Semaphorin3A-Inhibitor Ameliorates Doxorubicin-Induced Podocyte Injury

Podocyte injury is an independent risk factor for the progression of renal diseases. Semaphorin3A (SEMA3A), expressed in podocytes and tubular cells in the mammalian adult kidneys, has been reported to regulate diverse biological functions and be associated with renal diseases. Here, we investigated pathological roles of SEMA3A signaling on podocyte injury using a doxorubicin (Dox)-induced mouse model and examined the therapeutic effect of SEMA3A-inhibitor (SEMA3A-I). We demonstrated that Dox caused massive albuminuria and podocyte apoptosis as well as an increase of SEMA3A expression in podocytes, all of which were ameliorated with SEMA3A-I treatment. In addition, c-Jun N-terminal kinase (JNK), known as a downstream of SEMA3A signaling, was activated in Dox-injected mouse podocytes while SEMA3A-I treatment partially blocked the activation. In vitro, SEMA3A-I protected against Dox-induced podocyte apoptosis and recombinant SEMA3A caused podocyte apoptosis with activation of JNK signaling. JNK inhibitor, SP600125, attenuated SEMA3A-induced podocyte apoptosis, indicating that the JNK pathway would be involved in SEMA3A-induced podocyte apoptosis. Furthermore, the analysis of human data revealed a positive correlation between levels of urinary SEMA3A and protein, suggesting that SEMA3A is associated with podocyte injury. In conclusion, SEMA3A has essential roles in podocyte injury and it would be the therapeutic target for protecting from podocyte injury

Kinematic Structure of Molecular Gas around High-mass Star YSO, Papillon Nebula, in N159 East in the Large Magellanic Cloud

We present the ALMA Band 3 and Band 6 results of 12CO(2-1), 13$CO(2-1), H30alpha recombination line, free-free emission around 98 GHz, and the dust thermal emission around 230 GHz toward the N159 East Giant Molecular Cloud (N159E) in the Large Magellanic Cloud (LMC). LMC is the nearest active high-mass star forming face-on galaxy at a distance of 50 kpc and is the best target for studing high-mass star formation. ALMA observations show that N159E is the complex of filamentary clouds with the width and length of ~1 pc and 5 pc - 10 pc, respectively. The total molecular mass is 0.92 x 10^5 Msun from the 13CO(2-1) intensity. N159E harbors the well-known Papillon Nebula, a compact high-excitation HII region. We found that a YSO associated with the Papillon Nebula has the mass of 35 Msun and is located at the intersection of three filamentary clouds. It indicates that the formation of the high-mass YSO was induced by the collision of filamentary clouds. Fukui et al. 2015 reported a similar kinematic structure toward a YSO in the N159 West region which is another YSO that has the mass larger than 35 Msun in these two regions. This suggests that the collision of filamentary clouds is a primary mechanism of high-mass star formation. We found a small molecular hole around the YSO in Papillon Nebula with sub-pc scale. It is filled by free-free and H30alpha emission. Temperature of the molecular gas around the hole reaches ~ 80 K. It indicates that this YSO has just started the distruction of parental molecular cloud.Comment: 28 pages, 7 figures. Submitted to Ap

IgA Nephropathy Complicated with X-linked Thrombocytopenia

Renal involvement is occasionally observed in Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT). It has been reported that galactose-deficient IgA is a closely linked to IgA nephropathy (IgAN), suggesting that patients with XLT/WAS associated with reduced galactosylation on serum IgA are susceptible to IgAN. It is necessary to pay more attention to patients with IgAN due to the potential complication with XLT/WAS. We here present a patient of XLT complicated with mild IgAN who underwent tonsillectomy combined with steroid pulse therapy to achieve complete clinical remission

Dense Clumps in Giant Molecular Clouds in the Large Magellanic Cloud: Density and Temperature Derived from 13^{13}CO(J=3−2J=3-2) Observations

