Ophthalmic findings associated with Australian tick paralysis (holocyclotoxicity) in hospitalized domestic dogs and cats.

OBJECTIVE: To describe ophthalmic findings in hospitalized canine and feline patients with tick paralysis (TP) and investigate possible predisposing factors. ANIMALS STUDIED: Forty-seven dogs and 28 cats hospitalized with TP assessed with an ophthalmic examination performed by an ABVO resident. METHODS: Dogs and cats were hospitalized with TP from October 2021 to January 2022 and had an ophthalmic examination performed by an ABVO resident. Patient signalment data, information regarding tick number and location, hospitalization duration, medications used, and patient paralysis grades were recorded. Statistical analysis was performed to correlate findings. RESULTS: Corneal ulcers developed in up to 34.8% of dogs and up to 42.9% of cats hospitalized with TP. An absent palpebral reflex ipsilaterally increased the odds of a concurrent corneal ulcer being present by 14.7× in dogs and 20.1× in cats (p < .0001). Palpebral reflexes were absent in 38.3% of dogs and 35.7% of cats hospitalized with TP and were correlated with more severe gait paralysis (p = .01) and respiratory paralysis (p = .005) in dogs, and respiratory paralysis in cats (p = .041). STT-1 findings <10 mm/min were present in 27.7% of dogs and 57.1% of cats examined and were associated with increasing gait paralysis (p = .017) and respiratory paralysis (p = .007) in dogs, and increasing gait paralysis in cats (p = .017). CONCLUSIONS: Simple corneal ulcers, loss of a complete palpebral reflex, and reduced STT-1 scores frequently occurred in dogs and cats hospitalized for TP. The frequency of these findings increased as the degree of patient paralysis increased.

Coexistence of two graphene-induced modulation effects on surface plasmons in hybrid graphene plasmonic nanostructures.

Integrating gate-tunable graphene with plasmonic nanostructures or metamaterials offers a great potential in achieving dynamic control of plasmonic response. While remarkable progress has been made in realizing efficient graphene-induced modulations of plasmon resonances, a full picture of graphene-plasmon interactions and the consequent deep understanding on graphene-enabled tuning mechanism remain largely unexplored. Here, we theoretically identify, for the first time, two distinct modulation effects that can coexist in graphene-based plasmonic nanostructure: graphene can influence the plasmon resonances by either acting as equivalent nanocircuit elements or effectively altering their excitation environment, leading to totally different tuning behaviors. A general dependency of tuning features on the graphene-induced impedance, irrespective of structure geometries, is established when graphene serves as nanocircuit elements. We demonstrate that these two modulation effects can be dynamically controlled by appropriately integrating graphene with plasmonic nanostructures, which provide an active window for efficient modulation of surface plasmons. Our findings may pave the way towards realizing dynamic control of plasmonic response, which holds great potential applications in graphene-based active nanoplasmonic devices.

First-Line Use of Core Needle Biopsy for High-Yield Preliminary Diagnosis of Thyroid Nodules.

BACKGROUND AND PURPOSE: Although core needle biopsy was introduced as a diagnostic alternative to fine-needle aspiration, the utility and safety of core needle biopsy for thyroid nodules in a large population has yet to be studied comprehensively. We evaluate core needle biopsy yields on a large-scale basis to investigate its potential in the preliminary diagnosis of thyroid nodules. MATERIALS AND METHODS: Between March 2005 and December 2013, 2448 initially detected thyroid nodules from 2120 consecutive patients who underwent core needle biopsy were retrospectively evaluated. Of these, 72 thyroid nodules from 63 patients were excluded due to prior fine-needle aspiration attempts. The inconclusive and conclusive result rates, diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and unnecessary surgery rate of core needle biopsy were evaluated. RESULTS: With core needle biopsy as the first-line method, the inconclusive result rate was 11.9% (283/2376) and the conclusive result rate was 88.1% (2093/2376). The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of core needle biopsy for the diagnosis of malignancy were 96.7% (1160/1200), 89.7% (347/387), 100% (813/813), 100% (347/347), and 95.3% (813/853), respectively. There were no major complications and 12 minor complications. CONCLUSIONS: We have demonstrated that first-line use of core needle biopsy may well improve diagnostic accuracy in thyroid nodules, reducing inconclusive or false-negative results and unnecessary operations. Such benefits underscore the promising role of core needle biopsy in managing thyroid nodules and optimizing related surgical decision-making.

