The high optical brightness of the BlueWalker 3 satellite.

Large constellations of bright artificial satellites in low Earth orbit pose significant challenges to ground-based astronomy1. Current orbiting constellation satellites have brightnesses between apparent magnitudes 4 and 6, whereas in the near-infrared Ks band, they can reach magnitude 2 (ref. 2). Satellite operators, astronomers and other users of the night sky are working on brightness mitigation strategies3,4. Radio emissions induce further potential risk to ground-based radio telescopes that also need to be evaluated. Here we report the outcome of an international optical observation campaign of a prototype constellation satellite, AST SpaceMobile's BlueWalker 3. BlueWalker 3 features a 64.3 m2 phased-array antenna as well as a launch vehicle adaptor (LVA)5. The peak brightness of the satellite reached an apparent magnitude of 0.4. This made the new satellite one of the brightest objects in the night sky. Additionally, the LVA reached an apparent V-band magnitude of 5.5, four times brighter than the current International Astronomical Union recommendation of magnitude 7 (refs. 3,6); it jettisoned on 10 November 2022 (Universal Time), and its orbital ephemeris was not publicly released until 4 days later. The expected build-out of constellations with hundreds of thousands of new bright objects1 will make active satellite tracking and avoidance strategies a necessity for ground-based telescopes.

Circadian rhythm disruptions associated with opioid use disorder in synaptic proteomes of human dorsolateral prefrontal cortex and nucleus accumbens.

Opioid craving and relapse vulnerability is associated with severe and persistent sleep and circadian rhythm disruptions. Understanding the neurobiological underpinnings of circadian rhythms and opioid use disorder (OUD) may prove valuable for developing new treatments for opioid addiction. Previous work indicated molecular rhythm disruptions in the human brain associated with OUD, highlighting synaptic alterations in the dorsolateral prefrontal cortex (DLPFC) and nucleus accumbens (NAc)-key brain regions involved in cognition and reward, and heavily implicated in the pathophysiology of OUD. To provide further insights into the synaptic alterations in OUD, we used mass-spectrometry based proteomics to deeply profile protein expression alterations in bulk tissue and synaptosome preparations from DLPFC and NAc of unaffected and OUD subjects. We identified 55 differentially expressed (DE) proteins in DLPFC homogenates, and 44 DE proteins in NAc homogenates, between unaffected and OUD subjects. In synaptosomes, we identified 161 and 56 DE proteins in DLPFC and NAc, respectively, of OUD subjects. By comparing homogenate and synaptosome protein expression, we identified proteins enriched specifically in synapses that were significantly altered in both DLPFC and NAc of OUD subjects. Across brain regions, synaptic protein alterations in OUD subjects were primarily identified in glutamate, GABA, and circadian rhythm signaling. Using time-of-death (TOD) analyses, where the TOD of each subject is used as a time-point across a 24-h cycle, we were able to map circadian-related changes associated with OUD in synaptic proteomes associated with vesicle-mediated transport and membrane trafficking in the NAc and platelet-derived growth factor receptor beta signaling in DLPFC. Collectively, our findings lend further support for molecular rhythm disruptions in synaptic signaling in the human brain as a key factor in opioid addiction.

12-h clock regulation of genetic information flow by XBP1s.

Our group recently characterized a cell-autonomous mammalian 12-h clock independent from the circadian clock, but its function and mechanism of regulation remain poorly understood. Here, we show that in mouse liver, transcriptional regulation significantly contributes to the establishment of 12-h rhythms of mRNA expression in a manner dependent on Spliced Form of X-box Binding Protein 1 (XBP1s). Mechanistically, the motif stringency of XBP1s promoter binding sites dictates XBP1s's ability to drive 12-h rhythms of nascent mRNA transcription at dawn and dusk, which are enriched for basal transcription regulation, mRNA processing and export, ribosome biogenesis, translation initiation, and protein processing/sorting in the Endoplasmic Reticulum (ER)-Golgi in a temporal order consistent with the progressive molecular processing sequence described by the central dogma information flow (CEDIF). We further identified GA-binding proteins (GABPs) as putative novel transcriptional regulators driving 12-h rhythms of gene expression with more diverse phases. These 12-h rhythms of gene expression are cell autonomous and evolutionarily conserved in marine animals possessing a circatidal clock. Our results demonstrate an evolutionarily conserved, intricate network of transcriptional control of the mammalian 12-h clock that mediates diverse biological pathways. We speculate that the 12-h clock is coopted to accommodate elevated gene expression and processing in mammals at the two rush hours, with the particular genes processed at each rush hour regulated by the circadian and/or tissue-specific pathways.

