Avian influenza virus transmission is suppressed in chickens fed Lactobacillus paracasei expressing the 3D8 single-chain variable fragment protein

The 3D8 single-chain variable fragment (scFv) is a mini-antibody sequence with independent nuclease activity that shows antiviral effects against all types of viruses in chickens and mice. In this study, chickens were treated daily with an oral dose of 109 CFU Lactobacillus paracasei (L. paracasei) expressing either a secreted or anchored 3D8 scFv for three weeks. After L. paracasei administration, the chickens were challenged with avian influenza virus (AIV). From each experimental group, three chickens were directly infected with 100 µL of 107.5 EID50/mL H9N2 AIV and seven chickens were indirectly challenged through contact transmission. oropharyngeal and cloacal swab samples were collected at 3, 5, 7, and 9 days post-inoculation (dpi) from AIV-challenged chickens, AIV Shedding titres were measured by quantitative real-time PCR. Contact transmission in the chickens that were fed 3D8 scFv-secreting L. paracasei showed a significant reduction in viral shedding when compared with other groups. These results suggest that L. paracasei secreting 3D8 provides a basis for the development of ingestible antiviral probiotics with activity against AIV

Genetic associations of in vivo pathology influence Alzheimers disease susceptibility

Introduction Although the heritability of sporadic Alzheimers disease (AD) is estimated to be 60–80%, addressing the genetic contribution to AD risk still remains elusive. More specifically, it remains unclear whether genetic variants are able to affect neurodegenerative brain features that can be addressed by in vivo imaging techniques. Methods Targeted sequencing analysis of the coding and UTR regions of 132 AD susceptibility genes was performed. Neuroimaging data using 11C-Pittsburgh Compound B positron emission tomography (PET), 18F-fluorodeoxyglucose PET, and MRI that are available from the KBASE (Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimers disease) cohort were acquired. A total of 557 participants consisted of 336 cognitively normal (CN) adults, 137 mild cognitive impairment (MCI), and 84 AD dementia (ADD) groups. Results We called 5391 high-quality single nucleotide variants (SNVs) on AD susceptibility genes and selected significant associations between variants and five in vivo AD pathologies: (1) amyloid β (Aβ) deposition, (2) AD-signature region cerebral glucose metabolism (AD-Cm), (3) posterior cingulate cortex (PCC) cerebral glucose metabolism (PCC-Cm), (4) AD-signature region cortical thickness (AD-Ct), and (5) hippocampal volume (Hv). The association analysis for common variants (allele frequency (AF) > 0.05) yielded several novel loci associated with Aβ deposition (PIWIL1-rs10848087), AD-Cm (NME8-rs2722372 and PSEN2-rs75733498), AD-Ct (PSEN1-rs7523) and, Hv (CASS4-rs3746625). Meanwhile, in a gene-based analysis for rare variants (AF < 0.05), cases carrying rare variants in LPL, FERMT2, NFAT5, DSG2, and ITPR1 displayed associations with the neuroimaging features. Exploratory voxel-based brain morphometry between the variant carriers and non-carriers was performed subsequently. Finally, we document a strong association of previously reported APOE variants with the in vivo AD pathologies and demonstrate that the variants exert a causal effect on AD susceptibility via neuroimaging features. Conclusions This study provides novel associations of genetic factors to Aβ accumulation and AD-related neurodegeneration to influence AD susceptibility.The study was supported by grants from the National Research Foundation of Korea (2014M3C7A1046049 and 2018M3C9A5064708 for Choi M and 2014M3C7A1046042 for Lee DY) and grants from the Ministry of Health and Welfare of Korea (HI18C0630 for Mook-Jung IH and Lee DY, and HI19C0149 for Lee DY)

Nusinersen demonstrates effectiveness in treating spinal muscular atrophy: findings from a three-year nationwide study in Korea

