Anxiety is characterized by feelings of tension and worry even in the absence of threatening stimulus. Pathological condition of anxiety elicits defensive behavior and aversive reaction ultimately ...impacting individuals and society. The gut microbiota has been shown to contribute to the modulation of anxiety-like behavior in rodents through the gut-brain axis. Several studies observed that germ-free (GF) and the broad spectrum of antibiotic cocktail (ABX)-treated rodents display lowered anxiety-like behavior. We speculate that gut microbial short-chain fatty acids (SCFA) modulate the innate anxiety response. Herein, we administered SCFA in the drinking water in adult mice treated with ABX to deplete the microbiota and tested their anxiety-like behavior. To further augment the innate fear response, we enhanced the aversive stimulus of the anxiety-like behavior tests. Strikingly, we found that the anxiety-like behavior in ABX mice was not altered when enhanced aversive stimulus, while control and ABX mice supplemented with SCFA displayed increased anxiety-like behavior. Vagus nerve serves as a promising signaling pathway in the gut-brain axis. We determined the role of vagus nerve by subdiaphragmatic vagotomy (SDV) in ABX mice supplemented with SCFA. We found that the restored anxiety-like behavior in ABX mice by SCFA was unaffected by SDV. These findings suggest that gut microbiota can regulate anxiety-like behavior through their fermentation products SCFA.
This article is part of the Special Issue on ‘Microbiome & the Brain: Mechanisms & Maladies’.
•SCFA modulates innate anxiety response in mice in a microbiota-dependent manner.•Increased aversive stimulus enhances the innate anxiety response in SPF mice, but not in microbiome-depleted mice.•The decrease of anxiety-like behavior in microbiome-depleted mice can be restored by SCFA.•Periphery SCFA selectively down-regulates the endogenous levels of SCFA in serum and brain.•Vagus nerve is not required for the innate anxiety modulation by SCFA.
This paper documents that investors value unexpected changes in a firm's relative earnings performance (REP) in addition to its absolute earnings surprise on the firm's earnings announcement date. ...Consistent with REP filtering out industry-wide common shocks and conveying information about the firm's competitive advantage over its industry peers, investors react more strongly to unexpected relative earnings for firms with a stronger peer-firm earnings correlation and for firms with fewer growth options in their operations relative to their industry peers. Moreover, current unexpected REP is positively associated future growths in sales, market share, and earnings performance, suggesting that firms with stronger REP are better able to capture future industry opportunities.
Opioid dependence is currently one of the most serious problems affecting the social norms and public health system. Methadone maintenance therapy (MMT) is being widely used in treating ...heroin-dependent patients. The mechanism of methadone metabolism and disposition has been shown to involve cytochrome P450 (CYP450) and P-glycoprotein. The aim of this study was to explore the relationships among genetic polymorphisms, BMI and effective dose of methadone used in MMT within a northern Taiwan cohort.
One hundred heroin-dependent patients were enrolled in the study. The clinical data gathered included methadone dose, sex and BMI. DNA was collected from the oral swab of the participants to analyze the relevant alleles.
An effective methadone dose correlated with sex, BMI and the presence of ABCB1 2677GG (rs2032582) and CYP2B6 516GG (rs374527). Furthermore, the CYP2B6 516GG homozygote was related to a higher average dose of methadone (GG: 68.50 ± 32.43; GT: 52.28 ± 25.75; TT: 44.44 ± 29.64; P < 0.02), whereas the ABCB1 2677GG homozygote was related to a lower dose (GG: 51.09 ± 20.83; GT: 69.65 ± 37.51; TT: 62.52 ± 30.44; P < 0.05). We examined the predictive effect of polymorphisms combined with sex and BMI on methadone dose by conducting multiple linear regressions. Our data predicted the average dose of methadone in approximately 30% of heroin-dependent patients.
The interactions between genetic polymorphisms and clinical features proved useful in identifying the effective dose of MMT for heroin-dependent patients in Taiwan more precisely.
Abstract
One of the main challenges for the observation of a transient luminous event (TLE) is to observe TLEs in different emission bands. Here, we show TLEs recorded using the ISUAL 427.8 nm, 630 ...nm, N
2
1P (623–750 nm) and 762‐nm‐filtered imager, and we analyze the 630‐nm‐filtered, N
2
1P‐filtered, and 762‐nm‐filtered images of TLEs for estimating the N
2
(B
3
Π
g
) Boltzmann vibrational temperature in comparison with the theoretical N
2
1P spectrum. For ISUAL recorded sprites, the average brightness of N
2
1P (I
1p
), 762 nm (I
762
), and 630 nm (I
630
) emission was 2.3, 0.6, and 0.02 MR. The N
2
(B
3
Π
g
) vibrational temperatures (
T
v
) was estimated to be 2800 K, 3200 K, and 4300 K for multiband emission ratios of I
630
/I
1p
, I
630
/I
762
, and I
762
/I
1p
. For observed elves, the average brightness I
1p
, I
762
, and I
630
were 170, 50, and 3 kR. The estimated
T
v
values were 3700 K, 3700 K, and 3800 K for ratios I
630
/I
1p
, I
630
/I
762
, and I
762
/I
1p
. For observed gigantic jets, the derived
T
v
values were 3000–5000 K for a ratio I
762
/I
1p
. Through N
2
(B
3
Π
g
)
T
v
analyses from emission ratios of ISUAL multiband observation, we derived the N
2
(B
3
Π
g
) vibrational temperature that ranges between 3000 and 5000 K or higher in TLEs. Accuracy and variations of derived N
2
(B
3
Π
g
)
T
v
are also discussed while relative population of vibrational levels in the Boltzmann equilibrium are also compared with past spectra observation.
