Identification of an RNA-binding perturbing characteristic for thiopurine drugs and their derivatives to disrupt CELF1-RNA interaction.

RNA-binding proteins (RBPs) are attractive targets in human pathologies. Despite a number of efforts to target RBPs with small molecules, it is still difficult to develop RBP inhibitors, asking for a deeper understanding of how to chemically perturb RNA-binding activity. In this study, we found that the thiopurine drugs (6-mercaptopurine and 6-thioguanine) effectively disrupt CELF1-RNA interaction. The disrupting activity relies on the formation of disulfide bonds between the thiopurine drugs and CELF1. Mutating the cysteine residue proximal to the RNA recognition motifs (RRMs), or adding reducing agents, abolishes the disrupting activity. Furthermore, the 1,2,4-triazole-3-thione, a thiopurine analogue, was identified with 20-fold higher disrupting activity. Based on this analogue, we found that compound 9 disrupts CELF1-RNA interaction in living cells and ameliorates CELF1-mediated myogenesis deficiency. In summary, we identified a thiol-mediated binding mechanism for thiopurine drugs and their derivatives to perturb protein-RNA interaction, which provides novel insight for developing RBP inhibitors. Additionally, this work may benefit the pharmacological and toxicity research of thiopurine drugs.

Helical-sampled fiber Bragg grating inscribed by a femtosecond laser in a ring core fiber.

The inscription of a helical-sampled fiber Bragg grating (HSFBG) in a ring core fiber (RCF) using a low repetition rate femtosecond laser point-by-point technique is demonstrated. The reflection spectrum exhibits several peak groups attributed to the helical-sampled structure, with the wavelength interval between different groups determined by the helical pitch. Meanwhile, the number and spacing of the peaks within each group are dictated by the RCF. An investigation into the effects of helical pitch, helical radius, and grating length of the HSFBG on the reflection spectra is conducted. Furthermore, thermal annealing experiments demonstrate that this HSFBG can survive at the temperatures up to 800°C.

A new mode for the diagnosis of angioimmunoblastic T-cell lymphoma.

In order to explore a new mode for the diagnosis of angioimmunoblastic T-cell lymphoma (AITL), 31 cases of AITL and 28 cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) were used as the study subjects. Identifying T follicular helper (TFH) cells with CD4, CD10, Bcl-6, and PD-1, identifying proliferative B cells with CD20 and EZH2, identifying proliferative follicular dendritic cells (FDCs) with CD21 and CD23, and analyzing the value of TFH/B/FDC proliferation and immunolocalization in the diagnosis of AITL. (1) Outside the inherent lymphoid follicles, simultaneous proliferation of TFH/B/FDC (a new diagnostic mode) were observed in AITL [83.87%; 26/31], with their immunolocalizations in the same site [83.87%; 26/31], while this phenomenon was not observed in 28 cases of PTCL-NOS (P<0.05). (2) The sensitivity and specificity of using this new mode to diagnose AITL were both high (83.87%, 100%), which was superior to CD2 (100%, 0%), CD3 (100%, 0%), CD4 (100%, 32.14%), CD5 (100%, 25%), CD10 (61.9%, 100%), Bcl-6 (42.86%, 100%), PD-1 (83.87%, 96.43%), and its Youden Index (0.84) was the highest. The areas under the curve (AUC) of CD10, Bcl-6, PD-1, and new mode to diagnosis AITL were 0.81, 0.71, 0.90, and 0.92, respectively, while the new mode had the highest AUC. The simultaneous proliferation of TFH/B/FDC cells outside the inherent lymphoid follicles can be used to assist in the diagnosis of AITL, and the simultaneous spatiotemporal proliferation of TFH/B/FDC cells is a specific immunomorphology of AITL.

Multiple indeterminate domain (IDD)-DELLA1 complexes participate in gibberellin feedback regulation in peach.