Anti-Inflammatory Activity of 1,6,7-Trihydroxy-2-(1,1-dimethyl-2-propenyl)-3-methoxyxanthone Isolated from Cudrania tricuspidata via NF-κB, MAPK, and HO-1 Signaling Pathways in Lipopolysaccharide-Stimulated RAW 264.7 and BV2 Cells.

Neuroinflammation activated by microglia affects inflammatory pain development. This study aimed to explore the anti-inflammatory properties and mechanisms of 1,6,7-trihydroxy-2-(1,1-dimethyl-2-propenyl)-3-methoxyxanthone (THMX) from Cudrania tricuspidata in microglia activation-mediated inflammatory pain. In RAW 264.7 and BV2 cells, THMX has been shown to reduce lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and pro-inflammatory mediators and cytokines, including nitric oxide (NO), prostaglandin (PG) E2, interleukin (IL)-6, and tumor necrosis factor alpha (TNF-α). THMX also decreased LPS-induced phosphorylation of mitogen-activated protein kinase (MAPK) and the activation of p65 nuclear factor kappa B (NF-κB). Interestingly, THMX also activated heme oxygenase (HO)-1 expression. These findings suggest that THMX is a promising biologically active compound against inflammation through preventing MAPKs and NF-ĸB and activating HO-1 signaling pathways.

Macluraxanthone B inhibits LPS-induced inflammatory responses in RAW264.7 and BV2 cells by regulating the NF-κB and MAPK signaling pathways.

OBJECTIVE: The prenylated xanthones compounds, macluraxanthone B (MCXB) was isolated from the MeOH extracts of Cudrania tricuspidata. In this study, we investigated the effect of MCXB on inflammatory response. MATERIALS AND METHODS: Anti-inflammatory effects of MCXB were examined in lipopolysaccharide (LPS)-stimulated RAW264.7 and BV2 cells. We observed their anti-inflammatory effects by ELISA, western blot analysis, and immunofluorescence. RESULTS: MCXB significantly inhibited the LPS-stimulated production of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-6 (IL-6), and tumor necrosis factor (TNF)-α in RAW264.7 and BV2 cells. MCXB also reduced the LPS-induced expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 proteins. Incubating cells with MCXB prevented subsequent activation of the nuclear factor kappa B (NF-κB) signaling pathway by inhibiting the nuclear localization and DNA-binding activity of the p65 subunit induced by LPS. MCXB inhibited the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 mitogen-activated protein kinases (MAPKs) in RAW264.7 and BV2 cells. MCXB induced the expression of heme oxygenase (HO)-1 protein, and the inhibitory effect of MCXB on nitric oxide production was partially reversed by a selective HO-1 inhibitor. DISCUSSION AND CONCLUSIONS: Our results suggested that the anti-inflammatory effect of MCXB is partly regulated by HO-1 induction. In conclusion, MCXB could be a useful candidate for the development of therapeutic and preventive agents to treat inflammatory diseases.

Role of Seed Layer Crystalline Quality in Photoresponse Performance of Hydrothermally Grown ZnO Nanorods.

We investigated the effects of the crystalline state for seed layers (SLs) on the growth morphology and material characteristics for hydrothermally grown ZnO nanorods (NRs). For this, preheating (PH) at different temperatures (100-300 °C) and O2 plasma treatment (PT) for 9 min were performed during the growth of SLs on p-Si by the aqueous solution-based method to provide the characteristic change on the NR growth platform. An improvement in material properties was achieved from the ZnO NRs grown on the SL crystals of enhanced crystalline quality in terms of the increased preferred orientation (002), the higher UV emission with suppressed deep-level emissions, the recovery of O/Zn stoichiometry, and the reduction of various intrinsic defects. Ultraviolet photodiodes of a p-Si/n-ZnO-NR structure fabricated under the SL conditions of O2 PT and PH at 100 °C showed a significantly enhanced on-off current ratio of ~90 at +5 V and faster photoresponse characteristics presenting a reduction in the fall time from 16 to 9 s.

