Human Hematopoietic Stem Cells Can Survive In Vitro for Several Months

We previously reported that long-lasting in vitro hematopoiesis could be achieved using the cells differentiated from primate embryonic stem (ES) cells. Thus, we speculated that hematopoietic stem cells differentiated from ES cells could sustain long-lasting in vitro hematopoiesis. To test this hypothesis, we investigated whether human hematopoietic stem cells could similarly sustain long-lasting in vitro hematopoiesis in the same culture system. Although the results varied between experiments, presumably due to differences in the quality of each hematopoietic stem cell sample, long-lasting in vitro hematopoiesis was observed to last up to nine months. Furthermore, an in vivo analysis in which cultured cells were transplanted into immunodeficient mice indicated that even after several months of culture, hematopoietic stem cells were still present in the cultured cells. To the best of our knowledge, this is the first report to show that human hematopoietic stem cells can survive in vitro for several months

Nuclear RNA export factor 7 is localized in processing bodies and neuronal RNA granules through interactions with shuttling hnRNPs

The nuclear RNA export factor (NXF) family proteins have been implicated in various aspects of post-transcriptional gene expression. This study shows that mouse NXF7 exhibits heterologous localization, i.e. NXF7 associates with translating ribosomes, stress granules (SGs) and processing bodies (P-bodies), the latter two of which are believed to be cytoplasmic sites of storage, degradation and/or sorting of mRNAs. By yeast two-hybrid screening, a series of heterogeneous nuclear ribonucleoproteins (hnRNPs) were identified as possible binding partners for NXF7. Among them, hnRNP A3, which is believed to be involved in translational control and/or cytoplasmic localization of certain mRNAs, formed a stable complex with NXF7 in vitro. Although hnRNP A3 was not associated with translating ribosomes, it was co-localized with NXF7 in P-bodies. After exposing to oxidative stress, NXF7 trans-localized to SGs, whereas hnRNP A3 did not. In differentiated neuroblastoma Neuro2a cells, NXF7 was co-localized with hnRNP A3 in cell body and neurites. The amino terminal half of NXF7, which was required for stable complex formation with hnRNP A3, coincided with the region required for localization in both P-bodies and neuronal RNA granules. These findings suggest that NXF7 plays a role in sorting, transport and/or storage of mRNAs through interactions with hnRNP A3

Functional activity of RLIM/Rnf12 is regulated by phosphorylation-dependent nucleo-cytoplasmic shuttling

The X-linked gene Rnf12 encodes the ubiquitin ligase RLIM/Rnf12 which serves as a major sex-specific epigenetic regulator of female mouse nurturing tissues. Early during embryogenesis, RLIM/Rnf12 expressed from the maternal allele is crucial for the development of extraembryonic trophoblast cells. In contrast, in mammary glands of pregnant and lactating adult females RLIM/Rnf12 expressed from the paternal allele functions as a critical survival factor for milk producing alveolar cells. While RLIM/Rnf12 is detected mostly in the nucleus, little is known about how and in which cellular compartment(s) RLIM/Rnf12 mediates its biological functions. Here, we demonstrate that RLIM/Rnf12 protein shuttles between the nucleus and cytoplasm and that this is regulated by phosphorylation of serine S214 located within its nuclear localization sequence (NLS). We show that shuttling is important for RLIM to exert its biological functions, as alveolar cell survival activity is inhibited in shuttling-deficient nuclear or cytoplasmic RLIM/Rnf12. Thus, the regulated nucleo-cytoplasmic shuttling of RLIM/Rnf12 coordinates cellular compartments during alveolar cell survival

Refractory Right Ventricular Failure in a Patient with Emery-Dreifuss Muscular Dystrophy

A 23-year-old man had progressive muscle weakness and Emery-Dreifuss muscular dystrophy (EDMD) due to a LMNA (lamin A/C) mutation. Congestive heart failure diagnosed at 19 years of age. Maximal drug treatment/cardiac resynchronization failed to improve the cardiac function. He was therefore hospitalized due to heart failure. Despite extracorporeal membrane oxygenation, he developed severe right heart dysfunction and died (multiple organ failure). A cardiac lesion's presence determines the prognosis of EDMD. While there are many arrhythmia reports, few reports on heart failure (particularly severe heart failure requiring cardiac transplantation) have been published. Right heart function monitoring and early ventricular-assist device use plus right heart support considering heart transplantation are important

Tau isoform expression and phosphorylation in marmoset brains

Tau is a microtubule-associated protein expressed in neuronal axons. Hyperphosphorylated tau is a major component of neurofibrillary tangles, a pathological hallmark of Alzheimer’s disease (AD). Hyperphosphorylated tau aggregates are also found in many neurodegenerative diseases, collectively referred to as “tauopathies,” and tau mutations are associated with familiar frontotemporal lobar degeneration (FTLD). Previous studies have generated transgenic mice with mutant tau as tauopathy models, but non-human primates, which are more similar to humans, may be a better model to study tauopathies. For example, the common marmoset is poised as a nonhuman primate model for investigating the etiology of age-related neurodegenerative diseases. However, no biochemical studies of tau have been conducted in marmoset brains. Here, we investigated several important aspects of tau, including expression of different tau isoforms and its phosphorylation status, in the marmoset brain. We found that marmoset tau does not possess the “primate unique motif” in its N-terminal domain. We also discovered that the tau isoform expression pattern in marmosets is more similar to that of mice than of humans, with adult marmoset brains expressing only four-repeat tau isoforms as in adult mice but unlike in adult human brains. Of note, tau in brains of marmoset newborns was phosphorylated at several sites associated with AD pathology. However, in adult marmoset brains, much of this phosphorylation was lost, except for Ser-202 and Ser-404 phosphorylation. These results reveal key features of tau expression and phosphorylation in the marmoset brain, a potentially useful non-human primate model of neurodegenerative diseases

Materials and Life Science Experimental Facility (MLF) at the Japan Proton Accelerator Research Complex II: Neutron Scattering Instruments

The neutron instruments suite, installed at the spallation neutron source of the Materials and Life Science Experimental Facility (MLF) at the Japan Proton Accelerator Research Complex (J-PARC), is reviewed. MLF has 23 neutron beam ports and 21 instruments are in operation for user programs or are under commissioning. A unique and challenging instrumental suite in MLF has been realized via combination of a high-performance neutron source, optimized for neutron scattering, and unique instruments using cutting-edge technologies. All instruments are/will serve in world-leading investigations in a broad range of fields, from fundamental physics to industrial applications. In this review, overviews, characteristic features, and typical applications of the individual instruments are mentioned