In order to precisely determine temperature and density of molecular gas in the Large Magellanic Cloud, we made observations of optically thin $^{13}$CO($J=3-2$) transition by using the ASTE 10m telescope toward 9 peaks where $^{12}$CO($J=3-2$) clumps were previously detected with the same telescope. The molecular clumps include those in giant molecular cloud (GMC) Types I (with no signs of massive star formation), II (with HII regions only), and III (with HII regions and young star clusters). We detected $^{13}$CO($J=3-2$) emission toward all the peaks and found that their intensities are 3 -- 12 times lower than those of $^{12}$CO($J=3-2$). We determined the intensity ratios of $^{12}$CO($J=3-2$) to $^{13}$CO($J=3-2$), $R^{12/13}_{3-2}$, and $^{13}$CO($J=3-2$) to $^{13}$CO($J=1-0$), $R^{13}_{3-2/1-0}$, at 45\arcsec resolution. These ratios were used for radiative transfer calculations in order to estimate temperature and density of the clumps. The parameters of these clumps range kinetic temperature $T\mathrm{_{kin}}$ = 15 -- 200 K, and molecular hydrogen gas density $n(\mathrm{H_2})$ = 8$\times 10^2$ -- 7$\times 10^3$ cm$^{-3}$. We confirmed that the higher density clumps show higher kinetic temperature and that the lower density clumps lower kinetic temperature at a better accuracy than in the previous work. The kinetic temperature and density increase generally from a Type I GMC to a Type III GMC. We interpret that this difference reflects an evolutionary trend of star formation in molecular clumps. The $R^{13}_{3-2/1-0}$ and kinetic temperature of the clumps are well correlated with H$\alpha$ flux, suggesting that the heating of molecular gas $n(\mathrm{H_2})$ = $10^3$ -- $10^4$ cm$^{-3}$ can be explained by stellar FUV photons.Comment: 39 pages, 7 figures, 4 tables. Accepted for publication in The Astronomical Journa

High-mass star formation triggered by collision between CO filaments in N159 West in the Large Magellanic Cloud

We have carried out 13CO(J=2-1) observations of the active star-forming region N159 West in the LMC with ALMA. We have found that the CO distribution at a sub-pc scale is highly elongated with a small width. These elongated clouds called "filaments" show straight or curved distributions with a typical width of 0.5-1.0pc and a length of 5-10pc. All the known infrared YSOs are located toward the filaments. We have found broad CO wings of two molecular outflows toward young high-mass stars in N159W-N and N159W-S, whose dynamical timescale is ~10^4 yrs. This is the first discovery of protostellar outflow in external galaxies. For N159W-S which is located toward an intersection of two filaments we set up a hypothesis that the two filaments collided with each other ~10^5 yrs ago and triggered formation of the high-mass star having ~37 Mo. The colliding clouds show significant enhancement in linewidth in the intersection, suggesting excitation of turbulence in the shocked interface layer between them as is consistent with the magneto-hydro-dynamical numerical simulations (Inoue & Fukui 2013). This turbulence increases the mass accretion rate to ~6x10^-4 Mo yr^-1, which is required to overcome the stellar feedback to form the high-mass star.Comment: 20 pages, 3 figures, accepted for publication in ApJ

The level of urinary semaphorin3A is associated with disease activity in patients with minimal change nephrotic syndrome

Semaphorin3A is a secreted protein known to be involved in organogenesis, immune responses and cancer. In the kidney, semaphorin3A is expressed in the glomerular podocytes, distal tubules and collecting tubules, and believed to play a role in the regulation of the kidney development and function. We examined the serum and urinary semaphorin3A levels in 72 patients with renal disease and 5 healthy volunteers. The patients had been diagnosed with thin basement membrane disease (n=4), minimal change nephrotic syndrome (MCNS; n=22), IgA nephritis (n=21), membranous nephropathy (n=16) and focal segmental glomerular sclerosis (n=9). The level of urinary semaphorin3A in MCNS patients tended to be relatively high among all disease groups. We also investigated the urinary semaphorin3A level in 7 patients with MCNS from disease onset to remission during the drug therapy. MCNS patients in pre-remission states had higher urinary semaphorin3A levels than those in post-remission states receiving immunosuppressive therapies. These results suggested that the urinary semaphorin3A level correlates with the MCNS activity. Semaphorin3A has the potential as a biomarker for MCNS to clarify the reactivity for therapy and may be useful in examining other glomerular diseases with proteinuria as well