HDAC5--a critical player in the p53 acetylation network.

In this issue of Molecular Cell, Sen et al. (2013) identify HDAC5 as a deacetylase with specificity for the K120 site of p53, a key residue of p53 that undergoes acetylation after DNA damage and regulates target gene selection.

Meta-analysis of effects of inoculation with Lactobacillus buchneri, with or without other bacteria, on silage fermentation, aerobic stability, and performance of dairy cows.

A meta-analysis of 158 peer-reviewed articles was conducted to examine effects of inoculation with Lactobacillus buchneri (LB)-based inoculants (LBB) that did or did not include homolactic or obligate heterolactic bacteria on silage fermentation and aerobic stability. A complementary meta-analysis of 12 articles examined LBB inoculation effects on dairy cow performance. Raw mean differences between inoculant and control treatment means weighted by inverse variance were compared with a hierarchical effects model that included robust variance estimation. Meta-regression and subgrouping analysis were used to identify effects of covariates including forage type, application rate (≤104, 105, 106, or ≥ 107 cfu/g as fed), bacteria type (LB vs. LB plus other bacteria), enzyme inclusion, ensiling duration, and silo type (laboratory or farm scale). Inoculation with LBB increased acetate (62%), 1, 2 propanediol (364%) and propionate (30%) concentration and aerobic stability (73.8%) and reduced lactate concentration (7.2%), yeast counts (7-fold) and mold counts (3-fold). Feeding inoculated silage did not affect milk yield, dry matter intake, and feed efficiency in lactating dairy cows. However, forage type, inoculant composition, and dose effects on silage quality measures were evident. Inoculation with LBB increased aerobic stability of all silages except tropical grasses. Adding obligate homolactic or facultative heterolactic bacteria to LB prevented the small increase in DM losses caused by LB alone. The 105 and 106 cfu/g rates were most effective at minimizing DM losses while aerobic stability was only increased with 105, 106, and ≥ 107 cfu/g rates. Inoculation with LBB increased acetate concentration, reduced yeast counts and improved aerobic stability but did not improve dairy cow performance.

Enhancement in the photonic response of ZnO nanorod-gated AlGaN/GaN HEMTs with N2O plasma treatment.

We demonstrate an improvement in the photoresponse characteristics of ultraviolet (UV) photodetectors (PDs) using the N2O plasma-treated ZnO nanorod (NR) gated AlGaN/GaN high electron mobility transistor (HEMT) structure. The PDs fabricated with ZnO NRs plasma-treated for 6 min show superior performance in terms of responsivity (∼1.54×10 5 A/W), specific detectivity (∼ 4.7×1013 cm·Hz-1/2/W), and on/off current ratio (∼40). These improved performance parameters are the best among those from HEMT-based PDs reported to date. Photoluminescence analysis shows a significant enhancement in near band edge emission due to the effective suppression of native defects near the surface of ZnO NRs after plasma treatment. As our X-ray photoelectron spectroscopy reveals a very high O/Zn ratio of ∼0.96 from the NR samples plasma-treated for 6 min, the N2O plasma radicals also show a clear impact on ZnO stoichiometry. From our X-ray diffraction analysis, the plasma-treated ZnO NRs show much greater improvement in (002) peak intensity and degree of (002) orientation (∼0.996) than those of as-grown NRs. This significant enhancement in (002) degree of orientation and stoichiometry in ZnO nano-crystals contribute to the enhancement in photoresponse characteristics of the PDs.

Effects of wild or mutated inoculants on rye silage and its rumen fermentation indices.

