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Background: The null phenotype in P1PK blood group, known as "p," is extremely rare in the whole world. Individuals of p phenotype spontaneously form anti‐PP1PK isoantibody. Here, we report a case of p phenotype with naturally occurring anti‐PP1PK isoantibodies in a Chinese individual. Study Design and Methods: Serology tests, containing alloantibodies screening and identification, were conducted to demonstrate the phenotype in P1PK blood group. The genotype of A4GALT gene was identified by haplotypes separation and sequencing. Results: The serological assay demonstrated the p phenotype of the proband, presenting with 1:64 titer of anti‐PP1PK. The sequencing data revealed a compound heterozygote consisting of A4GALT*P1.01 with c.343A>T and a novel allele based on A4GALT*01N.05 with an addition polymorphism c.100G>A. The sequence of the novel allele has been submitted to GenBank and the accession number OM912503 was assigned. Conclusion: Our study demonstrates a case of naturally occurring anti‐PP1Pk in a Chinese individual with p phenotype, which is based on compound heterozygosity including one novel allele. As the proband is a young lady, monitoring the titer of anti‐PP1PK and early initiation of medical intervention are essential after her pregnancy. [ABSTRACT FROM AUTHOR]

Background. The association studies of killer cell immunoglobulin-like receptors (KIRs) with the occurrence of myelodysplastic syndromes (MDS) are limited worldwide; this study investigated the genetic risk/protective factors of MDS in KIR and human leucocyte antigen (HLA) systems to gain a better understanding of the role played by KIR and their cognate HLA ligands in MDS pathogenesis. Methods. We genotyped a total number of 77 patients with MDS from Chinese Southern Han and 745 healthy controls for the KIR loci and HLA class I. The carrier frequencies of KIR genes, KIR genotypes, class I HLA ligands, and KIR-HLA combinations were calculated by direct counting. The effect of individual KIR genes and HLA ligands on MDS risk was evaluated by logistic regression analyses using SAS 9.2 software. Results. We found that neither the KIR genes nor the KIR genotypes were associated with the occurrence of MDS. However, we observed that the frequencies for the strong inhibitory ligand HLA-Bw4 as well as KIR3DL1-HLA-Bw4 combination were significantly higher in healthy controls than those in the MDS patient group, respectively (73.42% vs. 62.34%, P = 0.038 ; 70.87% vs. 59.74%, P = 0.043). Conclusion. Our results showed that HLA-Bw4 ligand and KIR3DL1-HLA-Bw4 combination could confer a protective effect against MDS in Chinese Southern Han. [ABSTRACT FROM AUTHOR]

A novel variant of HLA‐DQB1*03 differs from DQB1*03:02:01:01 by one nucleotide substitution in Exon 2. [ABSTRACT FROM AUTHOR]

HLA‐DPB1*1104:01 differs from HLA‐DPB1*540:01 by a single nucleotide change in exon 2. [ABSTRACT FROM AUTHOR]

HLA‐A*30:140 differs from HLA‐A*30:01:01 by one nucleotide change in exon 2 at position 341 (C > A). [ABSTRACT FROM AUTHOR]

The HLA‐DPA1*02:33 allele differs from DPA1*02:02:02:04 by two nucleotide change in exon 4. [ABSTRACT FROM AUTHOR]

B*46:01:33 differs from B*46:01:01:01 by one nucleotide change at nucleotide 105 in exon 2 from C to T. [ABSTRACT FROM AUTHOR]

