Alterations in erythrocyte membrane lipid and its fragility in a patient with familial lecithin : cholesterol acyltrasferase (LCAT) deficiency

Lecithin : cholesterol acyltrasferase (LCAT) plays a key role in the cholesterol metabolism-mediated esterification of free cholesterol into the cholesterol ester in normal plasma. Familial LCAT deficiency is frequently associated with anemia. Using biochemical and physiological techniques, the erythrocytes of this patient were investigated to gain an insight into the relationship between the abnormalities of lipid metabolism and erythrocyte membrane fragility. Abnormal erythrocytes, so-called Target cells and/or Knizocytes, were observed at 20% in our patient’s erythrocytes. Moreover, the mean corpuscular volume of the patient’s cells was 7% greater than that of a normal individual. In the membrane lipids of the patient’s erythrocytes, cholesterol and phosphatidylcholine increased, and phosphatidylethanolamine decreased. The electron spin resonance technique with a fatty acid spin probe showed that the membrane fluidity was more elevated than that of normal cells in spite of the increase in cholesterol content and the cholesterol/ phospholipid ratio of the membrane of patient’s erythrocytes. The patient’s abnormally shaped erythrocytes were less deformed than those of the normal individual under high shear stress. The partial depletion of membrane cholesterol from the patient’s erythrocytes was demonstrated by incubation with normal plasma with LCAT activity. The increment of transformed erythrocytes during the incubation could be prevented by cholesterol depletion from the patient’s erythrocyte membrane. These findings indicate that normochromic anemia of the patient might be caused by erythrocyte fragility resulting from decreased deformity and/or abnormal shape of the cells due to abnormal lipid composition in the membrane

Increasing vegetable intake 400 g/day can control body weight and lipid profile in overweight hyperlipidemia menopausal women

Background: Indonesia suffers growing health problems like obesity, diabetes, and other metabolic syndromes with dietary habit as one of risk factors. To control the lipid and glycaemic profile, high fibre intake has been recommended. This study administered 400g/day vegetable intake with its fiber contents and observed the effects in lipid profile and glycaemic control.Design: A parallel study of 30 pairs of menopausal women match paired in overweight, menopause, hyperlipidaemia, age, etc randomly divided into two groups (vegetable and control). The baseline data obtained from questionnaire and preliminary blood-withdrawn of consented participants, then matched the characteristics included the results of lipid profile and glycated albumin. The administration was conducted for 21days by providing 400g/day of vegetable to the vegetable group subjects. Nutrition assessments were conducted at the baseline, middle, and final period. The data were analysed by using the unpaired and paired t-test.Results: Significant results (p<0.05) were seen in biochemical variables in the lipid profile of total cholesterol, LDL cholesterol, and HDL cholesterol and body weight and BMI within the vegetable group. Significant results for the same variables were shown between vegetable and control group at the final data (p<0.05). The nutrition assessments result showed significances (p<0.05) within vegetable group and between two groups on the final data. After 21 days, significant decreases were found on the intakes of energy, lipids, carbohydrates (p<0.05), while vegetable intake and fiber intake showed significant increases (p<0.05).Conclusion: These data suggest that maintaining a healthy diet of 400 g/d vegetable can be effective in weight management and lipid profile control

Chromosome 1p36 deletion syndrome detected by NGS

Although chromosome 1p36 deletion syndrome is considered clinically recognizable based on characteristic features, the clinical manifestations of patients during infancy are often not consistent with those observed later in life. We report a 4-month-old girl who showed multiple congenital anomalies and developmental delay, but no clinical signs of syndromic disease caused by a terminal deletion in 1p36.32-p36.33 that was first identified by targeted-exome sequencing for molecular diagnosis

Functionally confirmed compound heterozygous ADAM17 missense loss-of-function variants cause neonatal inflammatory skin and bowel disease 1

A disintegrin and metalloprotease 17 (ADAM17) is the major sheddase that processes more than 80 substrates, including tumour necrosis factor-α (TNFα). The homozygous genetic deficiency of ADAM17 causing a complete loss of ADAM17 expression was reported to be linked to neonatal inflammatory skin and bowel disease 1 (NISBD1). Here we report for the first time, a family with NISBD1 caused by functionally confirmed compound heterozygous missense variants of ADAM17, namely c.1699T>C (p.Cys567Arg) and c.1799G>A (p.Cys600Tyr). Both variants were detected in two siblings with clinical features of NISBD1, such as erythroderma with exudate in whole body, recurrent skin infection and sepsis and prolonged diarrhoea. In a cell-based assay using Adam10/17 double-knockout mouse embryonic fibroblasts (Adam10/17−/− mEFs) exogenously expressing each of these mutants, phorbol 12-myristate 13-acetate-stimulated shedding was strongly reduced compared with wild-type ADAM17. Thus, in vitro functional assays demonstrated that both missense variants cause the loss-of-function of ADAM17, resulting in the development of NISBD1. Our study further expands the spectrum of genetic pathology underlying ADAM17 in NISBD1 and establishes functional assay systems for its missense variants

Fast parametric two-qubit gates with suppressed residual interaction using the second-order nonlinearity of a cubic transmon

We demonstrate fast two-qubit gates using a parity-violated superconducting qubit consisting of a capacitively shunted asymmetric Josephson-junction loop under a finite magnetic flux bias. The second-order nonlinearity manifesting in the qubit enables the interaction with a neighboring single-junction transmon qubit via first-order interqubit sideband transitions with Rabi frequencies up to 30 MHz. Simultaneously, the unwanted static longitudinal (ZZ) interaction is eliminated with ac Stark shifts induced by a continuous microwave drive near resonant to the sideband transitions. The average fidelities of the two-qubit gates are evaluated with randomized benchmarking as 0.971, 0.958, and 0.962 for CZ, iswap, and swap gates, respectively

CD153/CD30 signaling promotes age-dependent tertiary lymphoid tissue expansion and kidney injury

高齢者腎臓病を悪化させる原因細胞・分子の同定に成功. 京都大学プレスリリース. 2021-11-30.A new drug target for kidney disease. 京都大学プレスリリース. 2021-11-30.Tertiary lymphoid tissues (TLTs) facilitate local T- and B-cell interactions in chronically inflamed organs. However, the cells and molecular pathways that govern TLT formation are poorly defined. Here we identify TNF superfamily CD153-CD30 signaling between two unique age-dependent lymphocyte subpopulations, CD153⁺PD-1⁺CD4⁺ senescence-associated T (SAT) cells and CD30+T-bet+ age-associated B cells (ABCs), as a driver for TLT expansion. SAT cells, which produced ABC-inducing factors IL21 and IFNγ, and ABCs progressively accumulated within TLTs in aged kidneys after injury. Notably, in kidney injury models, CD153 or CD30 deficiency impaired functional SAT cell induction, which resulted in reduced ABC numbers and attenuated TLT formation with improved inflammation, fibrosis and renal function. Attenuated TLT formation after transplantation of CD153-deficient bone marrow further supported the importance of CD153 in immune cells. Clonal analysis revealed that SAT cells and ABCs in the kidneys arose from both local differentiation and recruitment from the spleen. In the synovium of aged rheumatoid arthritis patients, T peripheral helper/T follicular helper cells and ABCs also expressed CD153 and CD30, respectively. Together, our data reveal a previously unappreciated function of CD153-CD30 signaling in TLT formation and propose targeting CD153-CD30 signaling pathway as a therapeutic target for slowing kidney disease progression