Is national pride a bane or a boon for cross-border acquisitions?

Although existing cross-border M&A research suggests that national pride is associated with higher bid premiums, the underlying rationale behind these national pride bids is unclear. We study two plausible explanations for this phenomenon: payment for a prearranged expansion strategy (real options) and bidders’ lack of experience in a target country (organization learning). Using a sample of cross-border acquisitions of developed-country targets by developing-country acquirers, we perform an extensive media search to identify 36 acquisitions that involve national pride. We divide these 36 acquisitions into those with zero bids completed in that particular country prior to the national pride bid (non-foothold bidders) and those with at least one bid completed in that country before the national pride acquisition (foothold bidders). We find that the higher premium paid in so-called national pride bids is primarily attributable to the non-foothold acquirers. Since non-foothold characteristics can proxy for either lack of experience or higher value of embedded real options, or both, we perform further tests which confirm that the higher premium of national pride bids can be attributed to both channels, supporting both organizational learning theory and real options explanation. We further demonstrate that national pride acquirers underperform operationally post-acquisition, and such underperformance is also attributable to the non-foothold acquirers. One explanation for this finding is the lack of prior acquisition experience of non-foothold bidders

Generation of a stable packaging cell line producing high-titer PPT-deleted integration-deficient lentiviral vectors

The risk of insertional mutagenesis inherent to all integrating exogenous expression cassettes was the impetus for the development of various integration-defective lentiviral vector (IDLV) systems. These systems were successfully employed in a plethora of preclinical applications, underscoring their clinical potential. However, current production of IDLVs by transient plasmid transfection is not optimal for large-scale production of clinical grade vectors. Here, we describe the development of the first tetracycline-inducible stable IDLV packaging cell line comprising the D64E integrase mutant and the VSV-G envelope protein. A conditional self-inactivating (cSIN) vector and a novel polypurine tract (PPT)-deleted vector were incorporated into the newly developed stable packaging cell line by transduction and stable transfection, respectively. High-titer (~107 infectious units (IU)/ml) cSIN vectors were routinely generated. Furthermore, screening of single-cell clones stably transfected with PPT-deleted vector DNA resulted in the identification of highly efficient producer cell lines generating IDLV titers higher than 108 IU/mL, which upon concentration increased to 1010 IU/ml. IDLVs generated by stable producer lines efficiently transduce CNS tissues of rodents. Overall, the availability of high-titer IDLV lentivirus packaging cell line described here will significantly facilitate IDLV-based basic science research, as well as preclinical and clinical applications

Trends and disparities in disease burden of age-related macular degeneration from 1990 to 2019: Results from the global burden of disease study 2019

ObjectivesThis study aims to estimate the trends and disparities in the worldwide burden for health of AMD, overall and by age, sex, socio-demographic index (SDI), region, and nation using prevalence and years lived with disability (YLDs) from Global Burden of Disease (GBD) study 2019.MethodsThis retrospective study presents the prevalent AMD cases and YLDs from 1990–2019, as well as the age-standardized prevalence rate (ASPR) and age-standardized YLD rate (ASYR) of AMD. To measure changes over time, estimated annual percentage changes (EAPCs) of the age-standardized rates (ASRs) were analyzed globally, then studied further by sex, SDI, region, and nation. We included data from the 2019 Global Burden of Disease (GBD) database to examine AMD prevalence and YLDs from 1990–2019 in 204 countries and territories, as well as demographic information such as age, sex, SDI, region, and nation.ResultsGlobally, the number of prevalent AMD cases increased from 3,581,329.17 (95% uncertainty interval [UI], 3,025,619.4–4,188,835.7) in 1990 to 7,792,530 (95% UI, 6,526,081.5–9,159,394.9) in 2019, and the number of YLDs increased from 296,771.93 (95% uncertainty interval [UI], 205,462.8–418,699.82) in 1990 to 564,055.1 (95% UI, 392,930.7–789,194.64) in 2019. The ASPR of AMD had a decreased trend with an EAPC of −0.15 (95% confidence interval [CI], −0.2 to −0.11) from 1990 to 2019, and the ASYR of AMD showed a decreased trend with an EAPC of −0.71 (95% confidence interval [CI], −0.78 to −0.65) during this period. The prevalence and YLDs of AMD in adults over 50 years of age showed a significant increase. The prevalence and YLDs of AMD were significantly higher in females than males, overall. The ASPRs and ASYRs in low SDI regions was greater than in high SDI regions from 1990 to 2019. In addition, increases in prevalence and YLDs differed by regions and nations, as well as level of socio-economic development.ConclusionThe number of prevalent cases and YLDs due to AMD increased over 30 years and were directly linked to age, sex, socio-economic status, and geographic location. These findings can not only guide public health work but also provide an epidemiological basis for global strategy formulation regarding this global health challenge