Microstructure of atmospheric particles revealed by TXM and a new mode of influenza virus transmission.

For control of influenza, firstly it is important to find the real virus transmission media. Atmospheric aerosol particles are presumably one of the media. In this study, three typical atmospheric inhaled particles in Shanghai were studied by the synchrotron based transmission X-ray microscopes (TXM). Three dimensional microstructure of the particles reveals that there are many pores contained in, particularly the coal combustion fly particles which may be possible virus carrier. The particles can transport over long distance and cause long-range infections due to its light weight. We suggest a mode which is droplet combining with aerosol mode. By this mode the transmission of global and pandemic influenzas and infection between inland avian far from population and poultry or human living in cities along coast may be explained.

Novel signaling axis for ROS generation during K-Ras-induced cellular transformation.

Reactive oxygen species (ROS) are well known to be involved in oncogene-mediated cellular transformation. However, the regulatory mechanisms underlying ROS generation in oncogene-transformed cells are unclear. In the present study, we found that oncogenic K-Ras induces ROS generation through activation of NADPH oxidase 1 (NOX1), which is a critical regulator for the K-Ras-induced cellular transformation. NOX1 was activated by K-Ras-dependent translocation of p47(phox), a subunit of NOX1 to plasma membrane. Of note, PKCδ, when it was activated by PDPK1, directly bound to the SH3-N domain of p47(phox) and catalyzed the phosphorylation on Ser348 and Ser473 residues of p47(phox) C-terminal in a K-Ras-dependent manner, finally leading to its membrane translocation. Notably, oncogenic K-Ras activated all MAPKs (JNK, ERK and p38); however, only p38 was involved in p47(phox)-NOX1-dependent ROS generation and consequent transformation. Importantly, K-Ras-induced activation of p38 led to an activation of PDPK1, which then signals through PKCδ, p47(phox) and NOX1. In agreement with the mechanism, inhibition of p38, PDPK1, PKCδ, p47(phox) or NOX1 effectively blocked K-Ras-induced ROS generation, anchorage-independent colony formation and tumor formation. Taken together, our findings demonstrated that oncogenic K-Ras activates the signaling cascade p38/PDPK1/PKCδ/p47(phox)/NOX1 for ROS generation and consequent malignant cellular transformation.

Claudin-1 induces epithelial-mesenchymal transition through activation of the c-Abl-ERK signaling pathway in human liver cells.

Claudins (CLDNs) are a family of integral membrane proteins central to the formation of tight junctions, structures that are involved in paracellular transport and cellular growth and differentiation, and are critical for the maintenance of cellular polarity. Recent studies have provided evidence that CLDNs are aberrantly expressed in diverse types of human cancers, including hepatocellular carcinomas (HCCs). However, little is known about how CLDN expression is involved in cancer progression. In this study, we show that CLDN1 has a causal role in the epithelial-mesenchymal transition (EMT) in human liver cells, and that the c-Abl-Ras-Raf-1-ERK1/2 signaling axis is critical for the induction of malignant progression by CLDN1. Overexpression of CLDN1 induced expression of the EMT-regulating transcription factors Slug and Zeb1, and thereby led to repression of E-cadherin, ß-catenin expression, enhanced expression of N-cadherin and Vimentin, a loss of cell adhesion, and increased cell motility in normal liver cells and HCC cells. In line with these findings, inhibition of either c-Abl or ERK clearly attenuated CLDN1-induced EMT, as evidenced by a reversal of N-cadherin and E-cadherin expression patterns, and restored normal motility. Collectively, these results indicate that CLDN1 is necessary for the induction of EMT in human liver cells, and that activation of the c-Abl-Ras-Raf-1-ERK1/2 signaling pathway is required for CLDN1-induced acquisition of the malignant phenotype. The present observations suggest that CLDN1 could be exploited as a biomarker for liver cancer metastasis and might provide a pivotal point for therapeutic intervention in HCC.