Semaphorin3A-Inhibitor Ameliorates Doxorubicin-Induced Podocyte Injury

Podocyte injury is an independent risk factor for the progression of renal diseases. Semaphorin3A (SEMA3A), expressed in podocytes and tubular cells in the mammalian adult kidneys, has been reported to regulate diverse biological functions and be associated with renal diseases. Here, we investigated pathological roles of SEMA3A signaling on podocyte injury using a doxorubicin (Dox)-induced mouse model and examined the therapeutic effect of SEMA3A-inhibitor (SEMA3A-I). We demonstrated that Dox caused massive albuminuria and podocyte apoptosis as well as an increase of SEMA3A expression in podocytes, all of which were ameliorated with SEMA3A-I treatment. In addition, c-Jun N-terminal kinase (JNK), known as a downstream of SEMA3A signaling, was activated in Dox-injected mouse podocytes while SEMA3A-I treatment partially blocked the activation. In vitro, SEMA3A-I protected against Dox-induced podocyte apoptosis and recombinant SEMA3A caused podocyte apoptosis with activation of JNK signaling. JNK inhibitor, SP600125, attenuated SEMA3A-induced podocyte apoptosis, indicating that the JNK pathway would be involved in SEMA3A-induced podocyte apoptosis. Furthermore, the analysis of human data revealed a positive correlation between levels of urinary SEMA3A and protein, suggesting that SEMA3A is associated with podocyte injury. In conclusion, SEMA3A has essential roles in podocyte injury and it would be the therapeutic target for protecting from podocyte injury

An ALMA view of molecular filaments in the Large Magellanic Cloud I: The formation of high-mass stars and pillars in the N159E-Papillon Nebula triggered by a cloud-cloud collision

18 pages, 9 figures, Accepted for publication in ApJInternational audienceWe present the ALMA observations of CO isotopes and 1.3 mm continuum emission toward the N159E-Papillon Nebula in the Large Magellanic Cloud (LMC). The spatial resolution is 0."25-0."28 (0.06-0.07 pc), which is a factor of 3 higher than the previous ALMA observations in this region. The high resolution allowed us to resolve highly filamentary CO distributions with typical width of $\sim$0.1 pc (full width half maximum) and line mass of a few $\times$ 100 $M_{\odot}$ pc$^{-1}$. The filaments (more than ten in number) show outstanding hub-filament structure emanating from the Nebular center toward the north. We identified for the first time two massive protostellar outflows of $\sim$10$^4$ yr dynamical age along one of the most massive filaments. The observations also revealed several pillar-like CO features around the Nebula. The H II region and the pillars show complementary spatial distribution and the column density of the pillars is an order of magnitude higher than that of the pillars in the Eagle nebula (M16) in the Galaxy, suggesting an early stage of pillar formation with an age younger than $\sim$10$^5$ yrs. We suggest that a cloud-cloud collision triggered the formation of the filaments and protostar within the last $\sim$2 Myr. It is possible that the collision is more recent since part of the kpc-scale H I flows come from the tidal interaction resulting from the close encounter between the LMC and SMC $\sim$200 Myr ago as suggested for R136 by Fukui et al. (2017)

An ALMA view of molecular filaments in the Large Magellanic Cloud II: An early stage of high-mass star formation embedded at colliding clouds in N159W-South

Comments: 15 pages, 6 figures; Accepted for publication in ApJInternational audienceWe have conducted ALMA CO isotopes and 1.3 mm continuum observations toward filamentary molecular clouds of the N159W-South region in the Large Magellanic Cloud with an angular resolution of $\sim$0."25 ($\sim$0.07 pc). Although the previous lower resolution ($\sim$1") ALMA observations revealed that there is a high-mass protostellar object at an intersection of two linear-shaped filaments in $^{13}$CO with the length scale of $\sim$10 pc (Fukui et al. 2015), the spatially resolved observations, in particular, toward the highest column density part traced by the 1.3 mm continuum emission, the N159W-South clump, show complicated hub-filamentary structures. We also discovered that there are multiple protostellar sources with bipolar outflows along the massive filament. The redshifted/blueshifted components of the $^{13}$CO emission around the massive filaments/protostars show complementary distributions to each other, which is considered to be a possible piece of evidence for a cloud-cloud collision. We propose a new scenario that the supersonically colliding gas flow triggered the formation of both the massive filament and protostars. This is a modification of the earlier scenario of cloud-cloud collision which postulated the two filamentary clouds prior to the high-mass star formation by Fukui et al. (2015). A recent theoretical study of the shock compression in colliding molecular flows by Inoue et al. (2018) demonstrates that the formation of filaments with hub-structure is a usual outcome of the collision, lending support for the present scenario. In the theory the filaments are formed as dense parts in a shock compressed sheet-like layer, which resembles "an umbrella with pokes"