Search

Litter size has a great impact on the profit of swine producers. Uterine development is an important determinant of reproduction efficiency and could hence affect litter size. Chinese Erhualian pig is one of the most prolific breeds in the world, even though large phenotypic variation in litter size was observed within Erhualian sows. To dissect the genetic basis of the phenotypic variation, we herein conducted genome-wide association studies for total number born and number born alive (NBA) of Erhualian sows. In total, one significant single nucleotide polymorphism (SNP) (P

Summary The Chinese Erhualian pig has the highest record for litter size in the world. However, the genetic mechanism of its high prolificacy remains poorly understood. In our study, large phenotypic variations in litter size were found among Erhualian sows. Significant differences in total number born (TNB) and corpora lutea numbers were observed between sows with high and low estimated breeding values (EBVs) for TNB. To identify single nucleotide polymorphisms (SNPs) associated with TNB, a selective genomic scan was conducted on 18 sows representing the top 10% and 18 sows representing the bottom 10% of EBVs of 177 sows using Illumina Porcine SNP60 genotype data. Genome-wide fixation coefficient (FST) values were calculated for each SNP between the high- and low-EBV groups. A total of 154 SNPs were significantly differentiated loci between the two groups. Of the top 10 highest FST SNPs, rs81399474, rs81400131 and rs81405013 on SSC8 and rs81434499 and rs81434489 on SSC 12 corresponded to previously reported QTL for litter size. The other five SNPs, rs81367039 on SSC2, rs80891106 on SSC7, rs81477883 on SSC12 and rs80938898 and rs80971725 on SSC14, appeared to be novel QTL for TNB. Significant associations between rs81399474 on SSC8 and TNB were confirmed in 313 Erhualian sows. Forty genes were identified around the top 10 highest FST SNPs, of which UCHL1, adjacent to rs81399474, and RPS6KB1 and CLTC, adjacent to rs81434499, have been reported to affect the ovulation rate in pig. The findings can advance understanding of the genetic variations in litter size of pigs.

Embryonic survival rate, an important factor in the fecundity of sows, is affected by endometrium-secreting histotroph. A higher concentration of calcium ion has been observed in the uterus of highly prolific Erhualian sows (EH) compared with those of less prolific (EL) sows. This suggests that EH sows have better establishment and maintenance of pregnancies, thus increasing embryonic survival rate during the peri-implantation period. To understand the mechanisms of how the endometrium-secreting histotroph affects embryonic survival rate during the Erhualian peri-implantation period, the expression patterns of endometrial mRNA in the EH and EL sows on day 12 of gestation were analyzed using RNA sequencing technology. A total of 164 differentially expressed genes (DEGs) were identified (Padj < 0.05, |log2 (FC)| ≥ 1), including 46 upregulated and 118 downregulated genes in EH compared to EL. Gene Ontology enrichment indicated that a subset of DEGs was involved in calcium ion binding and cell adhesion. Solute carrier family 8 member A3 and solute carrier family 24 member 4, identified as upregulated genes (Padj < 0.05) in EH, were considered key candidate genes expressed in the endometrium affecting embryonic survival rate during the peri-implantation period. The results improve understanding of the genetic mechanism underlying the variation in litter size of Erhualian pigs during the peri-implantation period.

BACKGROUND Induction of allergen-specific IgG antibodies is a critical parameter for successful allergen-specific immunotherapy. IgG antibodies can inhibit IgE-mediated mast cell activation through direct allergen neutralization or through the inhibitory receptor FcγRIIb. The affinity of IgE antibodies to the allergen has been shown to be critical for cellular activation. OBJECTIVE Here we addressed the question of affinity thresholds of allergen-specific IgG antibodies for inhibition of mast cell activation using 2 different mAbs against the major cat allergen Fel d 1 both in vitro and in vivo in mice. METHODS Sequences of the 2 high-affinity mAbs were back-mutated to germline, resulting in low-affinity (10 mol/L) antibodies of the exact same specificity. RESULTS Using these newly generated recombinant antibodies, we demonstrate that low-affinity antibodies are still able to inhibit mast cell activation through FcγRIIb but do not neutralize the allergen. CONCLUSION Antibody affinity dictates the mechanism of mast cell inhibition, and IgG antibodies triggering the inhibitory FcγRIIb pathway can show a broader cross-reactivity pattern than previously thought. This indicates that allergen-specific immunotherapy generates a larger protective umbrella of inhibitory IgG antibodies than previously appreciated.

Conformation and dynamics of a chaperone-client interaction at the atomic level show a basic underlying mechanism., Molecular chaperones are essential in aiding client proteins to fold into their native structure and in maintaining cellular protein homeostasis. However, mechanistic aspects of chaperone function are still not well understood at the atomic level. We use nuclear magnetic resonance spectroscopy to elucidate the mechanism underlying client recognition by the adenosine triphosphate-independent chaperone Spy at the atomic level and derive a structural model for the chaperone-client complex. Spy interacts with its partially folded client Im7 by selective recognition of flexible, locally frustrated regions in a dynamic fashion. The interaction with Spy destabilizes a partially folded client but spatially compacts an unfolded client conformational ensemble. By increasing client backbone dynamics, the chaperone facilitates the search for the native structure. A comparison of the interaction of Im7 with two other chaperones suggests that the underlying principle of recognizing frustrated segments is of a fundamental nature.