PB2 segment promotes high-pathogenicity of H5N1 avian influenza viruses in mice

H5N1 influenza viruses with high lethality are a continuing threat to humans and poultry. Recently, H5N1 high-pathogenicity avian influenza virus (HPAIV) has been shown to transmit through aerosols between ferrets in lab experiments by acquiring some mutation. This is another deeply aggravated threat of H5N1 HPAIV to humans. To further explore the molecular determinant of H5N1 HPAIV virulence in a mammalian model, we compared the virulence of A/Duck/Guangdong/212/2004 (DK212) and A/Quail/Guangdong/90/2004 (QL90). Though they were genetically similar, they had different pathogenicity in mice, as well as their 16 reassortants. The results indicated that a swap of the PB2 gene could dramatically decrease the virulence of rgDK212 in mice (1896-fold) but increase the virulence of rgQL90 in mice (60-fold). Furthermore, the polymerase activity assays showed that swapping PB2 genes between these two viruses significantly changed the activity of polymerase complexes in 293T cells. The mutation Ser715Asn in PB2 sharply attenuated the virulence of rgDK212 in mice (2710-fold). PB2 segment promotes high-pathogenicity of H5N1 avian influenza viruses in mice and 715 Ser in PB2 plays an important role in determing high virulence of DK212 in mice

Enhanced Experimental Corneal Neovascularization along with Aberrant Angiogenic Factor Expression in the Absence of IL-1 Receptor Antagonist

PURPOSE. To address the roles of the endogenously produced IL-1ra in the course of corneal neovascularization (CNV). METHODS. CNV was induced by alkali injury and compared in wild-type (WT), IL-1 receptor antagonist (ra) knockout (KO) mice and anti-IL-1ra antibody-treated WT mice 2 weeks after injury. Angiogenic factor expression and leukocyte accumulation in the early phase after injury were quantified by RT-PCR and immunohistochemical analysis, respectively. RESULTS. The mRNA expression of IL-1ra, IL-1␣, and IL-1␤ was augmented, together with infiltration of F4/80 ϩ macrophages and Gr-1 ϩ neutrophils, in corneas after alkali injury. Intracorneally infiltrating macrophages, but not neutrophils, expressed IL-1ra. Compared with WT mice, either IL-1ra KO mice or anti-IL-1ra antibody-treated WT mice exhibited enhanced CNV 2 weeks after injury, as evidenced by enlarged CD31 ϩ areas. Concomitantly, the infiltration of F4/80 ϩ macrophages was more significantly enhanced in IL-1ra KO mice than in WT mice. Intraocular mRNA expression enhancement of vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) was greater in IL-1ra KO mice than in WT mice after injury. Moreover, IL-1␣ and IL-1␤ enhanced VEGF and iNOS expression by murine peritoneal macrophages. CONCLUSIONS. IL-1ra KO exhibited enhanced alkali-induced CNV through enhanced intracorneal macrophage infiltration and increased expression of VEGF and iNOS. (Invest Ophthalmol Vis Sci. 2009;50:4761-4768

Essential contribution of CCL3 to alkali-induced corneal neovascularization by regulating vascular endothelial growth factor production by macrophages

