O等位基因引起ABO基因型与表现型定型差异

保证输血时血清学方面的安全,首要的是对受血者与献血者ABO血型定型,血清学检查通常分两个步骤.正定型通常使用鼠源单克隆抗体检测红细胞表面是否存在A或B抗原.互补的实验即反定型,利用当红细胞上缺乏A或B抗原时,人群可天然产生相对应的抗体的原理,检测血清中是否存在抗-A或者抗-B抗体.确定了受血者红细胞表面的ABO抗原以及血浆中的抗体,便能确定血型,为其提供相合的血液.     

Severe growth deficiency,microcephaly, intellectual disability,and characteristic facial features are due to a homozygous QARS mutation

Glutaminyl tRNA synthase is highly expressed in the developing fetal human brain. Mutations in the glutaminyl-tRNA synthetase (QARS) gene have been reported in patients with progressive microcephaly, cerebral-cerebellar atrophy, and intractable seizures. We have previously reported a new recessive syndrome of severe linear growth retardation, poor weight gain, microcephaly, characteristic facial features, cutaneous syndactyly of the toes, high myopia, and intellectual disability in two sisters of Ashkenazi-Jewish origin (Eur J Med Genet 2014;57(6):288–92). Homozygosity mapping and whole exome sequencing revealed a homozygous missense (V476I) mutation in the QARS gene, located in the catalytic domain. The patient’s fibroblasts demonstrated markedly reduced QARS amino acylation activity in vitro. Furthermore, the same homozygous mutation was found in an unrelated girl of Ashkenazi origin with the same phenotype. The clinical presentation of our patients differs from the original QARS-associated syndrome in the severe postnatal growth failure, absence of epilepsy, and minor MRI findings, thus further expanding the phenotypic spectrum of the glutaminyl-tRNA synthetase deficiency syndromes.     

Collinear facilitation and suppression at the periphery

Collinear facilitation is a common phenomenon in the fovea, but it has been recently challenged at the human periphery. Since physiological studies show that facilitation is found at the periphery but only from outside the receptive field, our hypothesis was that facilitation at the periphery exists but from larger target-flanker separations than the fovea. Here, we applied a recent paradigm (Polat & Sagi, 2007) to probe facilitation at the periphery. We used a Yes/No detection task by measuring the false-positive reports (false-alarm, pfa) and hit-rate (phit) for a low-contrast Gabor target (between two flankers) that appeared randomly at the fovea or at the periphery (2° or 4°) to the right or left side. We used different target-flanker separations and orientations at the fovea and at the periphery. Importantly, we found that phit is affected by the target-flanker separations and orientations. Short distances show a suppression effect, but the range of suppression increases with increasing eccentricity. A facilitation effect was found for collinear configuration outside of the suppression range. A similar effect was found for the decisional criterion (Cr), which was correlated with suppression (positive) and facilitation (negative). All together, our results indicate that facilitation exists at the periphery when the target-flanker distance is properly scaled. Thus, our results indicate that collinear facilitation is a common phenomenon that exists in both the periphery and fovea. The suppression range indicates that the perceptual receptive field increases with increasing eccentricity. Our results provide a working hypothesis that explains the functional differences found between the fovea and the periphery. This supports the basic phenomena underlying visual perception, such as collinear facilitation, visual crowding, and backward masking.     

In vivo studies support the role of trafficking and cytoskeletal-binding motifs in the interaction of MESA with the membrane skeleton of Plasmodium falciparum-infected red blood cells

In red blood cells (RBCs) infected with the malaria parasite Plasmodium falciparum, a 19-residue region of the mature parasite-infected erythrocyte surface antigen (MESA) associates with RBC cytoskeleton protein 4.1R; an interaction essential for parasite survival. This region in MESA is adjacent to a host targeting motif found in other malaria parasite proteins exported to the membrane skeleton. To demonstrate function of these motifs in vivo, regions of MESA fused to a reporter were expressed in malaria parasites. Immunochemical analyses confirmed the requirement for both motifs in the trafficking and interaction of MESA with the cytoskeleton and demonstrates their function in vivo.     

The exception that reinforces the rule: crosspriming by cytosolic peptides that escape degradation

The nature of crosspriming immunogens for CD8(+) T cell responses is highly controversial. By using a panel of T cell receptor-like antibodies specific for viral peptides bound to mouse D(b) major histocompatibility complex class I molecules, we show that an exceptional peptide (PA(224-233)) expressed as a viral minigene product formed a sizeable cytosolic pool continuously presented for hours after protein synthesis was inhibited. PA(224-233) pool formation required active cytosolic heat-shock protein 90 but not ER g96 and uniquely enabled crosspriming by this peptide. These findings demonstrate that exceptional class I binding oligopeptides that escape proteolytic degradation are potent crosspriming agents. Thus, the feeble immunogenicity of natural proteasome products in crosspriming can be attributed to their evanescence in donor cells and not an absolute inability of cytosolic oligopeptides to be transferred to and presented by professional antigen-presenting cells.     

Inducible heat shock protein 70 prevents multifocal flat dysplastic lesions and invasive tumors in an inflammatory model of colon cancer

Background: Heat shock protein 70 (Hsp70) regulates proteinbiosynthesis and refolding of denatured proteins. Since Hsp70participates in recovery from stress injury, we examined theeffect of Hsp70 genetic deletion in the azoxymethane (AOM)/dextransulfate sodium (DSS) model of inflammation and colon cancer.Methods: Hsp70 mutant mice (Hsp70.1^–/–/70.3^–/–)and wild-type (WT) littermates received AOM and three cyclesof DSS and were killed 24 weeks later. Tumors were graded forhistology and immunostained for p53, adenomatous polyposis coli,β-catenin, cyclooxygenase-2 (Cox-2) and inducible nitricoxide synthase (iNOS) and sequenced for p53 mutations. Results:Elevated adenomas developed in 4/10 WT mice with no dysplasiain adjacent mucosa. In contrast, 7/8 Hsp70 knock out (KO) micedeveloped chronic mucosal inflammation and multifocal areasof flat dysplasia and 4/8 progressed to invasive carcinomasarising in a background of flat dysplastic mucosa. These differencesin the incidence of flat dysplasia and invasive cancers weresignificant (P < 0.05). Nuclear p53 was stronger in Hsp70KO tumors compared with WT tumors, and sequencing confirmedp53 mutations in 2/5 tumors from Hsp70^–/– versus0/5 in WT mice. In Hsp70 WT tumors, β-catenin was predominantlynuclear, compared with membranous β-catenin in Hsp70^–/–tumors, suggesting that Hsp70 regulates β-catenin in colonictumorigenesis. Cox-2 and iNOS levels were increased in tumorsfrom Hsp70^–/– mice compared with Hsp70 WT tumors.Conclusions: Hsp70-deleted mice treated with AOM/DSS developflat invasive colonic tumors that mimic many histological andmolecular features of ulcerative colitis colon cancer. Thismodel will be useful to dissect the role of Hsp70 in inflammatorybowel disease colon cancer. Abbreviations: AOM, azoxymethane; Apc, adenomatous polyposis coli; Cox-2, cyclooxygenase-2; DSS, dextran sulfate sodium; Hsp70, heat shock protein 70; IBD, inflammatory bowel disease; IL, interleukin; iNOS, inducible nitric oxide synthase; PCR, polymerase chain reaction; UC, ulcerative colitis; WT, wild-type