Enhanced x-ray emission coinciding with giant radio pulses from the Crab Pulsar.

Giant radio pulses (GRPs) are sporadic bursts emitted by some pulsars that last a few microseconds and are hundreds to thousands of times brighter than regular pulses from these sources. The only GRP-associated emission outside of radio wavelengths is from the Crab Pulsar, where optical emission is enhanced by a few percentage points during GRPs. We observed the Crab Pulsar simultaneously at x-ray and radio wavelengths, finding enhancement of the x-ray emission by 3.8 ± 0.7% (a 5.4σ detection) coinciding with GRPs. This implies that the total emitted energy from GRPs is tens to hundreds of times higher than previously known. We discuss the implications for the pulsar emission mechanism and extragalactic fast radio bursts.

Microbiome Alteration in Type 2 Diabetes Mellitus Model of Zebrafish.

Understanding the gut microbiota in metabolic disorders, including type 2 diabetes mellitus (T2DM), is now gaining importance due to its potential role in disease risk and progression. We previously established a zebrafish model of T2DM, which shows glucose intolerance with insulin resistance and responds to anti-diabetic drugs. In this study, we analysed the gut microbiota of T2DM zebrafish by deep sequencing the 16S rRNA V3-V4 hypervariable regions, and imputed a functional profile using predictive metagenomic tools. While control and T2DM zebrafish were fed with the same kind of feed, the gut microbiota in T2DM group was less diverse than that of the control. Predictive metagenomics profiling using PICRUSt revealed functional alternation of the KEGG pathways in T2DM zebrafish. Several amino acid metabolism pathways (arginine, proline, and phenylalanine) were downregulated in the T2DM group, similar to what has been previously reported in humans. In summary, we profiled the gut microbiome in T2DM zebrafish, which revealed functional similarities in gut bacterial environments between these zebrafish and T2DM affected humans. T2DM zebrafish can become an alternative model organism to study host-bacterial interactions in human obesity and related diseases.

A Comprehensive Review of Our Current Understanding of Red Blood Cell (RBC) Glycoproteins.

Human red blood cells (RBC), which are the cells most commonly used in the study of biological membranes, have some glycoproteins in their cell membrane. These membrane proteins are band 3 and glycophorins A-D, and some substoichiometric glycoproteins (e.g., CD44, CD47, Lu, Kell, Duffy). The oligosaccharide that band 3 contains has one N-linked oligosaccharide, and glycophorins possess mostly O-linked oligosaccharides. The end of the O-linked oligosaccharide is linked to sialic acid. In humans, this sialic acid is N-acetylneuraminic acid (NeuAc). Another sialic acid, N-glycolylneuraminic acid (NeuGc) is present in red blood cells of non-human origin. While the biological function of band 3 is well known as an anion exchanger, it has been suggested that the oligosaccharide of band 3 does not affect the anion transport function. Although band 3 has been studied in detail, the physiological functions of glycophorins remain unclear. This review mainly describes the sialo-oligosaccharide structures of band 3 and glycophorins, followed by a discussion of the physiological functions that have been reported in the literature to date. Moreover, other glycoproteins in red blood cell membranes of non-human origin are described, and the physiological function of glycophorin in carp red blood cell membranes is discussed with respect to its bacteriostatic activity.

Structure of a sialo-oligosaccharide from glycophorin in carp red blood cell membranes.

We isolated a high-purity carp glycophorin from carp erythrocyte membranes and prepared the oligosaccharide fraction from glycophorin by ß-elimination [1]. The oligosaccharide fraction was separated into two components (P-1 and P-2) using a Glyco-Pak DEAE column. These O-linked oligosaccharides (P-1 and P-2) were composed of glucose, galactose, fucose, N-acetylgalactosamine and N-glycolylneuraminic acid (NeuGc). The P-1 and P-2 contained one and two NeuGc residues, respectively, and the P-1 exhibited bacteriostatic activity [1]. Using NMR and GC-MS, we determined that the structure of the bacteriostatic P-1 was NeuGcα2→6 (Fucα1→4) (Glcα1→3) Galß1→4GalNAc-ol. This O-linked oligosaccharide was unique for a vertebrate with respect to the hexosamine and hexose linkages and its non-chain structure.

Isolation and characterization of glycophorin from carp red blood cell membranes.

We isolated a high-purity carp glycophorin from carp erythrocyte membranes following extraction using the lithium diiodosalicylate (LIS)-phenol method and streptomycin treatment. The main carp glycophorin was observed to locate at the position of the carp and human band-3 proteins on an SDS-polyacrylamide gel. Only the N-glycolylneuraminic acid (NeuGc) form of sialic acid was detected in the carp glycophorin. The oligosaccharide fraction was separated into two components (P-1 and P-2) using a Glyco-Pak DEAE column. We observed bacteriostatic activity against five strains of bacteria, including two known fish pathogens. Fractions from the carp erythrocyte membrane, the glycophorin oligosaccharide and the P-1 also exhibited bacteriostatic activity; whereas the glycolipid fraction and the glycophorin fraction without sialic acid did not show the activity. The carp glycophorin molecules attach to the flagellum of V. anguillarum or the cell surface of M. luteus and inhibited bacterial growth.

Decreased factor XIII activity in a patient with subcutaneous bleeding after double filtration plasmapheresis.

Double filtration plasmapheresis (DFPP) is often performed as a treatment for autoimmune diseases including pemphigus vulgaris. We report a pemphigus vulgaris patient with subcutaneous bleeding, gradually spreading over a period of 10 days after DFPP. In this patient, factor XIII activity was markedly decreased. In three other patients, factor XIII activities were markedly reduced the day following DFPP, were but restored by days 7-10. From these findings, subcutaneous bleeding may have occurred in the present patient due to a delayed recovery of the decreased factor XIII activity after DFPP. Therefore, decreased factor XIII activity could be a critical cause of subcutaneous bleeding after DFPP.

