Progression of Parkinson's Disease Pathology Is Reproduced by Intragastric Administration of Rotenone in Mice

In patients with Parkinson''s disease (PD), the associated pathology follows a characteristic pattern involving inter alia the enteric nervous system (ENS), the dorsal motor nucleus of the vagus (DMV), the intermediolateral nucleus of the spinal cord and the substantia nigra, providing the basis for the neuropathological staging of the disease. Here we report that intragastrically administered rotenone, a commonly used pesticide that inhibits Complex I of the mitochondrial respiratory chain, is able to reproduce PD pathological staging as found in patients. Our results show that low doses of chronically and intragastrically administered rotenone induce alpha-synuclein accumulation in all the above-mentioned nervous system structures of wild-type mice. Moreover, we also observed inflammation and alpha-synuclein phosphorylation in the ENS and DMV. HPLC analysis showed no rotenone levels in the systemic blood or the central nervous system (detection limit [rotenone]<20 nM) and mitochondrial Complex I measurements showed no systemic Complex I inhibition after 1.5 months of treatment. These alterations are sequential, appearing only in synaptically connected nervous structures, treatment time-dependent and accompanied by inflammatory signs and motor dysfunctions. These results strongly suggest that the local effect of pesticides on the ENS might be sufficient to induce PD-like progression and to reproduce the neuroanatomical and neurochemical features of PD staging. It provides new insight into how environmental factors could trigger PD and suggests a transsynaptic mechanism by which PD might spread throughout the central nervous system.     

DHP-Derivative and Low Oxygen Tension Effectively Induces Human Adipose Stromal Cell Reprogramming

Background and Methods

In this study, we utilized a combination of low oxygen tension and a novel anti-oxidant, 4-(3,4-dihydroxy-phenyl)-derivative (DHP-d) to directly induce adipose tissue stromal cells (ATSC) to de-differentiate into more primitive stem cells. De-differentiated ATSCs was overexpress stemness genes, Rex-1, Oct-4, Sox-2, and Nanog. Additionally, demethylation of the regulatory regions of Rex-1, stemnesses, and HIF1α and scavenging of reactive oxygen species were finally resulted in an improved stem cell behavior of de-differentiate ATSC (de-ATSC). Proliferation activity of ATSCs after dedifferentiation was induced by REX1, Oct4, and JAK/STAT3 directly or indirectly. De-ATSCs showed increased migration activity that mediated by P38/JUNK and ERK phosphorylation. Moreover, regenerative efficacy of de-ATSC engrafted spinal cord-injured rats and chemical-induced diabetes animals were significantly restored their functions.

Conclusions/Significance

Our stem cell remodeling system may provide a good model which would provide insight into the molecular mechanisms underlying ATSC proliferation and transdifferentiation. Also, these multipotent stem cells can be harvested may provide us with a valuable reservoir of primitive and autologous stem cells for use in a broad spectrum of regenerative cell-based disease therapy.     

Plants,microorganisms, and soil temperatures contribute to a decrease in methane fluxes on a drained Arctic floodplain

As surface temperatures are expected to rise in the future, ice‐rich permafrost may thaw, altering soil topography and hydrology and creating a mosaic of wet and dry soil surfaces in the Arctic. Arctic wetlands are large sources of CH₄, and investigating effects of soil hydrology on CH₄ fluxes is of great importance for predicting ecosystem feedback in response to climate change. In this study, we investigate how a decade‐long drying manipulation on an Arctic floodplain influences CH₄‐associated microorganisms, soil thermal regimes, and plant communities. Moreover, we examine how these drainage‐induced changes may then modify CH₄ fluxes in the growing and nongrowing seasons. This study shows that drainage substantially lowered the abundance of methanogens along with methanotrophic bacteria, which may have reduced CH₄ cycling. Soil temperatures of the drained areas were lower in deep, anoxic soil layers (below 30 cm), but higher in oxic topsoil layers (0–15 cm) compared to the control wet areas. This pattern of soil temperatures may have reduced the rates of methanogenesis while elevating those of CH₄ oxidation, thereby decreasing net CH₄ fluxes. The abundance of Eriophorum angustifolium, an aerenchymatous plant species, diminished significantly in the drained areas. Due to this decrease, a higher fraction of CH₄ was alternatively emitted to the atmosphere by diffusion, possibly increasing the potential for CH₄ oxidation and leading to a decrease in net CH₄ fluxes compared to a control site. Drainage lowered CH₄ fluxes by a factor of 20 during the growing season, with postdrainage changes in microbial communities, soil temperatures, and plant communities also contributing to this reduction. In contrast, we observed CH₄ emissions increased by 10% in the drained areas during the nongrowing season, although this difference was insignificant given the small magnitudes of fluxes. This study showed that long‐term drainage considerably reduced CH₄ fluxes through modified ecosystem properties.     