KEY MESSAGE: Peach encodes 14 INDETERMINATE DOMAIN (IDD) transcription factors. PpIDD4, -12 and -13 mediated PpDELLA1 binding to the PpGA20ox1 promoter. Each of these three PpIDD-DELLA1 complexes activated transcription of PpGA20ox1. PpTPR1 and -4 interrupted the interaction of PpIDDs with PpDELLA1. The plant growth regulator gibberellin (GA) plays an important role in the rapid growth of annual shoots in peach. Our previous study showed that the peach cultivar 'FenHuaShouXingTao' (FHSXT), a gibberellic acid receptor (gid1) mutant, accumulates active GAs in annual shoot tips. This mutant enhances GA feedback regulation in peach. The results of this study suggested that the PpIDD-DELLA1 complex is the underlying mechanism of GA feedback regulation in peach. Fourteen IDD genes were identified in peach, and three PpIDDs (PpIDD4, -12 and -13, all from group IV) interacted with PpDELLA1, an important component in GA signaling pathway. Truncation, segmentation and site mutation of the promoter of PpGA20ox1 (a GA biosynthesis gene) showed that all three PpIDD proteins recognized the core motif TTGTC. PpIDD4 and -13 mainly bind to site 3, while PpIDD12 binds to site 5 of the PpGA20ox1 promoter. All three PpIDD-DELLA1 complexes activated the PpGA20ox1 promoter-LUC fusion. These data suggested that PpIDDs bridge PpDELLA1 and the promoter of PpGA20ox1, which then activated the transcription of PpGA20ox1. In addition, PpTPR1 and -4 disrupted the interaction of PpIDDs with PpDELLA1. Our research will be helpful for understanding and possibly modifying the regulation of annual shoot growth and GA biosynthesis.

Genetic characterization and evolutionary analysis of canine parvovirus in Tangshan, China.

Canine parvovirus (CPV) is a major enteric virus of carnivores worldwide that poses a considerable threat to dogs. In this study, we investigated the genetic variation of CPV in Tangshan, China, and the relationships between CPV disease and the vaccination status, age, and gender of dogs. Seventy-seven fecal samples from dogs in Tangshan that tested positive for CPV were obtained for analysis. Twenty-two full-length VP2 gene sequences were successfully amplified. The 22 strains included 17 CPV-2c variants, four new CPV-2a variants, and one new CPV-2b variant. Phylogenetic analysis showed that all of the CPV-2c strains clustered together and were closely related to CPV-2c strains from Asia but distantly related to CPV-2c strains from Europe. Further amino acid sequence analysis showed that, relative to CPV-2c strains from Europe, most of the CPV-2c stains in this study had A5G, F267Y, Y324I, and Q370R mutations. These findings provide a more comprehensive understanding of the variants of CPV circulating in China.

Isolation and phylogenetic analysis of strains of feline calicivirus in Beijing, China.

Feline calicivirus (FCV) is a contagious cat pathogen that causes oral ulceration and/or upper respiratory disease. In this study, we collected 61 samples from a pet hospital in Beijing and used PCR or RT-PCR to detect FCV and feline herpesvirus 1 (FHV-1). Approximately 44.3% (27/61) of the samples were FCV positive, and 23.0% (14/61) were coinfected with FCV and FHV-1. FCV was isolated from 15 samples. One isolate was from a cat with virulent systemic disease (VSD) signs, and 14 isolates were from cats with stomatitis or upper respiratory diseases. The range of genome sequence identity among these isolates was 76.1-100.0%. Four of the isolates were considered to be of the same strain, with sequence identity ranging from 99.5 to 99.7%, and two isolates, BJ-280 and BJ-288, had completely identical sequences. The genomic sequence identity ranged from 76.0 to 88.5% between the 15 isolates and several reference strains, including the F4 and F9 vaccine strains. These results demonstrate that many FCV strains are co-circulating in Beijing. Due to the diversity of FCV in Beijing, it is necessary to monitor the current prevalence of the virus. This study provides more information for the development of effective measures to control FCV.

Temperature-compensated fiber directional-bend sensor based on a sandwiched MMF-PMPCF structure.