Abstract MicroRNA (miR) is important regulators of gene expression, and aberrant miR expression has been linked to oncogenesis; however, little is understood about their contribution to colorectal cancer (CRC). Here, we determined that miR-23a is overexpressed in human colorectal cancer cell lines and tissues compared with that of normal cells. The stable over-expression of miR-23a in CRC cells was sufficient to promote cell proliferation in vitro and in vivo. Further studies showed that miR-23a can directly bind to the 3′untranslated region (3′UTR) of PDK4 mRNA and subsequently repress both the mRNA and protein expressions of PDK4. PDK4 negatively regulate CRC proliferation via suppressing PDH activity. Ectopic expression of PDK4 by transiently transfected with PDK4 vector encoding the entire coding sequence could reverse the effects of miR-23a on CRC proliferation. By this way, miR-23a promotes PDH activation and oxidative phosphorylation to generate sufficient ATP for cell proliferation. Our results illustrated that the up-regulation of miR-23a played an important role in CRC cell proliferation through direct repressing PDK4, suggesting a potential application of miR-23a in prognosis prediction and therapeutic application in CRC. Highlights • miR-23a is overexpressed in CRC cell lines and tissues compared with that of normal cells. • miR-23a repress both the mRNA and protein expressions of PDK4. • PDK4 negatively regulate CRC proliferation via suppressing PDH activity. • miR-23a facilitates PDH activation and oxidative phosphorylation via targeting PDK4. • miR-23a promotes CRC cells proliferation in vitro and in vivo via targeting PDK4. [ABSTRACT FROM AUTHOR]

HLA‐A*24:02:78 differs from HLA‐A*24:02:01:01 in exon 3 by a single nucleotide. [ABSTRACT FROM AUTHOR]

HLA‐DQB1*06:01:22 differs from HLA‐DQB1*06:01:01:01 by one nucleotide substitution in codon 189 in exon 4. [ABSTRACT FROM AUTHOR]

The novel KIR2DL4*036 allele differs from the closest allele KIR2DL4*00102 by a single missense mutation. [ABSTRACT FROM AUTHOR]

The novel KIR3DL1*00702 allele differs from the closest allele KIR3DL1*00701 by a single silent mutation. [ABSTRACT FROM AUTHOR]

The novel KIR2DS2*022 allele differs from the closest allele KIR2DS2*00101 by a single nonsynonymous mutation. [ABSTRACT FROM AUTHOR]

One nucleotide substitution in codon 189 of HLA‐C*01:02:01:01 results in a novel allele, HLA‐C*01:179. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation is a widely used and effective therapy for hematopoietic malignant diseases and numerous other disorders. High-resolution human leukocyte antigen (HLA) haplotype frequency distributions not only facilitate individual donor searches but also determine the probability with which a particular patient can find HLA-matched donors in a registry. The frequencies of the HLA-A, -B, -C, -DRB1, and -DQB1 alleles and haplotypes were estimated among 169,995 Chinese volunteers using the sequencing-based typing (SBT) method. Totals of 191 HLA-A, 244 HLA-B, 146 HLA-C, 143 HLA-DRB1 and 47 HLA-DQB1 alleles were observed, which accounted for 6.98%, 7.06%, 6.46%, 9.11% and 7.91%, respectively, of the alleles in each locus in the world (IMGT 3.16 Release, Apr. 2014). Among the 100 most common haplotypes from the 169,995 individuals, nine distinct haplotypes displayed significant regionally specific distributions. Among these, three were predominant in the South China region (i.e., the 20th, 31st, and 81sthaplotypes), another three were predominant in the Southwest China region (i.e., the 68th, 79th, and 95th haplotypes), one was predominant in the South and Southwest China regions (the 18th haplotype), one was relatively common in the Northeast and North China regions (the 94th haplotype), and one was common in the Northeast, North and Northwest China (the 40th haplotype). In conclusion, this is the first to analyze high-resolution HLA diversities across the entire country of China, based on a detailed and complete data set that covered 31 provinces, autonomous regions, and municipalities. Specifically, we also evaluated the HLA matching probabilities within and between geographic regions and analyzed the regional differences in the HLA diversities in China. We believe that the data presented in this study might be useful for unrelated HLA-matched donor searches, donor registry planning, population genetic studies, and anthropogenesis studies. [ABSTRACT FROM AUTHOR]

The novel KIR2DL4*038 allele differs from the closest allele KIR2DL4*00102 by a single missense mutation. [ABSTRACT FROM AUTHOR]

The novel KIR2DL4*037 allele differs from the closest allele KIR2DL4*00501 by a single missense mutation. [ABSTRACT FROM AUTHOR]

The novel KIR2DL4*00603 allele differs from the closest allele KIR2DL4*00602 by a silent mutation. [ABSTRACT FROM AUTHOR]

The novel KIR3DL3*063 allele differs from the closest allele KIR3DL3*04802 by a single missense mutation. [ABSTRACT FROM AUTHOR]