Diffraction regimes of single holes.

We investigate both experimentally and theoretically the far-field diffraction patterns of single circular apertures as a function of their diameters d and at a given illumination wavelength λ. We observe the transition between the well-known pseudoscalar regime of large holes (d≫λ) and the less-known vectorial regime of subwavelength ones (d≪λ). Four different diffraction regimes are identified for different d/λ regions, each one with its polarization dependence. A thorough comparison with a theoretical model, which takes into account both finite hole size and the dielectric properties of the metal, allows us to explain and understand the physical processes leading to this behavior. Our results reveal the subtle interplay between two competing factors, one related to polarization symmetries associated with surface-plasmon excitations and the other originating in the coupling of the field to the waveguide mode of the aperture.

Colloid coalescence with focused x rays.

We show direct evidence that focused x rays enable us to merge polymer colloidal particles at room temperature. This phenomenon is ascribed to the photochemical scission of colloids with x rays, reducing the molecular weight, glass transition temperature, surface tension, and viscosity of colloids. The observation of the neck bridge growth with time shows that the x-ray-induced colloid coalescence is analogous to viscoelastic coalescence. This finding suggests a feasible protocol of photonic nanofabrication by sintering or welding of polymers, without thermal damage, using x-ray photonics.

X-ray diffractometry and topography of lattice plane curvature in thermally deformed Si wafer.

The correlation between the microscopic lattice plane curvature and the dislocation structure in thermal warpage of 200 mm-diameter Czochralski Si (001) wafers has been investigated using high-resolution X-ray diffractometry and topography. It is found that the (004) lattice plane curvature is locally confined between two neighboring slip bands, with the rotation axis parallel to the slip bands. High-resolution topography reveals that the curvature resulted from a fragmented dislocation structure. The local confinement is attributed to the multiplication of the dislocations that are generated between the two slip bands.

Long terminal repeats of porcine endogenous retroviruses in Sus scrofa.

Using PCR, sequencing, and bioinformatic approaches with the genomic DNAs of Korean pigs (domestic, wild, and hybrid with Yorkshire), twelve solitary PERV long terminal repeat elements were identified and analyzed. Structure analysis of the LTR elements indicated that they have different repeat sequences in the U3 region. The PERV-A6-KWP1 and -KWP2 elements bear seven and eight 39-bp repeats, respectively. The R region of the PERV LTR elements was highly conserved in pig and mouse genomes, suggesting that they seem to have originated from a common exogenous viral element and then evolved independently throughout the course of mammalian evolution.

Molecular evolution of the HERV-E family in primates.

More than 50 copies of HERV-E family elements have been estimated to exist in the human genome. Here we examined the recent evolutionary history of the HERV-E family by a PCR approach using genomic DNA from hominoid primates and a human monochromosomal panel. From the HERV-E family, 25 and 68 env fragments, were identified and analyzed from hominoid primates and human chromosomes 1, 2, 3, 4, 6, 7, 8, 10, 11, 12, 13, 14, 15, 16, 17, 19, X, and Y, respectively. They showed 76.7-99.6% sequence similarity to that of HERV-E (accession no. M10976). Phylogenetic analysis of HERV-E env family distinctively divided into two groups (groups I and II) that each contained three subgroups. Divergence times of the two groups were estimated as 10.7 MYr for group I and 41.3 MYr for group II using an average evolutionary rate of 0.3% per MYr. These data are consistent with that of PCR analysis, which showed a band of the HERV-E family in the genomes of the hominoids, Old World monkeys, and New World monkeys. Therefore, the HERV-E family may have integrated into the primate genome after prosimians and New World monkeys diverged. Then they proliferated extensively in the genome of humans and great apes during primate evolution.

