Discovery of a New Deeply Eclipsing SU UMa-Type Dwarf Nova, IY UMa (= TmzV85)

We discovered a new deeply eclipsing SU UMa-type dwarf nova, IY UMa, which experienced a superoutburst in 2000 January. Our monitoring revealed two distinct outbursts, which suggest a superoutburst interval of ~800 d, or its half, and an outburst amplitude of 5.4 mag. From time-series photometry during the superoutburst, we determined a superhump and orbital period of 0.07588 d and 0.0739132 d, respectively.Comment: 5 pages, 3 figures, accepted by PASJ lette

Life-Changing Decisions: Exploring Proximal and Distal Motivations Behind Why American Parents Adopt Domestically or Internationally

The purpose of this qualitative study was to explore American parents proximal and distal motivations for choosing domestic and international adoption from the distinctive viewpoint of adoptive parents own words and perspectives using the lenses of culture and social exchange theory The findings from this study revealed three primary factors that were found to influence adoptive parents motivations to choose domestic or international adoption 1 unique cultural influences on domestic and international adoptive parents adoption motivations 2 shared similarities and discrepant differences between adoptive parents motivations who adopted domestically or internationally and 3 perceived intrinsic and extrinsic costs and rewards that influenced parents adoption motivations A conceptual decision-making model is introduced to illustrate the complicated calculus behind American parents motivations to choose either domestic or international adoption Suggestions for adoption regulation adoption process and recruitment efforts for both domestic and international adoptions are discusse

A New SU UMa-Type Dwarf Nova, QW Serpentis (= TmzV46)

We report on the results of the QW Ser campaign which has been continued from 2000 to 2003 by the VSNET collaboration team. Four long outbursts and many short ones were caught during this period. Our intensive photometric observations revealed superhumps with a period of 0.07700(4) d during all four superoutbursts, proving the SU UMa nature of this star. The recurrence cycles of the normal outbursts and the superoutbursts were measured to be $\sim$50 days and 240(30) days, respectively. The change rate of the superhump period was -5.8x10^{-5}. The distance and the X-ray luminosity in the range of 0.5-2.4 keV are estimated to be 380(60) pc and log L_x = 31.0 \pm 0.1 erg s^{-1}. These properties have typical values for an SU UMa-type dwarf nova with this superhump period.Comment: 9 pages, 12 figures, to appear in the VSNET special issue of PAS

Photometric study of new southern SU UMa-type dwarf novae and candidates: V877 Ara, KK Tel and PU CMa

We photometrically observed three dwarf novae V877 Ara, KK Tel and PU CMa. We discovered undisputed presence of superhumps in V877 Ara and KK Tel, with mean periods of 0.08411(2) d and 0.08808(3) d, respectively. Both V877 Ara and KK Tel are confirmed to belong to long-period SU UMa-type dwarf novae. In V877 Ara, we found a large decrease of the superhump period (dot(P)/P = -14.5 +/- 2.1 x 10^(-5)). There is evidence that the period of KK Tel decreased at a similar or a more exceptional rate. Coupled with the past studies of superhump period changes, these findings suggest that a previously neglected diversity of phenomena is present in long-period SU UMa-type dwarf novae. The present discovery of a diversity in long-period SU UMa-type systems would become an additional step toward a full understanding the dwarf nova phenomenon. PU CMa is shown to be an excellent candidate for an SU UMa-type dwarf nova. We examined the outburst properties of these dwarf novae, and derived characteristic outburst recurrence times. Combined with the recently published measurement of the orbital period of PU CMa, we propose that PU CMa is the first object filling the gap between the extreme WZ Sge-type and ER UMa-type stars.Comment: 12 pages, 14 figures, accepted for publication in MNRA

Small Extracellular Vesicles from Peripheral Blood of Aged Mice Pass the Blood-Brain Barrier and Induce Glial Cell Activation