The novel KIR3DL3*062 allele differs from the closest allele KIR3DL3*02602 by a single missense mutation. [ABSTRACT FROM AUTHOR]

The novel KIR3DL3*02602 allele differs from the closest allele KIR3DL3*02601 by a single silent mutation. [ABSTRACT FROM AUTHOR]

Abstract: Thrombolytic agent is increasingly being used in treating acute ischemic stroke. A novel protease with strong thrombolytic activity, Neanthes japonica (Iznka) fibrinolytic enzyme (NJF) discovered in our laboratory has been reported with characteristics of direct hydrolyzing fibrin and fibrinogen. The neuroprotective effect of NJF and urokinase (UK) was tested in rat models of middle cerebral artery occlusion (MCAO). The model was successfully produced by introducing an intraluminal suture into the left middle cerebral artery (MCA). NJF (0.25, 0.5, 1mg/kg) was injected intravenously 1h after the onset of reperfusion. Compared with vehicle group, MCAO animals treated with NJF showed dose dependent reduction in cerebral infarction with improved neurological outcome. Meanwhile, ischemia induced cerebral edema was reduced in a dose dependent manner. Treatment with NJF at 0.5mg/kg was almost equivalent to UK at 15,000U/kg dosage in the reduction of cerebral infarction and cerebral edema. Biomedical assay showed that NJF treatment suppressed lipid peroxidation and restored superoxide dismutase (SOD) activities in brain tissue. These results suggest that NJF posses neuroprotective potential in rat MCAO and reperfusion model. Neuroprotection shown by NJF may be attributed to inhibition of lipid peroxidation, increase in endogenous antioxidant defense enzymes. [ABSTRACT FROM AUTHOR]

About 60 hydrologic changes in response to the Chi-Chi earthquake with Ms7.6 on September 21, 1999, occurred in 52 wells, including groundwater level, temperature, discharge rate, well pressure and radon, etc., in the subsurface fluid monitoring network. These response changes were mainly co-seismic, but some pre- and post-earthquake changes occurred mainly within 5 days before and after the Chi-Chi earthquake. The response changes of different wells clustering in different tectonic areas showed different features. These changes are distributed in five areas named as A, B, C, D and E. The response changes in A area with short hypo-central distance (less than 550 km) were mainly pre-earthquake changes occurring more than 5 days before the event. Those in area B (in Huanan tectonic block) and C (in Huabei tectonic block) were mainly co-seismic changes. The hypo-central distance is about 1100–1280 and 800–1160 km, respectively. These changes were high-frequency water-level oscillations induced by seismic waves and accompanied by prominent and permanent water-level jumps and drops. There are also some post-seismic changes including discharge rate and water radon and well pressure changes in area C. Those in area D in the Yanshan tectonic block were mainly co-seismic and post-seismic changes including water level, water temperature, and water radon concentration, etc., showing prominent and permanent water-level jumps and drops and rising concentrations of water radon. The hypo-central distance is about 1750–2060 km. Those in Area E were mainly co-seismic changes showing prominent and permanent water-level jump. The hypo-central distance is about 1810–2120 km. Three moderate earthquakes occurred in area D and one strong earthquake occurred in area E 4 months after the Chi-Chi earthquake. The different features of the response changes might be caused by the changes of local hydrologic conditions (like permeability) induced by seismic waves. On the other hand, these response changes might indicate the near-critical conditions in the area where the response changes clustered. Such changes might be understood by the crustal buckling hypothesis. It is thought that the response changes might be a kind of precursor that implies elevated earthquake risk in the region. [Copyright &y& Elsevier]