OBJECTIVE: This study was conducted to confirm the effects of new inoculants producing-antifungal or esterase substances on rye silage and its rumen fermentation indices by comparing wild with mutated types. METHODS: Rye harvested at dough stage was ensiled into 3 L mini bucket silo (1 kg) for 90 d in triplicate following: distilled water at 20 µL/g (CON); Lactobacillus brevis 100D8 (AT) and its inactivation of antifungal genes (AT-m) at 1.2×105 cfu/g, respectively; and Leuconostoc holzapfelii 5H4 (FD) and its inactivation of esterase genes (FD-est) at 1.0×105 cfu/g, respectively. After silo opened, silage was sub-sampled for the analysis of ensiling quality and its rumen fermentation indices. RESULTS: Among the wild type inoculants (CON vs AT vs FD), FD inoculant had higher (p<0.05) in vitro digestibilities of dry matter and neutral detergent fiber, the total degradable fraction, and total volatile fatty acid in rumen, while AT inoculant had higher (p<0.05) lactate, acetate, and lactic acid bacteria in silage. Silage pH and the potentially degradable fraction in rumen increased (p<0.05) by inactivation of antifungal activity (AT vs AT-m), but lactate, acetate, and lactic acid bacteria of silage decreased (p<0.05). In silage, acetate increased (p<0.05) by inactivation of esterase activity (FD vs FD-est) with decreases (p<0.05) of pH, ammonia-N, lactate, and yeast. Moreover, inactivation of esterase activity clearly decreased (p<0.05) in vitro digestibilities of dry matter and neutral detergent fiber, the total degradable fraction, and total volatile fatty acid in the rumen. CONCLUSION: This study concluded that FD inoculant confirmed esterase activity on rye silage harvested at dough stage, while AT inoculant could not be confirmed with antifungal activity due to the absence of mold in all silages.

Correction to: inhibition of p38 MAPK activity leads to cell type-specific effects on the molecular circadian clock and time-dependent reduction of glioma cell invasiveness.

Following publication of the original article [1], we have been notified that the tagging of one of the author names was done incorrectly in the XML version of the paper. The online and pdf versions of this paper are not affected by the change. Original and corrected tagging can be seen below. The original article has been corrected.

Shift work cycle-induced alterations of circadian rhythms potentiate the effects of high-fat diet on inflammation and metabolism.

Based on genetic models with mutation or deletion of core clock genes, circadian disruption has been implicated in the pathophysiology of metabolic disorders. Thus, we examined whether circadian desynchronization in response to shift work-type schedules is sufficient to compromise metabolic homeostasis and whether inflammatory mediators provide a key link in the mechanism by which alterations of circadian timekeeping contribute to diet-induced metabolic dysregulation. In high-fat diet (HFD)-fed mice, exposure to chronic shifts of the light-dark cycle (12 h advance every 5 d): 1) disrupts photoentrainment of circadian behavior and modulates the period of spleen and macrophage clock gene rhythms; 2) potentiates HFD-induced adipose tissue infiltration and activation of proinflammatory M1 macrophages; 3) amplifies macrophage proinflammatory cytokine expression in adipose tissue and bone marrow-derived macrophages; and 4) exacerbates diet-induced increases in body weight, insulin resistance, and glucose intolerance in the absence of changes in total daily food intake. Thus, complete disruption of circadian rhythmicity or clock gene function as transcription factors is not requisite to the link between circadian and metabolic phenotypes. These findings suggest that macrophage proinflammatory activation and inflammatory signaling are key processes in the physiologic cascade by which dysregulation of circadian rhythmicity exacerbates diet-induced systemic insulin resistance and glucose intolerance.-Kim, S.-M., Neuendorff, N., Alaniz, R. C., Sun, Y., Chapkin, R. S., Earnest, D. J. Shift work cycle-induced alterations of circadian rhythms potentiate the effects of high-fat diet on inflammation and metabolism.

Sea Squirt (Halocynthia roretzi) Hydrolysates Induce Apoptosis in Human Colon Cancer HT-29 Cells through Activation of Reactive Oxygen Species.

Recent evidence provides that seafood has a lot of health benefits due to its unique bioactive compounds. Sea squirt is widely cultured and consumed as a foodstuff in Korea; however, seldom reports with reference to bioactivities are available until now. In this study, edible part of sea squirt was hydrolyzed by pepsin and its hydrolysates was evaluated for anticancer effect on human colon cancer HT-29 cells. Sea squirt hydrolysates (SSQ) reduced HT-29 cell viability. Treatment with SSQ resulted in the increase in reactive oxygen species (ROS) generation followed by disruption of mitochondrial membrane potential (MMP). Flow cytometry analysis revealed that SSQ induced G2/M phase arrest and apoptosis evidenced by Hoechst 33342 staining. Levels of mRNA expression by real-time polymerase chain reaction (PCR) showed that treatment with SSQ in HT-29 cells upregulated expression of p53, bax, and caspase-3 genes and downregulated expression of bcl-2 gene. Protein level of cytochrome c into cytosol and caspase-3 by Western blotting were also increased by treatment with SSQ in HT-29 cells. These results suggest that SSQ may be useful for functional food ingredients and/or nutraceuticals.