An optical fiber directional-bend sensor based on an inline Mach-Zehnder interferometer is proposed and demonstrated. The device consists of a piece of a multimode fiber (MMF) splicing with a polarization-maintaining photonic crystal fiber (PMPCF) and sandwiched by lead in/out single-mode fibers (SMFs). Owing to the larger diameter of the MMF, some high-order modes in fiber are efficiently coupled and transmitted through the PMPCF, and finally interfere with each other in the output SMFs. The experimental results show that a well-defined interference fringe envelope can be obtained in the transmitted spectrum and, when the fiber is bent, both the intensity and the fringe visibility of the interference pattern are changed with the bending curvature. Meanwhile, the bend sensitivities are varied with different bending directions, and the maximum sensitivity is achieved up to -8.33dB/m-1 within the bend range from 0 to 1.7m-1. The proposed device also demonstrates a very low-intensity cross-talk of environment temperature.

Co-located angularly offset fiber Bragg grating pair for temperature-compensated unambiguous 3D shape sensing.

A 10 mm-long three-dimensional shape sensor in a single-mode fiber is described and demonstrated experimentally. The sensor is based on a pair of fiber Bragg gratings inscribed at the same location along the fiber axis but offset along different radial directions away from the fiber center. Each offset grating generates cladding mode resonances over a ${\sim}{20}\;{\rm{nm}}$-wide spectral bandwidth, and the two gratings are also offset in period so that their transmission spectra are separated by 40 nm, and thus non-overlapping and fully distinguishable. Directional bending sensitivity results from the differential amplitude response of the cladding mode resonances from the two gratings, depending on the relative orientation of the bend with the azimuthal direction of the grating offsets. It is further demonstrated that both axial deformation and temperature have no influence on the shape measurement as they both only cause a global wavelength shift of the spectra without amplitude change. The experimental results demonstrate that the shape orientation of an object can be unambiguously determined for bend directions covering the full 360° range around the fiber axis with sensitivities of the order of ${{1}}\;{\rm{dB/}}{{\rm{m}}^{- 1}}$ and small curvatures between 0 and ${{1}}\;{{\rm{m}}^{- 1}}$.

Epidemiological and phylogenetic analysis of canine kobuviruses in Tangshan, China.

Canine kobuviruses (CaKoV) have been found in healthy and diarrheic dogs as well as asymptomatic wild carnivores in various countries. In order to investigate the prevalence and evolution of CaKoV in Tangshan, China, 82 dog fecal samples from pet hospitals in Tangshan were subjected to RT-PCR targeting a segment of the 3D gene of CaKoV. Using this method, we identified CaKoV in 14 samples (17.07%, 14/82). Of the CaKoV-positive samples, 78.57% (11/14) and 50% (7/14) were positive for canine parvovirus and canine coronavirus, respectively. The nucleotide sequences of the 14 strains 96.6%-100% identical to each other and 77.6%-99.2% identical to representative sequences from the NCBI GenBank database. We also amplified the 14 VP1 gene sequences and found that they were 93.3%-99.6% identical to each other and 73.3%-97.8% identical to representative sequences from the NCBI GenBank database. Phylogenetic analysis revealed that the 14 CaKoV strains from Tangshan are closely related to those identified in China and Thailand and display less similarity to those found in Africa, the United States, and Europe. Our data suggest that CaKoV circulated in young pet dogs in Tangshan and displays a high co-infection rate with CCoV and CPV. However, the relationship between the three viruses and their roles in the host requires further investigation.

Correlation of Cerebral White Matter Lesions with Carotid Intraplaque Neovascularization assessed by Contrast-enhanced Ultrasound.