Background: The null phenotype in P1PK blood group, known as "p," is extremely rare in the whole world. Individuals of p phenotype spontaneously form anti-PP1P K isoantibody. Here, we report a case of p phenotype with naturally occurring anti-PP1P K isoantibodies in a Chinese individual., Study Design and Methods: Serology tests, containing alloantibodies screening and identification, were conducted to demonstrate the phenotype in P1PK blood group. The genotype of A4GALT gene was identified by haplotypes separation and sequencing., Results: The serological assay demonstrated the p phenotype of the proband, presenting with 1:64 titer of anti-PP1P K . The sequencing data revealed a compound heterozygote consisting of A4GALT*P1.01 with c.343A>T and a novel allele based on A4GALT*01N.05 with an addition polymorphism c.100G>A. The sequence of the novel allele has been submitted to GenBank and the accession number OM912503 was assigned., Conclusion: Our study demonstrates a case of naturally occurring anti-PP1Pk in a Chinese individual with p phenotype, which is based on compound heterozygosity including one novel allele. As the proband is a young lady, monitoring the titer of anti-PP1P K and early initiation of medical intervention are essential after her pregnancy., (© 2022 AABB.)

The Wiskott-Aldrich syndrome protein and SCAR homolog (WASH), an actin nucleation-promoting factor, is present in the nucleus where it regulates gene transcription and maintains nuclear organization. Here, we show that WASH interacts with core non-homologous end-joining (NHEJ) factors including Ku70/Ku80 and DNA-PKcs, and Ku70/Ku80 is involved in the recruitment of WASH to the sites of DNA double-stranded break (DSB). WASH depletion leads to increased cell sensitivity and impaired DNA repair capacity in response to etoposide-induced DSBs and reduces NHEJ efficiency. Mechanistically, we show that loss of WASH inhibits the phosphorylation of DNA-PKcs, H2AX, and KAP1 after DSB induction and reduces chromatin relaxation and the recruitment of several downstream NHEJ factors to DSBs. Moreover, WASH role in DSB repair depends on its conserved C-terminal VCA domain and Arp2/3 activation. Our findings reveal a function and mechanistic insight for WASH in DNA DSB repair by the NHEJ pathway., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Strong associations between HLA alleles and infectious and autoimmune diseases are well established. Although obesity is also associated with these diseases, the relationship between HLA and obesity has not been systematically investigated in a large cohort. In the current study, we analyzed the association of HLA alleles with BMI using data from 1.3 million healthy adult donors from the Chinese Marrow Donor Program (CMDP). We found 23 HLA alleles, including 12 low-resolution and 11 high-resolution alleles, were significantly associated with BMI after correction for multiple testing. Alleles associated with high BMI were enriched in haplotypes that were common in both Chinese and European populations, whereas the alleles associated with low BMI were enriched in haplotypes common only in Asians. Alleles B*07, DRB1*07, DRB1*12, and C*03:02 provided the strongest associations with BMI ( P = 6.89 × 10 -10 , 1.32 × 10 -9 , 1.52 × 10 -9 , and 4.45 × 10 -8 , respectively), where B*07 and DRB1*07 also had evidence for sex-specific effects ( P heterogeneity = 0.0067 and 0.00058, respectively). These results, which identify associations between alleles of HLA-B , DRB1 , and C with BMI in Chinese young adults, implicate a novel biological connection between HLA alleles and obesity., (© 2018 by the American Diabetes Association.)

The pentameric WASH complex is best known for its role in regulating receptor trafficking from retromer-rich endosomal subdomains. FAM21 functions to stabilize the WASH complex through its N-terminal head domain and localizes it to endosomes by directly binding the retromer through its extended C-terminal tail. Herein, we used affinity purification combined with mass spectrometry to identify additional FAM21-interacting proteins. Surprisingly, multiple components of the nuclear factor κB (NF-κB) pathway were identified, including the p50 and p65 (RelA) NF-κB subunits. We show that FAM21 interacts with these components and regulates NF-κB-dependent gene transcription at the level of p65 chromatin binding. We further demonstrate that FAM21 contains a functional monopartite nuclear localization signal sequence (NLS) as well as a CRM1/exportin1-dependent nuclear export signal (NES), both of which work jointly with the N-terminal head domain and C-terminal retromer recruitment domain to regulate FAM21 cytosolic and nuclear subcellular localization. Finally, our findings indicate that FAM21 depletion sensitizes pancreatic cancer cells to gemcitabine and 5-fluorouracil. Thus, FAM21 not only functions as an integral component of the cytoplasmic WASH complex, but also modulates NF-κB gene transcription in the nucleus., (© 2015. Published by The Company of Biologists Ltd.)