphorylation and proper mitochondrial function such as genes coding for the succinate dehydrogenase subunits of the mitochondrial complex II are also down-regulated in csMed1-/- heart contributing to myocardial injury. Data also showed up-regulation of about 180 genes including Tgfb2, Ace, Atf3, Ctgf, Angpt14, Col9a2, Wisp2, Nppa, Nppb, and Actn1 that are linked to cardiac muscle contraction, cardiac hypertrophy, cardiac fibrosis and myocardial injury. Furthermore, we demonstrate that cardiac specific deletion of Med1 in adult mice using tamoxifen-inducible Cre approach (TmcsMed1-/-), results in rapid development of cardiomyopathy and death within 4 weeks. We found that the key findings of the csMed1-/- studies described above are highly reproducible in TmcsMed1-/- mouse heart. Collectively, these observations suggest that Med1 plays a critical role in the maintenance of heart function impacting on multiple metabolic, compensatory and reparative pathways with a likely therapeutic potential in the management of heart failure.

[This corrects the article DOI: 10.1371/journal.pone.0160755.].

For confidential communications in a multi-user MIMO wiretap channel,though no information regarding the illegitimate receiver was presumed at the transmitter,an artificial interference and a precoding technique based on message block were proposed.Except for confidentiality,the effectivity and efficiency of confidential communications were also taken into consideration.The artificial interference selectively degraded the passive illegitimate receiver’ signal while did not effect every legitimate receiver.The precoding technique combined the existed zero-forcing method that used to eliminate the multi-user interference with singular value decomposition (SVD)-based linear precoder so that enhances the efficiency of confidential communications.ulation result shows that this precoding method degrades the illegitimate receiver’ signal to interference plus noise ratio (SINR) even more and enhances the capacity of multi-user MIMO system compared with the precoding method based on single message symbol.

Multiple-input multiple-output (MIMO) technology as an efficient approach to improve the transmission rate in visible light communication (VLC) has been well studied in recent years. In this paper, we focus on the MIMO VLC system using multi-color LEDs in the typical indoor scenario. Besides the correlation of the MIMO channel, the multi-color crosstalk interference and quadrangle chromaticity region are also considered to increase the practicality of this system. With the constraints of power, amplitude and chromaticity, an iterative algorithm to minimize mean-squared-error (MSE) is proposed to jointly design the precoder and equalizer. Our proposed algorithm provides an effective method to get the optimal precoder by updating optimization variables iteratively. As the equalizer matrix is fixed at each iteration, the main non-convex precoding design problem is transformed into a convex optimization problem and then solved. With the utilization of multi-color LEDs, our proposed precoding method would be promising to promote the practical applications of high-speed indoor optical wireless communication. Simulation results show that our proposed method owns better performance than conventional chromaticity-fixed schemes and zero-forcing precoding designs.

With fairness consideration, optimal linear precoding designs for multi-color, multi-user visible light communication (VLC) systems are presented in this paper. Utilizing both the spatial and multi-color resources, the precoding designs are proposed to mitigate the impact of the multi-user interference (MUI) and the multi-color crosstalk. With the constraints of chromaticity, luminance, and signal range, the precoding designs are formulated to achieve the max-min fairness and the maximum sum-rate. Since the closed-form expression for the capacities is not available, the lower and upper bounds are chosen as the performance criterions. To make the optimization problems be easy to be solved by using standard optimization packages, the non-convex problems are cast into convex ones. Subsequently, algorithms are developed to find optimal solutions. Extensive simulation results indicate that the proposed precoding schemes outperform the conventional pseudo inverse method.

PRIP-Interacting protein with methyl transferase domain (PIMT) serves as a molecular bridge between CREB-binding protein (CBP)/ E1A binding protein p300 (Ep300) -anchored histone acetyl transferase and the Mediator complex sub-unit1 (Med1) and modulates nuclear receptor transcription. Here, we report that ERK2 phosphorylates PIMT at Ser(298) and enhances its ability to activate PEPCK promoter. We observed that PIMT is recruited to PEPCK promoter and adenoviral-mediated over-expression of PIMT in rat primary hepatocytes up-regulated expression of gluconeogenic genes including PEPCK. Reporter experiments with phosphomimetic PIMT mutant (PIMT(S298D)) suggested that conformational change may play an important role in PIMT-dependent PEPCK promoter activity. Overexpression of PIMT and Med1 together augmented hepatic glucose output in an additive manner. Importantly, expression of gluconeogenic genes and hepatic glucose output were suppressed in isolated liver specific PIMT knockout mouse hepatocytes. Furthermore, consistent with reporter experiments, PIMT(S298D) but not PIMT(S298A) augmented hepatic glucose output via up-regulating the expression of gluconeogenic genes. Pharmacological blockade of MAPK/ERK pathway using U0126, abolished PIMT/Med1-dependent gluconeogenic program leading to reduced hepatic glucose output. Further, systemic administration of T4 hormone to rats activated ERK1/2 resulting in enhanced PIMT ser(298) phosphorylation. Phosphorylation of PIMT led to its increased binding to the PEPCK promoter, increased PEPCK expression and induction of gluconeogenesis in liver. Thus, ERK2-mediated phosphorylation of PIMT at Ser(298) is essential in hepatic gluconeogenesis, demonstrating an important role of PIMT in the pathogenesis of hyperglycemia.

The peroxisome proliferator-activated receptor-𝛼 (PPAR𝛼) plays a key role in lipid metabolism and energy combustion. Chronic activation of PPAR𝛼 in rodents leads to the development of hepatocellular carcinomas. The ability of PPAR𝛼 to induce expression of its target genes depends on Mediator, an evolutionarily conserved complex of cofactors and, in particular, the subunit 1 (Med1) of this complex. Here, we report the identification and characterization of PPAR𝛼-interacting cofactor (PRIC)-295 (PRIC295), a novel coactivator protein, and show that it interacts with the Med1 and Med24 subunits of the Mediator complex. PRIC295 contains 10 LXXLL signature motifs that facilitate nuclear receptor binding and interacts with PPAR𝛼 and five other members of the nuclear receptor superfamily in a ligand-dependent manner. PRIC295 enhances the transactivation function of PPAR𝛼, PPAR𝛾, and ER𝛼. These data demonstrate that PRIC295 interacts with nuclear receptors such as PPAR𝛼 and functions as a transcription coactivator under in vitro conditions and may play an important role in mediating the effects in vivo as a member of the PRIC complex with Med1 and Med24.