223 research outputs found
CIB1 protects against MPTP-induced neurotoxicity through inhibiting ASK1.
Calcium and integrin binding protein 1 (CIB1) is a calcium-binding protein that was initially identified as a binding partner of platelet integrin αIIb. Although CIB1 has been shown to interact with multiple proteins, its biological function in the brain remains unclear. Here, we show that CIB1 negatively regulates degeneration of dopaminergic neurons in a mouse model of Parkinson\u27s disease using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Genetic deficiency of the CIB1 gene enhances MPTP-induced neurotoxicity in dopaminergic neurons in CIB1(-/-) mice. Furthermore, RNAi-mediated depletion of CIB1 in primary dopaminergic neurons potentiated 1-methyl-4-phenyl pyrinidium (MPP(+))-induced neuronal death. CIB1 physically associated with apoptosis signal-regulating kinase 1 (ASK1) and thereby inhibited the MPP(+)-induced stimulation of the ASK1-mediated signaling cascade. These findings suggest that CIB1 plays a protective role in MPTP/MPP(+)-induced neurotoxicity by blocking ASK1-mediated signaling
CIB1 protects against MPTP-induced neurotoxicity through inhibiting ASK1
Calcium and integrin binding protein 1 (CIB1) is a calcium-binding protein that was initially identified as a binding partner of platelet integrin αIIb. Although CIB1 has been shown to interact with multiple proteins, its biological function in the brain remains unclear. Here, we show that CIB1 negatively regulates degeneration of dopaminergic neurons in a mouse model of Parkinson's disease using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Genetic deficiency of the CIB1 gene enhances MPTP-induced neurotoxicity in dopaminergic neurons in CIB1-/- mice. Furthermore, RNAi-mediated depletion of CIB1 in primary dopaminergic neurons potentiated 1-methyl-4-phenyl pyrinidium (MPP+)-induced neuronal death. CIB1 physically associated with apoptosis signal-regulating kinase 1 (ASK1) and thereby inhibited the MPP+-induced stimulation of the ASK1-mediated signaling cascade. These findings suggest that CIB1 plays a protective role in MPTP/MPP+-induced neurotoxicity by blocking ASK1-mediated signaling
Efficacy and Safety of Low-Dose Intravesical OnabotulinumtoxinA Injections in Female Patients With Detrusor Overactivity With Detrusor Underactivity
Purpose We assessed the effectiveness and safety of using intravesical onabotulinumtoxinA (onabotA; BOTOX) injection with a low dose (75 units) for treating urinary storage symptoms in patients with detrusor overactivity with detrusor underactivity (DODU) compared to using the standard 100 units of onabotA in patients with overactive bladder (OAB). Methods This ambidirectional study included 121 female patients who received intravesical onabotA injections at our hospitals. A total of 87 patients with OAB and 34 patients with DODU were reviewed using a 3-day voiding diary, uroflowmetry, and questionnaires including the International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score, and Patient Perception of Bladder Condition. Patients were evaluated at baseline, within 2 weeks of treatment, and beyond 3 months after treatment. Results Questionnaire scores of the DODU group demonstrated significant improvement in the short term, with a subsequent decline, but an overall improvement compared to baseline in the long term. Notably, the DODU group exhibited enhanced IPSS voiding scores after the treatment. In the OAB group, most questionnaire scores, excluding the IPSS voiding score, showed significant posttreatment improvement, which was sustained to some extent in the long term. Voiding diary parameters related to storage symptoms were enhanced in both groups. The maximum and mean flow rates decreased in the OAB group but increased in the DODU group, particularly in the short term (P=0.000). The postvoid residual volume increased in both groups after posttreatment, with a mitigated change in the long term. Safety assessments revealed manageable adverse events in both groups with comparable frequencies. Conclusions Low-dose intravesical onabotA for DODU demonstrated a relatively shorter duration of efficacy than OAB. Nonetheless, the treatment improved both storage and voiding symptoms in patients with DODU without significant adverse effects
A Novel Incisionless Disposable Vaginal Device for Female Stress Urinary Incontinence: Efficacy and Quality of Life
Purpose This clinical study sought to evaluate the possible clinical effectiveness and practicality of URINO, an innovative, incisionless, and disposable intravaginal device, designed for patients suffering from stress urinary incontinence. Methods A prospective, multicenter, single-arm clinical trial was carried out, involving women diagnosed with stress urinary incontinence who used a self-inserted, disposable intravaginal pessary device. Comparisons were made between the results of the 20-minute pad-weight gain (PWG) test at baseline and visit 3, where the device was applied. After 1 week of device usage, compliance, satisfaction, the sensation of a foreign body, and adverse events were assessed. Results Out of 45 participants, 39 completed the trial and expressed satisfaction within the modified