IntroductionNusinersen is the first drug approved for spinal muscular atrophy (SMA) treatment. In this study, we aimed to evaluate the long-term safety and efficacy of nusinersen, assess the therapeutic effects based on the treatment initiation timing and baseline motor function, and explore the perception of functional improvement from either parents or patients, utilizing 3-year nationwide follow-up data in South Korea.MethodsWe enrolled patients with SMA who were treated with nusinersen under the National Health Insurance coverage, with complete motor score records available and a minimum treatment duration of 6 months. To evaluate the motor function of patients, the Hammersmith Infant Neurological Examination-2 (HINE-2) was used for type 1 and the Expanded Hammersmith Functional Motor Scale (HFMSE) was used for types 2 and 3 patients. A significant improvement was defined as a HINE-2 score gain ≥5 for patients with type 1 and an HFMSE score ≥ 3 for patients with types 2 and 3 SMA. Effects of treatment timing were assessed. Patients with type 2 were further categorized based on baseline motor scores for outcome analysis. We also analyzed a second dataset from five tertiary hospitals with the information on parents/patients-reported impressions of improvement.ResultsThe study comprised 137 patients, with 21, 103, and 13 patients representing type 1, 2, and 3 SMA, respectively. At the 3-year follow-up, the analysis encompassed 7 patients with type 1, 12 patients with type 2, and none with type 3. Nearly half of all enrolled patients across SMA types (42.8, 59.2 and 46.2%, respectively) reached the 2-year follow-up for analysis. Patients with type 1 SMA exhibited gradual motor function improvement over 1-, 2-, and 3-year follow-ups (16, 9, and 7 patients, respectively). Patients with type 2 SMA demonstrated improvement over 1-, 2-, and 3-year follow-ups (96, 61 and 12 patients, respectively). Early treatment from symptom onset resulted in better outcomes for patients with type 1 and 2 SMA. In the second dataset, 90.7% of 108 patients reported subjective improvement at the 1-year follow-up.ConclusionNusinersen treatment for types 1–3 SMA is safe and effective in long-term follow-up. Early treatment initiation was a significant factor affecting long-term motor outcome

Characteristics of greenhouse gas concentrations derived from ground-based FTS spectra at Anmyeondo, South Korea

Since the late 1990s, the meteorological observatory established in Anmyeondo (36.5382° N, 126.3311° E, and 30 m above mean sea level) has been monitoring several greenhouse gases such as CO_2, CH_4, N_2O, CFCs, and SF_6 as a part of the Global Atmosphere Watch (GAW) Program. A high resolution ground-based (g-b) Fourier transform spectrometer (FTS) was installed at this observation site in 2013 and has been operated within the frame work of the Total Carbon Column Observing Network (TCCON) since August 2014. The solar spectra recorded by the g-b FTS cover the spectral range 3800 to 16 000 cm^(−1) at a resolution of 0.02 cm^(−1). In this work, the GGG2014 version of the TCCON standard retrieval algorithm was used to retrieve total column average CO_2 and CH_4 dry mole fractions (XCO_2, XCH_4) and from the FTS spectra. Spectral bands of CO_2 (at 6220.0 and 6339.5 cm^(−1) center wavenumbers, CH_4 at 6002 cm^(−1) wavenumber, and O_2 near 7880 cm^(−1)) were used to derive the XCO_2 and XCH_4. In this paper, we provide comparisons of XCO_2 and XCH_4 between the aircraft observations and g-b FTS over Anmyeondo station. A comparison of 13 coincident observations of XCO_2 between g-b FTS and OCO-2 (Orbiting Carbon Observatory) satellite measurements are also presented for the measurement period between February 2014 and November 2017. OCO-2 observations are highly correlated with the g-b FTS measurements (r^2 = 0.884) and exhibited a small positive bias (0.189 ppm). Both data set capture seasonal variations of the target species with maximum and minimum values in spring and late summer, respectively. In the future, it is planned to further utilize the FTS measurements for the evaluation of satellite observations such as Greenhouse Gases Observing Satellite (GOSAT, GOSAT-2). This is the first report of the g-b FTS observations of XCO_2 species over the Anmyeondo station