MaxEnt Modeling to Estimate the Impact of Climate Factors on Distribution of Pinus densiflora

Pinus densiflora is an important evergreen coniferous species with both economic and ecological value. It is an endemic species in East Asia. Global climate warming greatly interferes with species survival. This study explored the impact of climate change on the distribution of this species and the relationship between its geographical distribution and climate demand, so as to provide a theoretical basis for the protection of P. densiflora under the background of global warming. This research used 565 valid data points and 19 typical climatic environmental factors distributed in China, Japan, and South Korea. The potential distribution area of P. densiflora in East Asia under the last glacial maximum (LGM), mid-Holocene, the current situation and two scenarios (RCP 2.6 and RCP 8.5) in the future (2050s and 2070s) was simulated by the MaxEnt model. The species distribution model toolbox in ArcGIS software was used to analyze the potential distribution range and change of P. densiflora. The contribution rates, jackknife test and environmental variable response curves were used to assess the importance of key climate factors. The area under the receiver-operating characteristic curve (AUC) was used to evaluate model accuracy. The MaxEnt model had an excellent simulation effect (AUC = 0.982). The forecast showed that the Korean Peninsula and Japan were highly suitable areas for P. densiflora, and the area had little change. Moreover, during the LGM, there was no large-scale retreat to the south, and it was likely to survive in situ in mountain shelters. The results suggested that Japan may be the origin of P. densiflora rather than the Shandong Peninsula of China. The distribution area of P. densiflora in the mid-Holocene and future scenarios was reduced compared with the current distribution, and the reduction of future distribution was greater, indicating that climate warming will have certain negative impacts on the distribution of P. densiflora in the future. The precipitation of the warmest quarter (Bio18), temperature seasonality (Bio4), mean annual temperature (Bio1) and mean temperature of the wettest quarter (Bio8) had the greatest impact on the distribution area of P. densiflora

Comprehensive Analysis of the Structure and Function of Peptide:N-Glycanase 1 and Relationship with Congenital Disorder of Deglycosylation

The cytosolic PNGase (peptide:N-glycanase), also known as peptide-N4-(N-acetyl-β-glucosaminyl)-asparagine amidase, is a well-conserved deglycosylation enzyme (EC 3.5.1.52) which catalyzes the non-lysosomal hydrolysis of an N(4)-(acetyl-β-d-glucosaminyl) asparagine residue (Asn, N) into a N-acetyl-β-d-glucosaminyl-amine and a peptide containing an aspartate residue (Asp, D). This enzyme (NGLY1) plays an essential role in the clearance of misfolded or unassembled glycoproteins through a process named ER-associated degradation (ERAD). Accumulating evidence also points out that NGLY1 deficiency can cause an autosomal recessive (AR) human genetic disorder associated with abnormal development and congenital disorder of deglycosylation. In addition, the loss of NGLY1 can affect multiple cellular pathways, including but not limited to NFE2L1 pathway, Creb1/Atf1-AQP pathway, BMP pathway, AMPK pathway, and SLC12A2 ion transporter, which might be the underlying reasons for a constellation of clinical phenotypes of NGLY1 deficiency. The current comprehensive review uncovers the NGLY1’ssdetailed structure and its important roles for participation in ERAD, involvement in CDDG and potential treatment for NGLY1 deficiency

The PK–PD Relationship and Resistance Development of Danofloxacin against Mycoplasma gallisepticum in An In Vivo Infection Model

Mycoplasma gallisepticum is the causative agent of chronic respiratory disease (CRD), a prevalent disease of poultry, which is responsible for significant economic losses in farms. Although several antimicrobial agents are currently recommended for the treatment and prevention of M. gallisepticum infections, investigations of M. gallisepticum have been hampered by their fastidious growth requirements and slow growth rate. As such, little work has been conducted concerning the PK/PD relationship and mechanisms of antibiotic resistance between antimicrobials against M. gallisepticum. In the present study, danofloxacin was orally administrated to the infected chickens once daily for 3 days by an established in vivo M. gallisepticum infection model. Not only the concentrations of danofloxacin in plasma and lung tissues were analyzed, but also the counting of viable cells and changes in antimicrobial susceptibility in air sac and lung were determined. The PK and PD data were fitted by WinNonlin to evaluate the PK/PD interactions of danofloxacin against M. gallisepticum. PCR amplification of quinolone resistance-determining regions (QRDRs) and DNA sequencing were performed to identify point mutations in gyrA, gyrB, parC, and parE of the selected resistant mutant strains. In addition, susceptibility of enrofloxacin, ofloxacin, levofloxacin, gatifloxacin, and norfloxacin against these mutant strains were also determined. The PK profiles indicated that danofloxacin concentration in the lung tissues was higher than plasma. Mycoplasmacidal activity was achieved when infected chickens were exposed to danofloxacin at the dose group above 2.5 mg/kg. The ratios of AUC24/MIC (the area under the concentration-time curve over 24 h divided by the MIC) for 2 log10 (CFU) and 3 log10 (CFU) reduction were 31.97 and 97.98 L h/kg, respectively. Substitutions of Ser-83→Arg or Glu-87→Gly in gyrA; Glu-84→Lys in parC were observed in the resistant mutant strains that were selected from the dose group of 1 and 2.5 mg/kg. MICs of danofloxacin, enrofloxacin, ofloxacin, levofloxacin, gatifloxacin, and norfloxacin against the resistant mutant strains with a single mutation in position-83 were higher than that with a single mutation in position-87. These findings suggested that danofloxacin may be therapeutically effective to treat M. gallisepticum infection in chickens if administered at a dosage of 5.5 mg/kg once daily for 3 days