Efficacy of granulocyte and monocyte adsorption apheresis for pustular psoriasis.

Granulocyte and monocyte adsorption apheresis (GCAP) has recently shown remarkable effects on ulcerative colitis, which is characterized by inflammation and neutrophil infiltration. Pustular psoriasis often shows histological findings of neutrophilic pustules in the epidermis, and in Japan is usually treated with etretinate or immunosuppressive agents. However, there are some resistant cases to these therapies. We performed GCAP on one patient with generalized pustular psoriasis (patient 1) and on one patient with acrodermatitis continua, a subtype of pustular psoriasis limited to acral lesions (patient 2). Patient 1, a 44-year-old woman suffering from alcoholic liver cirrhosis and osteoporosis as a result of the liver cirrhosis, received two GCAP sessions because cyclosporine was ineffective. Patient 2, a 66-year-old man with hypertension who had suffered from a brain infarction 4 years before, had five GCAP sessions because etretinate was ineffective. GCAP remarkably improved the skin lesions in both patients. No adverse effects were observed either during or after treatment. From these findings, GCAP could be an effective therapy for refractory cases of pustular psoriasis.

Efficacy of granulocyte and monocyte adsorption apheresis for three cases of refractory pyoderma gangrenosum.

Pyoderma gangrenosum presents with chronic skin ulcers and is histologically characterized by neutrophil infiltration throughout the dermis. It is also occasionally associated with ulcerative colitis, a type of inflammatory bowel disease, against which granulocyte and monocyte adsorption apheresis (GCAP) has recently shown remarkable efficacy. We performed GCAP on three refractory cases of pyoderma gangrenosum with painful bilateral leg ulcers and hereby report the results obtained. Patient 1 was a 43-year-old woman with a four-year history of recurrent painful skin ulcers treated with prednisolone and cyclosporine. Patient 2 was a 29-year-old woman who had been suffering from pyoderma gangrenosum with severe pain for two weeks, associated with an 11-year history of ulcerative colitis treated with prednisolone and salazosulfapyridine. Patient 3 was a 63-year-old man with a three-year history of recurrent ulcers with pain, suffering from rheumatoid arthritis treated with prednisolone and cyclophosphamide. The sizes of the lesions were reduced in all three patients following a weekly GCAP treatment for 10 or 11 consecutive weeks, and the re-epithelialization of ulcers were additionally observed in two patients. The pain disappeared dramatically in all three patients following two sessions of GCAP therapy. No adverse effects were observed for up to at least eight months after treatment. We therefore considered GCAP as one effective alternative to currently existing therapies, with regards to refractory cases of pyoderma gangrenosum.

Antibody titers to desmogleins 1 and 3 in a patient with paraneoplastic pemphigus associated with follicular dendritic cell sarcoma.

BACKGROUND: Most paraneoplastic pemphigus (PNP) cases reported to date have been associated with lymphoproliferative neoplasms. Patients with PNP have autoantibodies against the plakin family (eg, envoplakin and periplakin). Antibodies against desmoglein 3 (Dsg3) and Dsg1, antigens for classic types of pemphigus, have also been reported to play an important role in the initial stage of PNP. OBSERVATIONS: We describe a patient with PNP associated with follicular dendritic cell sarcoma. Antibodies to envoplakin and periplakin were detected. When only mucosal lesions were observed at the early stage, the antibody to Dsg3 but not to Dsg1 was detected by enzyme-linked immunosorbent assay. After skin lesions appeared, antibodies to Dsg1 and Dsg3 were detected. These titers were elevated, with exacerbation of skin lesions. Although the patient received corticosteroid therapy, double-filtration plasmapheresis, and intravenous human immunoglobulin therapy after surgical resection of follicular dendritic cell sarcoma, she died of fungal infective lung embolisms. A direct immunofluorescence study of autopsy samples showed IgG deposition in the epidermis of the skin and oral mucosal membrane, but not in the lungs and kidneys and follicular dendritic cell sarcoma of the para-aortic area. CONCLUSION: In this patient with PNP and follicular dendritic cell sarcoma, there was an association between the clinical phenotype and the anti-Dsg antibody profile, as seen in pemphigus vulgaris.

A cathepsin B-like enzyme from mackerel white muscle is a precursor of cathepsin B.

A cathepsin B-like enzyme from the white muscle of common mackerel Scomber japonicus was a cysteine protease that hydrolyzed Z-Arg-Arg-MCA, the substrate for cathepsin B. In a partial purified cathepsin B-like enzyme preparation at 4 degrees C left over time, a converted enzyme that hydrolyzes Z-Arg-Arg-MCA and Z-Phe-Arg-MCA appeared in the preparation. The converted enzyme was purified from the cathepsin B-like enzyme, characterized and was identified as mackerel cathepsin B. These results suggested that the mackerel cathepsin B-like enzyme was a precursor of cathepsin B. Mackerel cathepsin B formed in the purified cathepsin B-like enzyme preparation by adding of a small amount of the purified cathepsin B to the preparation. Therefore, mackerel cathepsin B-like enzyme was converted to the mature form of cathepsin B by autoactivation. The conversion of the cathepsin B-like enzyme (molecular mass 60 kDa) to cathepsin B (molecular mass 23 kDa) was detected by immunoblotting by using human anti-(cathepsin B) antibody. The intermediate forms of 40 kDa and 38 kDa were also detected during the conversion.