Myocyte nuclear factor (MNF) is a winged helix transcription factor that is expressed selectively in myogenic stem cells (satellite cells) of adult animals. Using a gene knockout strategy to generate a functional null allele at the Mnf locus, we observed that mice lacking MNF are viable, but severely runted. Skeletal muscles of Mnf؊͞؊ animals are atrophic, and satellite cell function is impaired. Muscle regeneration after injury is delayed and incomplete, and the normal timing of expression of cell cycle regulators and myogenic determination genes is dysregulated. Mnf mutant mice were intercrossed with mdx mice that lack dystrophin and exhibit only a subtle myopathic phenotype. In contrast, mdx mice that also lack MNF die in the first few weeks of life with a severe myopathy. Haploinsufficiency at the Mnf locus (Mnf؉͞؊) also exacerbates the mdx phenotype to more closely resemble Duchenne's muscular dystrophy in humans. We conclude that MNF acts to regulate genes that coordinate the proliferation and differentiation of myogenic stem cells after muscle injury. Animals deficient in MNF may prove useful for evaluation of potential therapeutic interventions to promote muscle regeneration for patients having Duchenne's muscular dystrophy.

The IR4 gene (inverted repeat gene 4) of equine herpesvirus type 1 (EHV-), the homolog of the herpes simplex virus type 1 ICP22 gene, is differentially expressed as a 1.4-kb early transcript and a 1.7-kb late transcript that encode a series of proteins that migrate between 42 to 47 kDa, localize to the nucleus of EHV-1-infected cells, and become packaged within EHV-1 virions (V. R. Holden, G. B. Caughman, Y. Zhao, R. N. Harty, and D. J. O'Callaghan, J. Virol. 68, 4329-4340, 1994). To assess the role of the IR4 protein in EHV-1 gene regulation, an IR4 expression vector was cotransfected with EHV-1 chimeric promoter-CAT reporter constructs and EHV-1 effector plasmids to determine the effects of the IR4 protein on the expression of immediate-early (IE), early, and late promoters. These studies revealed that the IR4 protein: (i) minimally trans-activates EHV-1 promoters, (ii) acts synergistically with the UL3 (ICP27) gene product to trans-activate the IE promoter, (iii) does not interfere with the trans-repression of the IE promoter by the IE protein, (iv) enhances transactivation of early promoters by the IE protein, (v) enhances the transactivation of both early and late promoters by the IE and UL3 proteins, and (vi) interacts synergistically with the IE protein to trans-activate the heterologous HSV-1 ICP4 promoter. These data suggest that the IR4 gene product plays a significant role in EHV-1 gene regulation.

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Photonic signal processing is essential in the optical communication and optical computing. Numerous photonic signal processors have been proposed, but most of them exhibit limited reconfigurability and automaticity. A feature of fully automatic implementation and intelligent response is highly desirable for the multipurpose photonic signal processors. Here, a self-configuring and fully reconfigurable silicon photonic signal processor is proposed and experimentally demonstrated. The proposed photonic signal processor is capable of performing various functions, including multichannel optical switching, optical multiple-input-multiple-output descrambler, and tunable optical filter. All the functions are achieved by complete self-configuration without knowing the inner structure. Our demonstration suggests great potential for chip-scale fully programmable optical signal processing with the self-configuring ability.

We have previously reported that the equine herpesvirus 1 (EHV-1) XbaI G restriction fragment (nucleotides 1436 to 7943 relative to the left terminus of the EHV-1 genome [Kentucky A strain]) is required in combination with the EHV-1 immediate-early (IE) gene to achieve significant activation of two representative EHV-1 late promoter-chloramphenicol acetyltransferase (CAT) recombinants in transient expression assays. In this report, we demonstrate that the XbaI G-encoded UL3 gene (an ICP27 homolog) provides a transacting factor which acts (in combination with the EHV-1 IE gene product) to increase reporter gene expression directed by an EHV-1 late promoter-CAT recombinant plasmid. We show that cloned copies of UL3 can successfully substitute for the XaI G fragment in CAT assays and that stop codon insertion within the UL3 open reading frame inhibits the ability of UL3 to activate reporter gene expression in trans.

