1 Pulmonary inflammatory diseases such as asthma are characterized by chronic, cell-mediated inflammation of the bronchial mucosa. 2 Recruitment and activation of inflammatory cells is orchestrated by a variety of mediators such as cytokines, chemokines, or adhesion molecules, the expression of which is regulated via the transcription factor nuclear factor kappa B (NF-kB). 3 NF-kB signaling is controlled by the inhibitor of kappa B kinase complex (IKK), a critical catalytic subunit of which is IKK-b. 4 We identified COMPOUND A as a small-molecule, ATP-competitive inhibitor selectively targeting IKK-b kinase activity with a K i value of 2 nM. 5 COMPOUND A inhibited stress-induced NF-kB transactivation, chemokine-, cytokine-, and adhesion molecule expression, and T-and B-cell proliferation. 6 COMPOUND A is orally bioavailable and inhibited the release of LPS-induced TNF-a in rodents. 7 In mice COMPOUND A inhibited cockroach allergen-induced airway inflammation and hyperreactivity and efficiently abrogated leukocyte trafficking induced by carrageenan in mice or by ovalbumin in a rat model of airway inflammation. 8 COMPOUND A was well tolerated by rodents over 3 weeks without affecting weight gain. 9 Furthermore, in mice COMPOUND A suppressed edema formation in response to arachidonic acid, phorbol ester, or edema induced by delayed-type hypersensitivity. 10 These data suggest that IKK-b inhibitors offer an effective therapeutic approach for inhibiting chronic pulmonary inflammation.

Spleen tyrosine kinase (Syk) tyrosine kinase plays essential roles in receptors for Fc portion of immunoglobulins and B cell receptor complex signaling in various inflammatory cells; therefore, inhibitors of Syk kinase may show potential as antiasthmatic/allergic therapeutics. We identified 2-[7-(3,4-dimethoxyphenyl)-imidazo[1,2-c]pyrimidin-5-ylamino]-nicotinamide dihydrochloride (BAY 61-3606), a potent (K i ϭ 7.5 nM) and selective inhibitor of Syk kinase. BAY 61-3606 inhibited not only degranulation (IC 50 values between 5 and 46 nM) but also lipid mediator and cytokine synthesis in mast cells. BAY 61-3606 was highly efficacious in basophils obtained from healthy human subjects (IC 50 ϭ 10 nM) and seems to be at least as potent in basophils obtained from atopic (high serum IgE) subjects (IC 50 ϭ 8.1 nM). B cell receptor activation and receptors for Fc portion of IgG signaling in eosinophils and monocytes were also potently suppressed by BAY 61-3606. Oral administration of BAY 61-3606 to rats significantly suppressed antigen-induced passive cutaneous anaphylactic reaction, bronchoconstriction, and bronchial edema at 3 mg/kg. Furthermore, BAY 61-3606 attenuated antigen-induced airway inflammation in rats. Based on these anti-inflammatory effects of BAY 61-3606 both in vitro and in vivo, it was demonstrated that Syk may play a very critical role in the pathogenesis of allergic reactions.

Recent advancements in genomic analysis technologies have opened up new avenues to promote the efficiency of plant breeding. Novel genomics-based approaches for plant breeding and genetics research, such as genome-wide association studies (GWAS) and genomic selection (GS), are useful, especially in fruit tree breeding. The breeding of fruit trees is hindered by their long generation time, large plant size, long juvenile phase, and the necessity to wait for the physiological maturity of the plant to assess the marketable product (fruit). In this article, we describe the potential of genomics-assisted breeding, which uses these novel genomics-based approaches, to break through these barriers in conventional fruit tree breeding. We first introduce the molecular marker systems and whole-genome sequence data that are available for fruit tree breeding. Next we introduce the statistical methods for biparental linkage and quantitative trait locus (QTL) mapping as well as GWAS and GS. We then review QTL mapping, GWAS, and GS studies conducted on fruit trees. We also review novel technologies for rapid generation advancement. Finally, we note the future prospects of genomics-assisted fruit tree breeding and problems that need to be overcome in the breeding.

Pith parenchyma cells store water in various plant organs. These cells are especially important for producing sugar and ethanol from the sugar juice of grass stems. In many plants, the death of pith parenchyma cells reduces their stem water content. Previous studies proposed that a hypothetical gene might be responsible for the death of stem pith parenchyma cells in, a promising energy grass, although its identity and molecular function are unknown. Here, we identify the gene and note that it is located on chromosome 6 in agreement with previous predictions. Sorghum varieties with a functional allele had stems enriched with dry, dead pith parenchyma cells, whereas those with each of six independent nonfunctional alleles had stems enriched with juicy, living pith parenchyma cells. expression was spatiotemporally coupled with the appearance of dead, air-filled pith parenchyma cells in sorghum stems. Among homologs that are present in flowering plants, also is required for the death of stem pith parenchyma cells. and encode previously uncharacterized NAC transcription factors and are sufficient to ectopically induce programmed death of culture cells via the activation of autolytic enzymes. Taken together, these results indicate that and its ortholog,, are master transcriptional switches that induce programmed death of stem pith parenchyma cells. Thus, targeting the gene will provide an approach to breeding crops for sugar and ethanol production.

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We performed whole-genome Illumina resequencing of 198 accessions to examine the genetic diversity and facilitate the use of soybean genetic resources and identified 10 million single nucleotide polymorphisms and 2.8 million small indels. Furthermore, PacBio resequencing of 10 accessions was performed, and a total of 2,033 structure variants were identified. Genetic diversity and structure analysis congregated the 198 accessions into three subgroups (Primitive, World, and Japan) and showed the possibility of a long and relatively isolated history of cultivated soybean in Japan. Additionally, the skewed regional distribution of variants in the genome, such as higher structural variations on the R gene clusters in the Japan group, suggested the possibility of selective sweeps during domestication or breeding. A genome-wide association study identified both known and novel causal variants on the genes controlling the flowering period. Novel candidate causal variants were also found on genes related to the seed coat colour by aligning together with Illumina and PacBio reads. The genomic sequences and variants obtained in this study have immense potential to provide information for soybean breeding and genetic studies that may uncover novel alleles or genes involved in agronomically important traits.

Sorghum (Sorghum bicolor (L.) Moench) grown locally by Japanese farmers is generically termed Takakibi, although its genetic diversity compared with geographically distant varieties or even within Takakibi lines remains unclear. To explore the genomic diversity and genetic traits controlling biomass and other physiological traits in Takakibi, we focused on a landrace, NOG in this study. Admixture analysis of 460 sorghum accessions revealed that NOG belonged to the subgroup that represented Asian sorghums, and it was only distantly related to American/African accession including BTx623. In an attempt to dissect major traits related to biomass, we generated a recombinant inbred line (RIL) from a cross between BTx623 and NOG, and we constructed a high-density linkage map, based on 3,710 single nucleotide polymorphisms obtained by restriction-site associated DNA sequencing (RAD-seq) of 213 RIL individuals. Consequently, 13 fine QTLs were detected on chromosomes 2, 3, 6, 7, 8, and 9, which included five QTLs for days to heading, three for plant height and total shoot fresh weight; and two for Brix. Furthermore, we identified two dominant loci for plant height as being identical to the previously reported dw1 and dw3. Together, these results corroborate the diversified genome of Japanese Takakibi, and the RIL population and high-density linkage map generated in this study will be useful for dissecting other important traits in sorghum.

PAR-2 participates in the regulation of T cell cytokine production that may be caused by modulation of JNK1 phosphorylation.