Extracellular vesicles (EVs), including small EVs (sEVs), are involved in neuroinflammation and neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Yet, increased neuroinflammation can also be detected in the aging brain, and it is associated with increased glial activation. Changes in EV concentration are reported in aging tissues and senescence cells, suggesting a role of EVs in the process of aging. Here, we investigated the effect of peripheral sEVs from aged animals on neuroinflammation, specifically on glial activation. sEVs were isolated from the peripheral blood of young (3 months) and aged (24 months) C57BL/6J wildtype mice and injected into the peripheral blood from young animals via vein tail injections. The localization of EVs and the expression of selected genes involved in glial cell activation, including Gfap , Tgf- β , Cd68 , and Iba1 , were assessed in brain tissue 30 min, 4 h, and 24 h after injection. We found that sEVs from peripheral blood of aged mice but not from young mice altered gene expression in the brains of young animals. In particular, the expression of the specific astrocyte marker, Gfap , was significantly increased, indicating a strong response of this glial cell type. Our study shows that sEVs from aged mice can pass the blood-brain barrier (BBB) and induce glial cell activation

Systemic Exosomal Delivery of shRNA Minicircles Prevents Parkinsonian Pathology

The development of new therapies to slow down or halt the progression of Parkinson's disease is a health care priority. A key pathological feature is the presence of alpha-synuclein aggregates, and there is increasing evidence that alpha-synuclein propagation plays a central role in disease progression. Consequently, the downregulation of alpha-synuclein is a potential therapeutic target. As a chronic disease, the ideal treatment will be minimally invasive and effective in the long-term. Knockdown of gene expression has clear potential, and siRNAs specific to alpha-synuclein have been designed; however, the efficacy of siRNA treatment is limited by its short-term efficacy. To combat this, we designed shRNA minicircles (shRNA-MCs), with the potential for prolonged effectiveness, and used RVG-exosomes as the vehicle for specific delivery into the brain. We optimized this system using transgenic mice expressing GFP and demonstrated its ability to downregulate GFP protein expression in the brain for up to 6 weeks. RVG-exosomes were used to deliver anti-alpha-synuclein shRNA-MC therapy to the alpha-synuclein preformed-fibril-induced model of parkinsonism. This therapy decreased alpha-synuclein aggregation, reduced the loss of dopaminergic neurons, and improved the clinical symptoms. Our results confirm the therapeutic potential of shRNA-MCs delivered by RVG-exosomes for long-term treatment of neurodegenerative diseases

Efficient Non-viral Gene Delivery into Human Hematopoietic Stem Cells by Minicircle Sleeping Beauty Transposon Vectors

The Sleeping Beauty (SB) transposon system is a non-viral gene delivery platform that combines simplicity, inexpensive manufacture, and favorable safety features in the context of human applications. However, efficient correction of hematopoietic stem and progenitor cells (HSPCs) with non-viral vector systems, including SB, demands further refinement of gene delivery techniques. We set out to improve SB gene transfer into hard-to-transfect human CD34 + cells by vectorizing the SB system components in the form of minicircles that are devoid of plasmid backbone sequences and are, therefore, significantly reduced in size. As compared to conventional plasmids, delivery of the SB transposon system as minicircle DNA is 3c20 times more efficient, and it is associated with up to a 50% reduction in cellular toxicity in human CD34 + cells. Moreover, providing the SB transposase in the form of synthetic mRNA enabled us to further increase the efficacy and biosafety of stable gene delivery into hematopoietic progenitors ex vivo. Genome-wide insertion site profiling revealed a close-to-random distribution of SB transposon integrants, which is characteristically different from gammaretroviral and lentiviral integrations in HSPCs. Transplantation of gene-marked CD34 + cells in immunodeficient mice resulted in long-term engraftment and hematopoietic reconstitution, which was most efficient when the SB transposase was supplied as mRNA and nucleofected cells were maintained for 4\u20138 days in culture before transplantation. Collectively, implementation of minicircle and mRNA technologies allowed us to further refine the SB transposon system in the context of HSPC gene delivery to ultimately meet clinical demands of an efficient and safe non-viral gene therapy protocol. Ivics and collegues refined the Sleeping Beauty transposon system for gene transfer in human hematopoietic stem and progenitor cells by vectorizing the transposon components as minicircle DNA and synthetic mRNA. The advanced vector system enables efficient and safe non-viral engineering of hematopoietic cells that can be transplanted into immunodeficient mice