PURPOSE: Carotid atherosclerotic plaque is closely associated with cerebral white matter lesions (WMLs), while intraplaque neovascularization (IPN) contributes significantly to arterial remodeling and plaque vulnerability. In this study, we aim to evaluate the correlation of carotid IPN with cerebral WMLs. METHODS: The presence of IPN and WMLs were assessed by contrast-enhanced ultrasound (CEUS) and MRI respectively. IPN was evaluated utilizing semi-quantification visual grading scale and WMLs was divided according to Fazekas grading scale. We investigated the baseline data, Fazekas grades, and IPN grades among 269 participants. We explored the influences of each variable on Fazekas grades using ordinal logistic regression and evaluated the relationship between IPN grades and WMLs Fazekas grades. RESULTS: Increased age (OR: 1.06, P<0.001), hypertension (OR: 2.17, P=0.002), cerebral infarction (OR: 1.74, P=0.046), and elevated carotid IPN grading were significantly associated with aggravated Fazekas grades (grade 2 or 3). To be specific, people having grade 3, 2, and 1 carotid IPN were 25.84 (P<0.001), 10.64 (P<0.001), and 5.96 (P=0.010) times as likely to have elevated Fazekas grades compared with those who having grade 0 carotid IPN. CONCLUSION: Increased carotid IPN is independently correlated with aggravated cerebral WMLs.

A single nucleotide mutation in GID1c disrupts its interaction with DELLA1 and causes a GA-insensitive dwarf phenotype in peach.

Plant stature is one important factor that affects the productivity of peach orchards. However, little is known about the molecular mechanism(s) underlying the dwarf phenotype of peach tree. Here, we report a dwarfing mechanism in the peach cv. FenHuaShouXingTao (FHSXT). The dwarf phenotype of 'FHSXT' was caused by shorter cell length compared to the standard cv. QiuMiHong (QMH). 'FHSXT' contained higher endogenous GA levels than did 'QMH' and did not response to exogenous GA treatment (internode elongation). These results indicated that 'FHSXT' is a GA-insensitive dwarf mutant. A dwarf phenotype-related single nucleotide mutation in the gibberellic acid receptor GID1 was identified in 'FHSXT' (GID1cS191F ), which was also cosegregated with dwarf phenotype in 30 tested cultivars. GID1cS191F was unable to interact with the growth-repressor DELLA1 even in the presence of GA. 'FHSXT' accumulated a higher level of DELLA1, the degradation of which is normally induced by its interaction with GID1. The DELLA1 protein level was almost undetectable in 'QMH', but not reduced in 'FHSXT' after GA3 treatment. Our results suggested that a nonsynonymous single nucleotide mutation in GID1c disrupts its interaction with DELLA1 resulting in a GA-insensitive dwarf phenotype in peach.

Symmetry selective cladding modes coupling in ultrafast-written fiber Bragg gratings in two-mode fiber.

The lower order cladding mode resonances of a fiber Bragg grating (FBG) are sensitive to fiber bending but their spectral density makes their response to bending very complex. In this work we present a simple method to reduce and control the number of low order cladding mode resonances via FBGs written in a two-mode fiber (TMF) with an ultrafast laser. Owing to the larger core size of the TMF, a slight break of the cylindrical asymmetry of the grating patterns can be induced when using femtosecond side-irradiation with a small change in the writing condition. This allows us to control the mode families coupled by the grating, and in particular to those modes that have positive or negative bending responses along certain bend directions. Experimental results demonstrate that several lower-order neighboring-cladding mode pairs coupled by the asymmetric TMFBG have antagonistic loss responses (by several dB) for different bending directions, thus allowing full 2D bending measurements with many applications in shape sensing. Finally, this device has similar advantages as tilted FBGs, i.e. temperature de-correlation and the possibility of increasing the signal to noise ratio by averaging simultaneous measurements on several pairs of resonances.

Simultaneous measurement of refractive index and temperature with high sensitivity based on a multipath fiber Mach-Zehnder interferometer.