intention-to-treat group. The average 20-minute PWG of participants was 17.2±33.6 g at baseline and significantly dropped to 5.3±16.2 g at visit 3 with device application. A total of 87.2% of participants exhibited a reduction ratio of PWG by 50% or more, surpassing the clinical trial success benchmark of 76%. The mean compliance was recorded as 76.6%±26.6%, the average visual analogue scale score for patient satisfaction was 6.4±2.6, and the sensation of a foreign body, measured on a 5-point Likert scale, was 3.1±1.2 after 1 week of device use. No serious adverse events were reported; there was 1 instance of microscopic hematuria and 2 cases of pyuria, all of which recovered. Conclusions The investigated device demonstrated significant clinical effectiveness and safety for patients with stress urinary incontinence. It was easy to use, showing favorable patient compliance. We propose that these disposable intravaginal pessaries could potentially be an alternative treatment for patients with stress urinary incontinence who are seeking nonsurgical options or are unable to undergo surgery. Trial Registration The study was registered as a clinical trial (KCT0008369)
KMT-2016-BLG-1107: A New Hollywood-Planet Close/Wide Degeneracy
We show that microlensing event KMT-2016-BLG-1107 displays a new type of
degeneracy between wide-binary and close-binary Hollywood events in which a
giant-star source envelops the planetary caustic. The planetary anomaly takes
the form of a smooth, two-day "bump" far out on the falling wing of the light
curve, which can be interpreted either as the source completely enveloping a
minor-image caustic due to a close companion with mass ratio , or
partially enveloping a major-image caustic due to a wide companion with
. The best estimates of the companion masses are both in the planetary
regime ( and ) but differ by an even larger factor than the mass ratios due to
different inferred host masses. We show that the two solutions can be
distinguished by high-resolution imaging at first light on next-generation
("30m") telescopes. We provide analytic guidance to understand the conditions
under which this new type of degeneracy can appear.Comment: 23 pages, 7 figures, accepted for publication in A
KMT-2018-BLG-1990Lb: A Nearby Jovian Planet From A Low-Cadence Microlensing Field
We report the discovery and characterization of KMT-2018-BLG-1990Lb, a Jovian
planet orbiting a late M dwarf
, at a distance
(D_L=1.23_{-0.43}^{+1.06}\,\kpc), and projected at times the
snow line distance, i.e., a_{\rm snow}\equiv 2.7\,\au (M/M_\odot), This is
the second Jovian planet discovered by KMTNet in its low cadence () fields, demonstrating that this population will be well
characterized based on survey-only microlensing data.Comment: 24 pages, 7 figures, 4 table
KMT-2018-BLG-1292: A Super-Jovian Microlens Planet in the Galactic Plane
We report the discovery of KMT-2018-BLG-1292Lb, a super-Jovian planet orbiting an F or G dwarf , which lies physically within {\cal O}(10\,\pc) of the
Galactic plane. The source star is a heavily extincted luminous
giant that has the lowest Galactic latitude, , of any planetary
microlensing event. The relatively blue blended light is almost certainly
either the host or its binary companion, with the first explanation being
substantially more likely. This blend dominates the light at band and
completely dominates at and bands. Hence, the lens system can be probed
by follow-up observations immediately, i.e., long before the lens system and
the source separate due to their relative proper motion. The system is well
characterized despite the low cadence -- of
observations and short viewing windows near the end of the bulge season. This
suggests that optical microlensing planet searches can be extended to the
Galactic plane at relatively modest cost.Comment: 35 pages, 3 Tables, 8 figure
OGLE-2018-BLG-0532Lb: Cold Neptune With Possible Jovian Sibling
We report the discovery of the planet OGLE-2018-BLG-0532Lb, with very obvious
signatures in the light curve that lead to an estimate of the planet-host mass
ratio . Although there are
no obvious systematic residuals to this double-lens/single-source (2L1S) fit,
we find that can be significantly improved by adding either a third
lens (3L1S, ) or second source (2L2S, ) to
the lens-source geometry. After thorough investigation, we conclude that we
cannot decisively distinguish between these two scenarios and therefore focus
on the robustly-detected planet. However, given the possible presence of a
second planet, we investigate to what degree and with what probability such
additional planets may affect seemingly single-planet light curves. Our best
estimates for the properties of the lens star and the secure planet are: a host
mass , system distance kpc and planet mass
with projected separation au.
However, there is a relatively bright (and also relatively blue) star
projected within mas of the lens, and if future high-resolution images
show that this is coincident with the lens, then it is possible that it is the
lens, in which case, the lens would be both more massive and more distant than
the best-estimated values above.Comment: 48 pages, 9 figures, 7 table
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