Efficiency Enhancement of Organic Solar Cells Using Hydrophobic Antireflective Inverted Moth‐Eye Nanopatterned PDMS Films

Poly‐dimethylsiloxane (PDMS) films with 2D periodic inverted moth‐eye nanopatterns on one surface are implemented as antireflection (AR) layers on a glass substrate for efficient light capture in encapsulated organic solar cells (OSCs). The inverted moth‐eye nanopatterned PDMS (IMN PDMS) films are fabricated by a soft imprint lithographic method using conical subwavelength grating patterns formed by laser interference lithography/dry etching. Their optical characteristics, together with theoretical analysis using rigorous coupled‐wave analysis simulation, and wetting behaviors are investigated. For a period of 380 nm, IMN PDMS films laminated on glass substrates exhibit a hydrophobic surface with a water contact angle (θ_CA) of ≈120° and solar weighted transmittance (SWT) of ≈94.2%, both significantly higher than those (θ_CA≈ 36° and SWT ≈ 90.3%) of bare glass substrates. By employing IMN PDMS films with a period of 380 nm on glass substrates for OSCs, an enhanced power conversion efficiency (PCE) of 6.19% is obtained mainly due to the increased short‐circuit current density (J_sc) of 19.74 mA cm^‐2 compared to the OSCs with the bare glass substrates (PCE = 5.16% and J_sc = 17.25 mA cm^‐2). For the OSCs, the device stability is also studied.     

The Long-Term Influence of Body Mass Index on the Success Rate of Mid-Urethral Sling Surgery among Women with Stress Urinary Incontinence or Stress-Predominant Mixed Incontinence: Comparisons between Retropubic and Transobturator Approaches

Objectives

Mid-urethral sling (MUS) surgery for the treatment of urinary incontinence has been widespread since the introduction of tension-free vaginal tape in the mid-1990s. The majority of studies with short-term follow-up <2 years found no differences in the surgical outcomes according to body mass index (BMI). However, considering the chronic influence of obesity on pelvic floor musculature, it is cautiously speculated that higher BMI could increase stress on pelvic floor and sub-urethral tape, possibly decreasing the long-term success rate in the obese population. We aimed to compare the long-term effects of BMI on the outcomes of MUS between women with retropubic and transobturator approaches.

Methods

We performed a retrospective analysis on 243 consecutive women who received MUS and were followed up for ≥36 months. The influence of BMI on the success rates was separately estimated and the factors for treatment failure were examined using logistic regression in either approach.

Results

The mean follow-up was 58.4 months, and 30.5% were normal weight, 51.0% overweight, and 18.5% obese. Patients received either the retropubic (30.5%) or transobturator (69.5%) approach. The success rates (%) under the transobturator approach differed according to the BMI groups (94.3, 88.6, and 78.6, respectively; P = 0.037) while those under the retropubic approach were not different according to the BMI groups. However, in multivariate models, only the presence of preoperative mixed urinary incontinence (MUI) was proven to be the risk factor for treatment failure in the transobturator approach (OR 6.39, P = 0.003). The percent of subjects with MUI was higher in obese women than in non-obese women with the transobturator approach.

Conclusions

BMI was not independently associated with failures in either approach. Higher success rates in women with lower BMI in the transobturator approach were attributed to the lower percent of preoperative MUI in those with lower BMI.     

