STAT3 couples with 14-3-3σ to regulate BCR signaling,B-cell differentiation,and IgE production

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Altered chromatin landscape in circulating T follicular helper and regulatory cells following grass pollen subcutaneous and sublingual immunotherapy

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Osteotomy around the knee: Assessment of quality,content and readability of online information

BackgroundAs knee osteotomy surgery becomes increasingly accessible, more patients may turn to the Internet for information. This study examined the source, quality, content and readability of online information regarding osteotomy around the knee.MethodsThe first 70 websites returned by the top four search engines were identified using the key words: “knee osteotomy” and “high tibial osteotomy.” The websites were categorised by type and assessed using the DISCERN score, Journal of the American Medical Association (JAMA) benchmark criteria and a novel Knee Osteotomy-Specific Score (KOSS). The presence of the Health On the Net (HON) code accreditation seal was noted. Readability of each website was assessed using eight readability formulae. The mean reading grade level (RGL) was compared to the 6th and 8th grade reading levels. The mean RGL of each category was also compared.ResultsOf the 45 unique websites analysed, the majority were Physician (33%) and Journal websites (31%). The mean DISCERN score was 36.7 (±8.9) which is classified as ‘poor.’ The mean JAMA benchmark criteria score was 2.04 (±1.5) and Physician websites were most likely to be scored zero. The mean KOSS was 15.4 (±5.7). The highest scoring website was a Commercial site but, overall, Journal category sites provided the best quality information. Websites that bore the HONcode seal obtained higher DISCERN, JAMA benchmark criteria and Knee Osteotomy - Specific Scores.The cumulative mean RGL was 13.2 (±2.2) which exceeded the 6th grade level by an average of 7.2 grade levels and the 8th grade level by an average of 5.2 grade levels. No website (0%) was written at or below either the 6th or the 8th grade reading levels. The mean Flesch Reading Ease Score of all websites was 41.13 (±14.7) which is classified as ‘difficult.’ Journal websites had the highest RGL.ConclusionThe information available online regarding osteotomy around the knee varies tremendously in quality and completeness. Physician sites predominate, but these were among the lowest scoring of all websites. Even where high quality information is available, it is set at too high a level to be easily understood.Level of evidenceSurvey of materials – Internet.     

Analysis of evolutionary conservation in CD1d molecules among primates

The hereditary conservation in the genetically encoded CD1D sequences of various primates was analyzed. Genomic CD1D sequences of 17 rhesus macaques with distinct origins, eight Indian and nine Chinese, were examined and differences of only one or two nucleotides were detected and the consensus sequence of rhesus CD1D was determined. CD1D consensus sequences of three African green monkeys (AGMs) and the rhesus monkeys were then compared to study the evolutionary differences among interspecies. The CD1D consensus sequence determined from AGMs apparently differed by seven nucleotides from the rhesus consensus sequence, and nucleotide difference induced only three amino acid changes within Exon3, corresponding to the alpha2 domain of CD1d having a hydrophobic ligand-binding pocket. Such changes in the alpha2 domain may alter the characteristics of the SIV-derived glycolipid/lipid antigens presented by each CD1d molecule to innate natural killer T cells. In addition, the CD1D genomic sequences of three chimpanzees (chimps) were determined. To our surprise, although Exon2 and Exon3 reflecting antigen-binding alpha1 and alpha2 domains in chimps' CD1D were identical to that in humans except one amino acid, three amino acids within Exon4, reflecting alpha3 domain, were distinct from humans, and one of them was identical to those in rhesus and AGM CD1D. On the basis of the findings, the evolutionary relationship of the CD1d molecules among the various primates and their HIV-1/SIV susceptibility will be discussed.     

Mucosal bromodomain-containing protein 4 mediates aeroallergen-induced inflammation and remodeling

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Dual function of Langerhans cells in skin TSLP-promoted TFH differentiation in mouse atopic dermatitis

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Separation of human basophils into two fractions with different density and histamine content

We designed experiments in this study to test the hypothesis suggested by recent purification data that blood basophils comprise two populations of different density, which circulate in numbers characteristic for each human subject. Basophils were separated into two density bands by single step centrifugation on a discontinuous Percoll gradient. Band 1 cells were at the interface between plasma and Percoll of density 1.070 gm/ml. Band 2 cells were at the Percoll 1.070 to 1.080 interface. When the number of band 1 basophils was expressed as a percentage of the total in bands 1 and 2, this relative amount generally remained in a narrow range for blood obtained from the same donor on 3 successive days but differed markedly in different individuals. In a series of leukapheresis experiments, we demonstrated that the percentage of band 1 basophils in postleukapheresis venous blood was strikingly similar to the preleukapheresis value. If basophils that repopulated the leukapheresis-depleted circulation came from the bone marrow, we can conclude that blood levels of basophils in bands 1 and 2 are under physiologic control and that the two types of basophils are released in amounts characteristic for each human subject. Additional evidence for two distinct blood basophil populations was provided by histamine measurements. The histamine content per basophil was consistently higher in cells from band 1 than from band 2, the mean difference between pairs of values for 30 subjects being 0.3 +/- 0.04 pg or about 27% of the band 1 basophil histamine content of 1.1 pg.     

Immunochemical characterization of mouse brain-associated theta (Thy-1) antigen.

The Thy-1 antigens or rat brain and thymus have been isolated and chemically characterized, but those of mice have not been identified. Moreover, it is uncertain whether the antigens are glycolipids or glycoproteins. This study with highly purified preparations of gangliosides GM₁, ¹GD_1a, GD_1b and GT_1b from bovine brain and several ganglioside fractions from mouse brain showed that Thy-1 activity does not reside in gangliosides, but rather in the chloroform-methanol-insoluble residue of brain remaining after extraction of gangliosides. The antigen could be solubilized from this residue with a non-ionic detergent. The antigenic activity of the solubilized preparation was heat-labile but resistant to periodate. The chemical properties of the Thy-1 antigen of mouse brain are discussed.     

A deletion–insertion mutation in the phosphomannomutase 2 gene in an African American patient with congenital disorders of glycosylation‐Ia

Congenital disorders of glycosylation (CDG) are a group of metabolic disorders with multisystemic involvement characterized by abnormalities in the synthesis of N‐linked oligosaccharides. The most common form, CDG‐Ia, resulting from mutations in the gene encoding the enzyme phosphomannomutase (PMM2), manifests with severe abnormalities in psychomotor development, dysmorphic features and visceral involvement. While this disorder is panethnic, we present the first cases of CDG‐Ia identified in an African American family with two affected sisters. The proband had failure to thrive in infancy, hypotonia, ataxia, cerebellar hypoplasia and developmental delay. On examination, she also exhibited strabismus, inverted nipples and an atypical perineal fat distribution, all features characteristic of CDG‐Ia. Direct sequencing demonstrated that the patient had a unique genotype, T237M/c.565‐571 delAGAGAT insGTGGATTTCC. The novel deletion–insertion mutation, which was confirmed by subcloning and sequencing of each allele, introduces a stop codon 11 amino acids downstream from the site of the deletion. The presence of this deletion–insertion mutation at cDNA position 565 suggests that this site in the PMM2 gene may be a hotspot for chromosomal breakage. Published 2002 Wiley‐Liss, Inc.