Molecular cloning and phylogeny of HERV-E family that is expressed in Japanese monkey (Macaca fuscata) tissues.

More than 50 copies of HERV-E family have been estimated to exist in the human genome. Here, we examined the expression pattern and their relationships of the HERV-E in Japanese monkey tissues by RT-PCR and sequence analysis. The env gene of HERV-E family was expressed in monkey tissues (testis, prostate, kidney, thymus, intestine and stomach) except for cerebellum, pancreas and ovary, exhibiting that they may have transcriptional potential. Phylogenetic analysis of the HERV-E env family from Japanese monkey tissues and our previous data could be divided into two distinctive groups (I and II). They were integrated into the genomes of anthropoids and have evolved at the rate of 0.3% nucleotide differences per MYr through evolutionary divergence in primate evolution. Divergence times of the two groups were estimated as 11.6 MYr for group I and 41.6 MYr for group II. Those HERV-E sequences were extensively proliferated in the genome of humans and great apes. These data will contribute to further studies on the transcriptional potential of the HERV-E family in the Japanese monkey genome and to biomedical knowledge related to human diseases.

Expression of the human endogenous retrovirus HERV-W family in various human tissues and cancer cells.

We examined the structural genes (gag, pol and env) of the human endogenous retrovirus (HERV-W) family from 12 normal human tissues and 18 human cancer cell lines using RT-PCR. For the gag and pol genes, their expression patterns showed tissue or cell specificity, depending on the samples, whereas the env gene was expressed in all tissues and cancer cells examined. To identify active HERV-W elements in tissues and cancer cells, the RT-PCR products were cloned and sequenced. Ninety-five clones for the env gene, 55 clones for the pol gene and 17 clones for the gag gene of the HERV-W family were isolated from human tissues and sequenced, while 85 clones for the env gene, 61 clones for the pol gene and no clones for the gag gene of the HERV-W family were isolated and sequenced from cancer cells. Among these clones, 50 clones from tissues and 44 from cancer cells showed putative amino acids of the HERV-W env gene, while only two clones from cancer cells showed putative amino acids of the HERV-W pol gene. Phylogenetic analysis indicated that several clones identified previously from human monochromosomes had sister relationships with the clones from the different tissues and cancer cells. These data suggest that HERV-W elements are actively expressed in human tissues and cancer cells. These active HERV-W elements deserve further investigation as potential causative agents of various human diseases including cancers.

Endogenous retrovirus HC2 pol fragments in the squirrel monkey: expression, evolution, and phylogeny.

Human endogenous retrovirus HC2 is an incomplete provirus containing the entire gag and pol genes and a 3' LTR, whereas the 5' LTR and env gene are missing. We investigated expression of the HC2 pol gene in the squirrel monkey ( Saimiri sciureus) by RT-PCR. The pol gene was expressed in cerebellum, liver, lung, and spleen of the squirrel monkey, but not in six other tissues tested. RT-PCR products were cloned and sequenced resulting in seven sequences that were analyzed. These sequences showed 73.7-89.2% sequence similarity to HC2 pol genes present in the human genome. No frameshifts or termination codons caused by deletion/insertion or point mutation were found in clones SM-HC27-1 and SM-HC27-4 isolated from squirrel monkey lung tissues. Phylogenetic analysis showed that HC2 pol elements from the squirrel monkey were randomly clustered with those in human genome and the genomes of other nonhuman primates, indicating that substantial evolution of the HC2 elements occurred prior to primate speciation with additional evolution of the elements, independent of each other, after speciation.