The DNA sequence of 3,240 nucleotides of the XbaI G fragment located in the unique long (UL) region of the equine herpesvirus 1 genome revealed two major open reading frames (ORFs) designated UL3 and UL4. The UL3 ORF of 470 amino acids (aa) maps at nucleotides (nt) 4450 to 3038 from the long terminus, and its predicted 51.4-kDa protein product exhibits significant homology to the ICP27 alpha regulatory protein of herpes simplex virus type 1 (HSV-1; 32% identity) and to the ORF4 protein of varicella-zoster virus (13% identity). Interestingly, a zinc finger motif is conserved in the C-terminal domains of both ICP27 of HSV-1 (aa 483 to 508) and UL3 of equine herpesvirus 1 (aa 441 to 466). The UL4 ORF of 343 aa maps at nt 5618 to 4587 and could encode a protein of 38.1 kDa which exhibits significant homology to the UL53 protein (cell fusion protein or glycoprotein K) of HSV-1 (26% identity) and to the ORF5 protein of varicella-zoster virus (33% identity). Analyses of the UL4 amino acid sequence revealed domains characteristic of a membrane-bound glycoprotein and included potential signature sequences for (i) a signal sequence, (ii) two N-linked glycosylation sites, and (iii) four transmembrane domains. Nucleotide sequence analyses also revealed potential TATA boxes located upstream of the UL3 and UL4 ORFs. However, only a single polyadenylation signal (nt 2988 to 2983) was detected downstream of the UL3 ORF. Northern (RNA) blot hybridization and Si nuclease analyses were used to map and characterize the UL3 and UL4 mRNAs. Metabolic inhibitors were used to identify the kinetic class of these two genes. The data revealed that UL3 is an early gene that encodes a 1.6-kb mRNA, while UL4 is a late gene encoding a 3.8-kb mRNA that overlaps the UL3 transcript. Both transcripts were shown by Si nuclease analyses to initiate 24 to 26 nt downstream of their respective TATA boxes and to have a common transcription termination signal as a pair of 3'-coterminal mRNAs.

With the great developments in optical communication technology and large-scale optical integration technology, it is imperative to realize the traditional functions of polarization processing on an integration platform. Most of the existing polarization devices, such as polarization multiplexers/demultiplexers, polarization controllers, polarization analyzers, etc., perform only a single function. Definitely, integrating all these polarization functions on a chip will increase function flexibility and integration density and also cut the cost. In this article, we demonstrate an all-in-one chip-scale polarization processor based on a linear optical network. The polarization functions can be configured by tuning the array of phase shifters on the chip. We demonstrate multiple polarization processing functions, including those of a multiple-input-multiple-output polarization descrambler, polarization controller, and polarization analyzer, which are the basic building blocks of polarization processing. More functions can be realized by using an additional two-dimensional output grating. A numerical gradient descent algorithm is employed to self-configure and self-optimize these functions. Our demonstration suggests great potential for chip-scale, reconfigurable, and fully programmable photonic polarization processors with the artificial intelligence algorithm.

Tunable optical delay lines are one of the key building blocks in optical communication and microwave systems. In this work, tunable optical delay lines based on integrated grating-assisted contradirectional couplers are proposed and experimentally demonstrated. The device performance is comprehensively improved in terms of parameter optimization, apodization analysis, and electrode design. Tunable group delay lines of 50 ps at different wavelengths within the bandwidth of 12 nm are realized with a grating length of 1.8 mm. Under thermal tuning mode, the actual delay tuning range is around 20 ps at 7.2 V voltage. At last, a new scheme adopting an ultra-compact reflector for doubling group delay is proposed and verified, achieving a large group delay line of 400 ps and a large dispersion value up to 5.5 × 10 6 ps∕nm · km within bandwidth of 12 nm. Under thermal tuning mode, the actual delay tuning range is around 100 ps at 8 V voltage.