Temperature and microbial changes of corn silage during aerobic exposure.

OBJECTIVE: This study was conducted to estimate the temperature and microbial changes of corn silages during aerobic exposure. METHODS: Kwangpyeongok (KW) and Pioneer 1543 (PI) corn hybrids were harvested at 29.7% of dry matter and chopped to 3 to 5 cm lengths. Homo (Lactobacillus plantarum; LP) or hetero (Lactobacillus buchneri; LB) fermentative inoculants at 1.2×105 colony forming unit/g of fresh forage was applied to the chopped corn forage which was then ensiled in quadruplicate with a 2×2 (hybrid×inoculant) treatment arrangement for 100 days. After the silo was opened, silage was sub-sampled for analysis of chemical compositions, in vitro digestibility, and fermentation indices. The fresh silage was continued to determine aerobic exposure qualities by recorded temperature and microbial changes. RESULTS: The KW silages had higher (p<0.01) in vitro digestibilities of dry matter and neutral detergent fiber than those of PI silages. Silages applied with LB had higher (p<0.001) acetate concentration, but lower (p<0.01) lactate concentration and lactate to acetate ratio than those of LP silages. The interaction effect among hybrid and inoculant was detected in acetate production (p = 0.008), aerobic stability (p = 0.006), and lactic acid bacteria count (p = 0.048). The yeast was lower (p = 0.018) in LB silages than that in LP silages. During the aerobic exposure, PI silages showed higher (p<0.05) temperature and mold than KW silages, while LP silages had higher (p<0.05) lactic acid bacteria and yeast than LB silages. CONCLUSION: The results indicated that the changes of silage temperature during aerobic exposure seems mainly affected by mold growth, while applied LB only enhanced aerobic stability of PI silages.

Inhibition of p38 MAPK activity leads to cell type-specific effects on the molecular circadian clock and time-dependent reduction of glioma cell invasiveness.

BACKGROUND: The circadian clock is the basis for biological time keeping in eukaryotic organisms. The clock mechanism relies on biochemical signaling pathways to detect environmental stimuli and to regulate the expression of clock-controlled genes throughout the body. MAPK signaling pathways function in both circadian input and output pathways in mammals depending on the tissue; however, little is known about the role of p38 MAPK, an established tumor suppressor, in the mammalian circadian system. Increased expression and activity of p38 MAPK is correlated with poor prognosis in cancer, including glioblastoma multiforme; however, the toxicity of p38 MAPK inhibitors limits their clinical use. Here, we test if timed application of the specific p38 MAPK inhibitor VX-745 reduces glioma cell invasive properties in vitro. METHODS: The levels and rhythmic accumulation of active phosphorylated p38 MAPK in different cell lines were determined by western blots. Rhythmic luciferase activity from clock gene luciferase reporter cells lines was used to test the effect of p38 MAPK inhibition on clock properties as determined using the damped sine fit and Levenberg-Marquardt algorithm. Nonlinear regression and Akaike's information criteria were used to establish rhythmicity. Boyden chamber assays were used to measure glioma cell invasiveness following time-of-day-specific treatment with VX-745. Significant differences were established using t-tests. RESULTS: We demonstrate the activity of p38 MAPK cycles under control of the clock in mouse fibroblast and SCN cell lines. The levels of phosphorylated p38 MAPK were significantly reduced in clock-deficient cells, indicating that the circadian clock plays an important role in activation of this pathway. Inhibition of p38 MAPK activity with VX-745 led to cell-type-specific period changes in the molecular clock. In addition, phosphorylated p38 MAPK levels were rhythmic in HA glial cells, and high and arrhythmic in invasive IM3 glioma cells. We show that inhibition of p38 MAPK activity in IM3 cells at the time of day when the levels are normally low in HA cells under control of the circadian clock, significantly reduced IM3 invasiveness. CONCLUSIONS: Glioma treatment with p38 MAPK inhibitors may be more effective and less toxic if administered at the appropriate time of the day.

GSK-3ß-mediated regulation of cadmium-induced cell death and survival.