金沢大学がん研究所がん病態制御Purpose: To evaluate the roles of CCL3 and its specific chemokine receptors, CCR1 and CCR5, in alkali-induced corneal neovascularization (CNV). Methods: Chemical denudation of corneal and limbal epithelium was performed on wild-type (WT) BALB/c mice and CCL3-, CCR1-, and CCR5-deficienct (knockout [KO]) counterparts. Two weeks after injury CNV was quantified by immunostaining with anti-CD31. Angiogenic factor expression and leukocyte accumulation in the early phase after injury were quantified by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical analysis, respectively. Results: Alkali injury augmented the intraocular mRNA expression of CCL3 and its receptors, CCR1 and CCR5, together with a transient infiltration of F4/80 positive macrophages and Gr-1 positive neutrophils. Compared with WT mice, CCL3-KO and CCR5-KO mice but not CCR1-KO mice exhibited reduced CNV two weeks after injury both macroscopically and microscopically as evidenced by CD31 positive areas. Concomitantly, the infiltration of F4/80 positive macrophages but not Gr-1 positive neutrophils was significantly attenuated in CCL3-KO mice compared with WT mice. Intracorneal infiltration of CCR5 expressing cells was significantly impaired in CCL3-KO mice compared with WT mice. Alkali injury induced a massive increase in the intraocular mRNA expression of a potent angiogenic factor, vascular endothelial growth factor (VEGF), in WT mice whereas these increments were severely retarded in CCL3-KO mice. Moreover, CCL3 enhanced VEGF expression by murine peritoneal macrophages at both the mRNA and the protein level. Furthermore, topical CCL3 application restored CNV, which was macroscopically and microscopically reduced in CCL3-KO mice after two weeks to levels similar to those found in WT mice. Conclusions: In alkali-induced CNV, CCL3 induced macrophages to infiltrate and produce VEGF by binding to CCR5 but not to CCR1 and eventually promoted angiogenesis. © 2008 Molecular Vision

Molecular Basis of Efficient Replication and Pathogenicity of H9N2 Avian Influenza Viruses in Mice

H9N2 subtype avian influenza viruses (AIVs) have shown expanded host range and can infect mammals, such as humans and swine. To date the mechanisms of mammalian adaptation and interspecies transmission of H9N2 AIVs remain poorly understood. To explore the molecular basis determining mammalian adaptation of H9N2 AIVs, we compared two avian field H9N2 isolates in a mouse model: one (A/chicken/Guangdong/TS/2004, TS) is nonpathogenic, another one (A/chicken/Guangdong/V/2008, V) is lethal with efficient replication in mouse brains. In order to determine the basis of the differences in pathogenicity and brain tropism between these two viruses, recombinants with a single gene from the TS (or V) virus in the background of the V (or TS) virus were generated using reverse genetics and evaluated in a mouse model. The results showed that the PB2 gene is the major factor determining the virulence in the mouse model although other genes also have variable impacts on virus replication and pathogenicity. Further studies using PB2 chimeric viruses and mutated viruses with a single amino acid substitution at position 627 [glutamic acid (E) to lysine, (K)] in PB2 revealed that PB2 627K is critical for pathogenicity and viral replication of H9N2 viruses in mouse brains. All together, these results indicate that the PB2 gene and especially position 627 determine virus replication and pathogenicity in mice. This study provides insights into the molecular basis of mammalian adaptation and interspecies transmission of H9N2 AIVs

BrLAS, a GRAS Transcription Factor From Brassica rapa, Is Involved in Drought Stress Tolerance in Transgenic Arabidopsis

GRAS proteins belong to a plant-specific transcription factor family and play roles in diverse physiological processes and environmental signals. In this study, we identified and characterized a GRAS transcription factor gene in Brassica rapa, BrLAS, an ortholog of Arabidopsis AtLAS. BrLAS was primarily expressed in the roots and axillary meristems, and localized exclusively in the nucleus of B. rapa protoplast cells. qRT-PCR analysis indicated that BrLAS was upregulated by exogenous abscisic acid (ABA) and abiotic stress treatment [polyethylene glycol (PEG), NaCl, and H2O2]. BrLAS-overexpressing Arabidopsis plants exhibited pleiotropic characteristics, including morphological changes, delayed bolting and flowering time, reduced fertility and delayed senescence. Transgenic plants also displayed significantly enhanced drought resistance with decreased accumulation of ROS and increased antioxidant enzyme activity under drought treatment compared with the wild-type. Increased sensitivity to exogenous ABA was also observed in the transgenic plants. qRT-PCR analysis further showed that expression of several genes involved in stress responses and associated with leaf senescence were also modified. These findings suggest that BrLAS encodes a stress-responsive GRASs transcription factor that positively regulates drought stress tolerance, suggesting a role in breeding programs aimed at improving drought tolerance in plants