Tonsil-derived mesenchymal stem cells alleviate concanavalin A-induced acute liver injury

Acute liver failure, the fatal deterioration of liver function, is the most common indication for emergency liver transplantation, and drug-induced liver injury and viral hepatitis are frequent in young adults. Stem cell therapy has come into the limelight as a potential therapeutic approach for various diseases, including liver failure and cirrhosis. In this study, we investigated therapeutic effects of tonsil-derived mesenchymal stem cells (T-MSCs) in concanavalin A (ConA)- and acetaminophen-induced acute liver injury. ConA-induced hepatitis resembles viral and immune-mediated hepatic injury, and acetaminophen overdose is the most frequent cause of acute liver failure in the United States and Europe. Intravenous administration of T-MSCs significantly reduced ConA-induced hepatic toxicity, but not acetaminophen-induced liver injury, affirming the immunoregulatory capacity of T-MSCs. T-MSCs were successfully recruited to damaged liver and suppressed inflammatory cytokine secretion. T-MSCs expressed high levels of galectin-1 and -3, and galectin-1 knockdown which partially diminished interleukin-2 and tumor necrosis factor α secretion from cultured T-cells. Galectin-1 knockdown in T-MSCs also reversed the protective effect of T-MSCs on ConA-induced hepatitis. These results suggest that galectin-1 plays an important role in immunoregulation of T-MSCs, which contributes to their protective effect in immune-mediated hepatitis. Further, suppression of T-cell activation by frozen and thawed T-MSCs implies great potential of T-MSC banking for clinical utilization in immune-mediated disease.     

Regulation of c-Myc Expression by Ahnak Promotes Induced Pluripotent Stem Cell Generation

We have previously reported that Ahnak-mediated TGFβ signaling leads to down-regulation of c-Myc expression. Here, we show that inhibition of Ahnak can promote generation of induced pluripotent stem cells (iPSC) via up-regulation of endogenous c-Myc. Consistent with the c-Myc inhibitory role of Ahnak, mouse embryonic fibroblasts from Ahnak-deficient mouse (Ahnak^−/− MEF) show an increased level of c-Myc expression compared with wild type MEF. Generation of iPSC with just three of the four Yamanaka factors, Oct4, Sox2, and Klf4 (hereafter 3F), was significantly enhanced in Ahnak^−/− MEF. Similar results were obtained when Ahnak-specific shRNA was applied to wild type MEF. Of note, expressionof Ahnak was significantly induced during the formation of embryoid bodies from embryonic stem cells, suggesting that Ahnak-mediated c-Myc inhibition is involved in embryoid body formation and the initial differentiation of pluripotent stem cells. The iPSC from 3F-infected Ahnak^−/− MEF cells (Ahnak^−/−-iPSC-3F) showed expression of all stem cell markers examined and the capability to form three primary germ layers. Moreover, injection of Ahnak^−/−-iPSC-3F into athymic nude mice led to development of teratoma containing tissues from all three primary germ layers, indicating that iPSC from Ahnak^−/− MEF are bona fide pluripotent stem cells. Taken together, these data provide evidence for a new role for Ahnak in cell fate determination during development and suggest that manipulation of Ahnak and the associated signaling pathway may provide a means to regulate iPSC generation.     

Aerial dispersal of phytoseiid mites (Acari: Phytoseiidae): estimating falling speed and dispersal distance of adult females

Aerial dispersal is important to immigration and redistribution of phytoseiid mites that often can provide biological control of spider mite pests. Falling speed of a mite and wind largely determine dispersal distance of such a passively blown organism. A diffusion model of wind-blown phytoseiids could provide insight into their dispersal. To this end, we measured body weights and falling speeds of adult females of 13 phytoseiid and one tetranychid mite species. These data were then incorporated into seed dispersal models (Greene and Johnson, Okubo and Levin) and results were compared to mite dispersal distances in wind tunnel, greenhouse and field. Weights of phytoseiid species ranged from 5.25 to 2l.7 μg; starved mites weighed less than fed mites. Geometric diameters ( d _g ) of idiosomas were correlated to weights. Falling speeds for phytoseiids were 0.39–0.73 m/s, and less than for T. urticae (0.79 m/s) in still air. In some species, active mites had slower falling speeds than inactive (anesthetized) mites indicating that behavior may influence falling. Starved mites had significantly slower falling speeds than fed mites and dispersed farther. Equation-based estimates of falling speed were close to measured ones (2–8% deviation) for some species. There were significant relationships between falling speed and body weight and morphological traits. Greene and Johnson's seed dispersal model provided better fits to dispersal of mites in the wind tunnel, greenhouse and field studies than Okubo and Levin's model. Limits of models in describing mite dispersal distance and applications to IPM are discussed.