Haploinsufficiency of SAMD9L, an Endosome Fusion Facilitator, Causes Myeloid Malignancies in Mice Mimicking Human Diseases with Monosomy 7

SummaryMonosomy 7 and interstitial deletion of 7q (−7/7q−) are well-recognized nonrandom chromosomal abnormalities frequently found among patients with myelodysplastic syndromes (MDSs) and myeloid leukemias. We previously identified candidate myeloid tumor suppressor genes (SAMD9, SAMD9-like = SAMD9L, and Miki) in the 7q21.3 subband. We established SAMD9L-deficient mice and found that SAMD9L+/− mice as well as SAMD9L−/− mice develop myeloid diseases resembling human diseases associated with −7/7q−. SAMD9L-deficient hematopoietic stem cells showed enhanced colony formation potential and in vivo reconstitution ability. SAMD9L localizes in early endosomes. SAMD9L-deficient cells showed delays in homotypic endosome fusion, resulting in persistence of ligand-bound cytokine receptors. These findings suggest that haploinsufficiency of SAMD9L and/or SAMD9 gene(s) contributes to myeloid transformation

Self-Contained Induction of Neurons from Human Embryonic Stem Cells

BACKGROUND: Neurons and glial cells can be efficiently induced from mouse embryonic stem (ES) cells in a conditioned medium collected from rat primary-cultured astrocytes (P-ACM). However, the use of rodent primary cells for clinical applications may be hampered by limited supply and risk of contamination with xeno-proteins. METHODOLOGY/PRINCIPAL FINDINGS: We have developed an alternative method for unimpeded production of human neurons under xeno-free conditions. Initially, neural stem cells in sphere-like clusters were induced from human ES (hES) cells after being cultured in P-ACM under free-floating conditions. The resultant neural stem cells could circumferentially proliferate under subsequent adhesive culture, and selectively differentiate into neurons or astrocytes by changing the medium to P-ACM or G5, respectively. These hES cell-derived neurons and astrocytes could procure functions similar to those of primary cells. Interestingly, a conditioned medium obtained from the hES cell-derived astrocytes (ES-ACM) could successfully be used to substitute P-ACM for induction of neurons. Neurons made by this method could survive in mice brain after xeno-transplantation. CONCLUSION/SIGNIFICANCE: By inducing astrocytes from hES cells in a chemically defined medium, we could produce human neurons without the use of P-ACM. This self-serving method provides an unlimited source of human neural cells and may facilitate clinical applications of hES cells for neurological diseases

Methylprednisolone sodium succinate reduces spinal cord swelling but does not affect recovery of dogs with surgically treated thoracolumbar intervertebral disk herniation

The effect of methylprednisolone sodium succinate (MPSS) therapy was studied in 50 dogs with surgically treated Hansen type I thoracolumbar intervertebral disk herniation (TL-IVDH). Administration of MPSS significantly reduced the swelling of the spinal cord. The sensitivity of localization of disk extrusion using myelography in the MPSS group was 92.3%, and in the non-administration group was 83.3%. No significant difference in recovery rate or length of recovery time was found between the two groups. Administration of MPSS reduced spinal cord swelling, but has no effect on recovery in dogs after surgery for TL-IVDH

Chaotic dynamics in a flexible exchange rate system:A study of noise effects

In this paper, we investigate by means of analytical method and numerical simulations the properties of three-dimensional business cycle model, in which foreign exchange rate is flexible and a parameter is fluctuated by noise. The model is a discrete time version of Asada (Journal of Economics, 62, 239–269,1995)'s continuous time open economy model without noise. We show (1) noise may suppress the burst of flexible foreign exchange rate when its behavior begins to burst as a bifurcation parameter (adjustment speed of the goods market) is increased, (2) the windows of cycles can be broken by noise, and (3) noise may reveal the hidden structures

Re-estimating per Capita Individual Consumption by Age from Household Data

Mori and Inaba proposed an estimation method of deriving individual consumption by age from macro data classified by age of household head (HH), using quadratic programming, 1997. We replaced their approach by regression with weights which are determined by the magnitude of standardized residuals, following the leads of Huber, 1981 and Minotani, 1992. Using our revised method which provides objective statistics, the estimates of per capita individual consumption of fresh fruit and fresh fish, respectively, by non-adults are substantially larger and those for the young adults somewhat smaller in our studies than in previous studies. It seems quite apparent that Japanese children and young adults have decreased their at-home consumption of these products substantially in recent years. Those older than 50years of age seem to have maintained their consumption at relatively high levels