Molecular characterization and phylogenetic relationship of HERV-W family in the Macaca fuscata.

A human endogenous retrovirus, HERV-W, has recently been identified on human chromosome 7 and contains a single complete open reading frame putatively encoding an envelope protein. Its env gene was expressed in various tissues, and mainly in human placenta. We investigated env gene of the HERV-W family in the Macaca fuscata (Japanese monkey). The env gene expression was detected in various tissues (testis, prostate, kidney, cerebellum, thymus, placenta, intestine, stomach, ovary) of the Japanese monkey by RT-PCR. Southern blot analysis indicated that the monkey genome contained at least 15 copies of the HERV-W family. Using the PCR approach with the monkey genome, thirteen env fragments of the HERV-W family were identified and analyzed. These env fragments from monkey showed a high degree of sequence similarity (91-94%) to that of human HERV-W (AF072506). Putative amino acid sequences of the env fragments indicated multiple frameshifts and termination codons by deletion/insertion or point mutation in all clones identified in this study. Phylogenetic analysis of the env fragments derived from the monkey genome with those of the human genome showed a random sister relationship.

Acanthopanax senticosus root inhibits mast cell-dependent anaphylaxis.

BACKGROUND: Mast cells synthesize and secrete chemical mediators which play a central role in anaphylaxis. METHODS: The effect of Acanthopanax senticosus root (ASR) on mast cell-dependent anaphylaxis was investigated. RESULTS: ASR inhibited compound 48/80-induced systemic anaphylactic shock at the dose of 1.0 g/kg by 50%. When ASR was given as pre-treatment at concentrations ranging from 0.01 to 2.0 g/l, the histamine release from rat peritoneal mast cells induced by compound 48/80 was reduced in a dose-dependent manner. ASR (2.0 g/kg) also inhibited passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) IgE to 53.17+/-6.62%. Moreover, ASR inhibited tumor necrosis factor-alpha production in a concentration-dependent manner, and the treatment of 1 g/l blocked the production by 32.5+/-3.50% compared to saline value. CONCLUSIONS: ASR may possess effective anti-anaphylactic activity.

Molecular cloning and phylogenetic analysis of the human endogenous retrovirus HERV-K long terminal repeat elements in various cancer cells.

Long terminal repeats (LTRs) of the human endogenous retroviruses K family (HERV-K) have been found to affect expression of genes located nearby. It has been suggested that the HERV-K LTR elements contributed to the structural change in the genome and genetic variation connected to various diseases. We examined the HERV-K LTR elements in human cancer cells. Using genomic DNA from various cancer cells, we performed PCR amplification and identified forty-nine HERV-K LTR elements. Those LTR elements showed a high degree of sequence similarity with human-specific HERV-K LTR elements. A phylogenetic tree, obtained by the neighbor-joining method, revealed that twelve HERV-K LTR elements were closely related to human-specific HERV-K LTR elements. These elements proliferated recently and were detectable in many human cancer cell lines. These results suggest that HERV-K LTR could be implicated in a pathogenic role, although this phenomenon may not directly lead to human cancers. Further studies on the biological function and expression of HERV-K LTR elements in cancer cells are indicated.

Isolation and phylogenetic analysis of HERV-K long terminal repeat cDNA in cancer cells.

Long terminal repeat (LTR) elements of human endogenous retrovirus (HERV-K) may have contributed to disease-associated structural change or genetic variation in the human genome. The LTR elements have been found to be coexpressed with sequences of closely located genes. We identified seven HERV-K LTR elements from mRNA of human cancer cells (HepG2, MCF7, and SiHa), using the RT-PCR approach. Four of them are closely related to the human-specific HERV-K LTR elements with a high degree of sequence homology in a neighbor-joining phylogenetic tree. The data suggest that recently proliferated HERV-K LTR elements are expressed actively in various cancer cells. These HERV-K LTR elements deserve further investigation as potential leads in the treatment of human cancer.