We present and experimentally demonstrate a highly sensitive sensor for simultaneously measuring the refractive index (RI) and temperature based on a multipath fiber Mach-Zehnder interferometer. The sensor is fabricated by sandwiching a segment of weak-coupling seven-core fiber (SCF) with two short multimode fibers, and then splicing it with lead-in and lead-out single-mode fibers, respectively. Six outer cores of the SCF are half-etched chemically for enhancing the interaction between light and matter. A high-quality transmission spectrum with 23 dB fringe visibility is obtained. Due to the strong interaction between the outer core modes and cladding modes with the surrounding medium, the proposed fiber structure exhibits not only an extremely high RI sensitivity of -1802.26 nm/RI unit from 1.427 to 1.442, but also a superior temperature sensitivity of 82 pm/°C from 10°C to 90°C. Moreover, RI and temperature can be discriminated simultaneously by measuring the central wavelength shifts of two transmission notches. This sensor has outstanding advantages of high sensitivity, easy fabrication, simple structure, and low cost, and may find applications in multiparameter highly sensitive sensing.

Probiotics may not prevent the deterioration of necrotizing enterocolitis from stage I to II/III.

BACKGROUND: Probiotic therapy can reduce the incidence of NEC. Therapeutic use of probiotics after NEC diagnosis reduces the severity of NEC in preterm infants or full-term infants is unclear. To evaluate the effect of probiotics on preventing the deterioration of necrotizing enterocolitis (NEC) from stage I to II/III. METHODS: A retrospective matched cohort study was performed. Included patients were ultimately divided into two groups: the probiotic treatment group (probiotics were used ≥4 days) and the no probiotic treatment group. The differences in deterioration trends between the two groups were compared. Additionally, the risk factors associated with the deterioration of NEC were further analyzed with a case-control study. RESULTS: A total of 231 infants met the inclusion criteria. Eighty-one pairs were matched according to similar gestational age and birth weight. Before matching, we found that the rate of deterioration of NEC from stage I to II/III in the group with probiotic treatment was similar to that in the group without probiotic treatment (23.1% [25/108] vs 26.0% [32/123], P = 0.614). After matching, the rate of deterioration of NEC between the two groups still had no significant difference (21.0% [17/81] vs 27.2% [22/81], P = 0.358). Logistic regression analysis showed that sepsis after NEC was an independent risk factor for NEC deteriorating from stage I to II/III (OR 2.378, 95% CI 1.005-5.628, P = 0.049). CONCLUSION: Probiotics may not prevent the deterioration of NEC from stage I to II/III in infants, but this conclusion should be treated with caution.

Analysis on the characteristic of the optical axis perturbation in a total reflection prismring resonator.

The deduction of the augmented 5×5 matrix describing all the possible angular and decentration misalignment perturbation sources on a spherical prism plane during the refraction is presented in detail for the first time. Combining the augmented matrices and the condition of eigenmode self-consistency, the optical axis perturbation properties (described with the optical axis perturbation sensitivity factor SD1, ST1, SD2, and ST2) in a total reflection prism ring resonator are also analyzed. The singular points of the optical axis perturbation sensitivity factor are found at L/R=0.417 for the cases where the misalignments may originate from distinguished type of prisms P1 and P4 in the resonator, respectively. It is shown that the small errors of the prism can cause large optical axis disturbance in the position of the perturbed singular point and its nearby area, and the disturbance for the case where the misalignments originate from prism P1 is more violent than that of prism P4. With some upgrades to find and avoid the singularity of the optical axis in the total reflection prism ring resonator structure successfully, we expect this work will have great potential for designing and optimizing the structure of super-high-precision ring laser gyroscopes.

Automatic methyl assignment in large proteins by the MAGIC algorithm.

Selective methyl labeling is an extremely powerful approach to study the structure, dynamics and function of biomolecules by NMR. Despite spectacular progress in the field, such studies remain rather limited in number. One of the main obstacles remains the assignment of the methyl resonances, which is labor intensive and error prone. Typically, NOESY crosspeak patterns are manually correlated to the available crystal structure or an in silico template model of the protein. Here, we propose methyl assignment by graphing inference construct, an exhaustive search algorithm with no peak network definition requirement. In order to overcome the combinatorial problem, the exhaustive search is performed locally, i.e. for a small number of methyls connected through-space according to experimental 3D methyl NOESY data. The local network approach drastically reduces the search space. Only the best local assignments are combined to provide the final output. Assignments that match the data with comparable scores are made available to the user for cross-validation by additional experiments such as methyl-amide NOEs. Several NMR datasets for proteins in the 25-50 kDa range were used during development and for performance evaluation against the manually assigned data. We show that the algorithm is robust, reliable and greatly speeds up the methyl assignment task.