BACKGROUND: Previous studies indicated that cadmium (Cd) increases PI3-kinase/Akt phosphorylation, resulting in an alteration in GSK-3ß activity. However, the mechanism of Cd-induced endoplasmic reticulum (ER) stress in neuronal cells has yet to be studied in needs further elucidation. We examined the role of GSK-3ß in Cd-induced neuronal cell death and the related downstream signaling pathways. METHODS: SH-SY5Y human neuroblastoma cells were treated with 10 or 20 µM BAPTA-AM and 1 µM wortmannin for 30 min and then incubated with 25 µM Cd for 12 h. Apoptotic cells were visualized via DAPI and PI staining. Data were evaluated with one-way analysis of variance (ANOVA) followed by Student's t-test. Data are expressed as the means ± SD of experiments performed at least three times. RESULTS: Treatment of human neuronal SH-SY5Y cells with Cd induced ER, stress as evidenced by the increased expression of GRP78, which is a marker of ER stress. Cd exposure significantly increased the phosphorylation of Akt at thr308 and ser473 and that of GSK-3ß at ser9 in a time-dependent manner, while the total protein levels of GSK-3ß and Akt did not change. Cd-induced apoptosis was higher in GSK-3ß-knockdown cells than in normal cells. CONCLUSIONS: Our data suggest that Akt/GSK-3ß signaling activated by Cd is involved in neuronal cell survival.

Feasibility of improved motion-sensitized driven-equilibrium (iMSDE) prepared 3D T1-weighted imaging in the diagnosis of vertebrobasilar artery dissection.

BACKGROUND AND PURPOSE: This study was to evaluate the diagnostic value of improved motion-sensitized driven-equilibrium (iMSDE)-prepared 3D T1-weighted magnetic resonance imaging (MRI) (iMSDE-3DMRI) in intracranial vertebrobasilary dissection (VBD) and to compare iMSDE-3DMRI images with those obtained using 2D high-resolution (HR) MRI with respect to their diagnostic performance in VBD. MATERIALS AND METHODS: We retrospectively reviewed 105 lesions from 102 patients who underwent multimodal imaging and contrast-enhanced iMSDE-3DMRI (CE-iMSDE-3DMRI). The 2D-HRMRI protocol comprised four axial HR images. The CE-iMSDE-3DMRI images were reformatted in the axial, coronal, and sagittal planes. The 2D-HRMRI-based diagnosis was compared with the final diagnosis. The 2D-HRMRI and CE-iMSDE-3DMRI images were examined independently for the diagnosis performance of dissection. RESULTS: VBD was confirmed in 66 lesions in 63 patients; 17 patients had confirmed atherosclerosis, and 22 had no lesions in the vertebrobasilar artery. Diagnostic performances of 2D-HRMRI (AUC, 0.839±0.04; sensitivity, 94.0; specificity, 79.5; diagnostic accuracy, 88.6) CE-iMSDE-3DMRI (AUC, 0.847±0.04; sensitivity, 84.8; specificity, 84.6; diagnostic accuracy, 84.7) and 2D-HRMRI+CE-iMSDE-3DMRI (AUC, 0.893±0.03; sensitivity, 97.0; specificity, 85.0; diagnostic accuracy, 92.5) were good. Comparisons of the diagnostic performance of 2D-HRMRI andCE-iMSDE-3DMRI showed that combined interpretation of 2D-HRMRI and iMSDE-3DMRI yields a significantly higher diagnostic performance than that of 2D-HRMRI (P=0.042). CONCLUSIONS: CE-iMSDE-3DMRI showed good diagnostic performance for the diagnosis of intracranial VBD. These results suggest that CE-iMSDE-3DMRI can be used in combination with 2D-HRMRI for the diagnosis of intracranial VBD.

Effect of microbial inoculants on fermentation quality and aerobic stability of sweet potato vine silage.