Influence of the eigenmode polarization deviation on the output Sagnac frequency difference in nonplanar ring resonators.

We present a theoretical model to quantitatively analyze the influence of the eigenmode polarization deviation (described with ellipticity parameter) on the output Sagnac frequency difference in two nonplanar ring resonators with different mirror arrangements. The theoretical and numerical analysis results prove that the deviation of the eigenmode polarization from the ideally circular polarized state will produce a drop of the output Sagnac frequency difference. Furthermore, for the identical ellipticity parameter and incident angles, the decline values along the rotation axis A(2) is more obvious than that along axis A(1). In other words, these results show that the output Sagnac frequency difference can be improved effectively by restraining the eigenmode polarization deviation quantitatively and that these analysis findings are useful for designing and optimizing the structure of laser gyroscopes with super-high precision.

Strain and high-temperature discrimination using a Type II fiber Bragg grating and a miniature fiber Fabry-Perot interferometer.

A novel method for simultaneous measurement of strain and high temperature using a Type II fiber Bragg grating (FBG) and a miniature fiber Fabry-Perot interferometer (MFFPI) is proposed. The MFFPI is produced by fusion splicing a short section of quartz capillary tube with two single-mode fibers, and then it is exposed by a focused femtosecond laser and a phase mask to inscribe a Type II FBG nearby. The reflection spectrum of this sensor is the superposition of the reflection spectrum of the FBG and the interference fringe of the MFFPI. This sensor shows perfect high-temperature and strain responses. Because of the different responses to the uniform variations of strain and temperature, by measuring the reflection peak of FBG and one of the interference dips of the MFFPI, strain and temperature can be simultaneously determined. The resolutions of this particular sensor in measuring strain and temperature are estimated to be ±8.4 µÏµ and ±3.3°C, respectively, in the range from 0 to 1122 µÏµ and from 23°C to 600°C.

Ultralong time response of magnetic fluid based on fiber-optic evanescent field.

The ultralong time (a few hours) response properties of magnetic fluid using etched optical fiber are visualized and investigated experimentally. The operating structure is made by injecting magnetic fluid into a capillary tube that contains etched single-mode fiber. An interesting extreme asymmetry is observed, in which the transmitted light intensity after the etched optical fiber cannot reach the final steady value when the external magnetic field is turned on (referred to as the falling process), while it can reach the stable state quickly once the magnetic field is turned off (referred to as the rising process). The relationship between the response times/loss rates of the transmitted light and the strength of the applied magnetic field is obtained. The physical mechanisms of two different processes are discussed qualitatively.

Study and Test of a New Bundle-Structure Riser Stress Monitoring Sensor Based on FBG.

To meet the requirements of riser safety monitoring in offshore oil fields, a new Fiber Bragg Grating (FBG)-based bundle-structure riser stress monitoring sensor has been developed. In cooperation with many departments, a 49-day marine test in water depths of 1365 m and 1252 m was completed on the "HYSY-981" ocean oil drilling platform. No welding and pasting were used when the sensor was installed on risers. Therefore, the installation is convenient, reliable and harmless to risers. The continuous, reasonable, time-consistent data obtained indicates that the sensor worked normally under water. In all detailed working conditions, the test results show that the sensor can do well in reflecting stresses and bending moments both in and in magnitude. The measured maximum stress is 132.7 MPa, which is below the allowable stress. In drilling and testing conditions, the average riser stress was 86.6 MPa, which is within the range of the China National Offshore Oil Corporation (CNOOC) mechanical simulation results.