OBJECTIVE: This study was conducted to evaluate the effect of homo or hetero fermentative inoculants on fermentation quality and aerobic stability of sweet potato vine (SPV) silage containing Italian ryegrass hay as moisture absorbent. METHODS: The SPV was harvested at 15% dry matter, mixed with Italian ryegrass hay at 1:1 ratio on a fresh weight basis, and chopped to 3 to 5 cm length. After then, the chopped forage mixture was ensiled into 20-L mini silos in quadruplicate for 7, 48, and 100 days after application of microbial inoculants at 1.2×105 colony forming units (cfu)/g of forage following: no inoculant (CON), Lactobacillus plantarum as a homo fermentative (LP), Lactobacillus buchneri as a hetero fermentative (LB), and mixture of LP and LB at 1:1 ratio as a combo fermentative (MIX). RESULTS: The LP and MIX silages had lowest pH (p<0.001) on 7 and 48 days, while MIX and CON silages had greatest lactate concentrations (p<0.05) on 7 and 48 days, respectively. Acetate concentrations were highest (p<0.01) in LB and MIX silages on 7 days, and in LB silage on 48 days, while lactate to acetate ratios were lowest (p<0.001) in LB silages. The chemical compositions and nutrient digestibility of silage ensiled for 100 days was not affected by inoculants. On 100 days of ensiling, LB silage had lowest (p<0.01) lactate concentration and lactate to acetate ratio, but highest acetate concentration. Aerobic stability was highest (p<0.001) in LB silage followed in MIX silage. On contrast, LB silage had lowest (p<0.05) lactic acid bacteria and mold. CONCLUSION: The results indicated that application of LB solely had a better effect on aerobic stability than not only LP, but also MIX. However, LP application did not show beneficial effects from the viewpoints of fermentation quality and aerobic stability compared to CON.

Heart rate variability in leucine-rich repeat kinase 2-associated Parkinson's disease.

BACKGROUND: Heart rate variability is reduced in idiopathic PD, indicating cardiac autonomic dysfunction likely resulting from peripheral autonomic synucleinopathy. Little is known about heart rate variability in leucine-rich repeat kinase 2-associated PD. OBJECTIVES: This study investigated heart rate variability in LRRK2-associated PD. METHODS: Resting electrocardiograms were obtained from 20 individuals with LRRK2-associated PD, 37 nonmanifesting carriers, 48 related noncarriers, 26 idiopathic PD patients, and 32 controls. Linear regression modelling compared time and frequency domain values, adjusting for age, sex, heart rate, and disease duration. RESULTS: Low-frequency power and the ratio of low-high frequency power were reduced in idiopathic PD versus controls (P < .008, P < .029 respectively). In contrast, individuals with LRRK2-associated PD were not statistically different from controls in any parameter measured. Furthermore, all parameters trended toward being higher in LRRK2-associated PD when compared with idiopathic PD. CONCLUSIONS: Heart rate variability may remain intact in LRRK2-associated PD, adding to a growing literature supporting clinical-pathologic differences between LRRK2-associated and idiopathic PD. © 2017 International Parkinson and Movement Disorder Society.

Optimization of Transcutaneous Vagus Nerve Stimulation Using Functional MRI.

OBJECTIVE/HYPOTHESIS: Vagus nerve stimulation (VNS) is an established therapy for drug-resistant epilepsy, depression, and a number of other disorders. Transcutaneous stimulation of the auricular branch of the vagus nerve (tVNS) has been considered as a non-invasive alternative. Several functional magnetic resonance imaging (fMRI) studies on the effects of tVNS used different stimulation parameters and locations in the ear, which makes it difficult to determine the optimal tVNS methodology. The present study used fMRI to determine the most effective location for tVNS. MATERIALS AND METHODS: Four stimulation locations in the ear were compared: the inner tragus, inferoposterior wall of the ear canal, cymba conchae, and earlobe (sham). Thirty-seven healthy subjects underwent two 6-min tVNS stimulation runs per electrode location (monophasic rectangular 500 µs pulses, 25 Hz). General linear model was performed using SPM; region-of-interest analyses were performed for the brainstem areas. RESULTS: Stimulation at the ear canal resulted in the weakest activation of the nucleus of solitary tract (NTS), the recipient of most afferent vagal projections, and of the locus coeruleus (LC), a brainstem nucleus that receives direct input from the NTS. Stimulation of the inner tragus and cymba conchae activated these two nuclei as compared to sham. However, ROI analysis showed that only stimulation of the cymba conchae produced a significantly stronger activation in both the NTS and LC than did the sham stimulation. CONCLUSIONS: These findings suggest that tVNS at the cymba conchae properly activates the vagal pathway and results in its strongest activation, and thus may be the optimal location for tVNS therapies applied to the auricle.