Key Points
ISUAL multiband measured emission ratios of 630 nm, N
2
1P (623–750 nm) and 762 nm emissions in transient luminous events are summarized
N
2
(B
3
Π
g
) vibrational temperatures are estimated using ISUAL measured emission ratios in transient luminous events
Altitude profiles of estimated N
2
(B
3
Π
g
) vibrational temperatures range between 3000 and 5000 K or higher in transient luminous events
Conventional orthogonal frequency division multiple access (OFDMA) burst construction methods can only support limited numbers of connections due to the map overhead and corresponding limitations in ...the numbers of orthogonal resources blocks, which limits the capacity of current 4G and the following 5th generation (5G) networks. This study therefore provides a novel OFDMA burst construction algorithm and enhanced burst indexing aware algorithm (EHA), which try to maximize the throughput while considering the subchannel diversity and optimizing burst indexing issues. The EHA not only allocates the subchannels with the best channel quality for each burst, but also groups the bursts to alleviate the MAP overhead. Simulation results showed that the EHA yields two times the throughput that has been achieved using previous algorithms under a heavy load. Two contributions of the EHA are: (1) the overhead of burst indexing decreases because massive numbers of connections can be accommodated by one burst; and (2) the overall throughput increases due to that one connection with large data transferring requirements can be split and distributed into several bursts and placed on the subchannels with good channel quality to adopt better modulation coding scheme (MCS), if the saved bandwidth in this burst construction is more than the increased overhead of burst indexing.
Mitochondrial dysfunction is associated with cardiovascular diseases and diabetes. Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling, and the abnormal ...proliferation, apoptosis and migration of pulmonary arterial smooth muscle cells (PASMCs). The glucagon-like peptide-1 (GLP-1) receptor agonist, liraglutide, has been shown to prevent pulmonary hypertension in monocrotaline-exposed rats. The aim of this study was to investigate the effect of liraglutide on autophagy, mitochondrial stress and apoptosis induced by platelet-derived growth factor BB (PDGF-BB). PASMCs were exposed to PDGF-BB, and changes in mitochondrial morphology, fusion-associated protein markers, and reactive oxygen species (ROS) production were examined. Autophagy was assessed according to the expressions of microtubule-associated protein light chain 3 (LC3)-II, LC3 puncta and Beclin-1. Western blot analysis was used to assess apoptosis, mitochondrial stress and autophagy markers. Liraglutide significantly inhibited PDGF-BB proliferation, migration and motility in PASMCs. PDGF-BB-induced ROS production was mitigated by liraglutide. Liraglutide increased the expression of α-smooth muscle actin (α-SMA) and decreased the expression of p-Yes-associated protein (p-YAP), inhibited autophagy-related protein (Atg)-5, Atg-7, Beclin-1 and the formation of LC3-β and mitochondrial fusion protein dynamin-related (Drp)1. Therefore, liraglutide can mitigate the proliferation of PASMCs via inhibiting cellular Drp1/nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) pathways and Atg-5/Atg-7/Beclin-1/LC3β-dependent pathways of autophagy in PAH.
Abstract Background context Previous studies on the risk and prevalence of diabetes among spinal cord injury (SCI) patients are limited and controversial. Purpose To compare the risk and incidence ...rate (IR) of Type 2 diabetes in SCI and non-SCI patients. Study design This is a population-based retrospective cohort study. Patient sample Data from Taiwan's National Health Insurance Research Database for the period 1997 to 2010 were analyzed. Patients aged 20 years and older newly identified with SCIs during this period were included in the SCI cohort. A non-SCI comparison cohort was randomly selected from National Health Insurance beneficiaries and matched with the SCI cohort based on age, sex, and index date. Outcome measures Both cohorts were followed until the first of the following occurred: the diagnosis of Type 2 diabetes (International Classification of Disease, Ninth Revision, Clinical Modification codes 250), withdrawal from the insurance system, the end of 2010, or death. Methods A Cox proportional hazards regression analysis was used to estimate the risk of developing diabetes. Results Taiwan possesses an older SCI population, with a mean age of 51.6 years. The IR for diabetes in patients with and without SCIs was 22.1 per 10,000 person-years and 17.2 per 10,000 person-years, respectively. The adjusted hazard ratio (HR) for diabetes was 1.33 times higher in patients with SCIs than in those without SCIs. In patients with SCIs, men (adjusted HR=1.23, 95% confidence interval (CI)=1.04–1.44), older people (adjusted HR=4.26 in patients older than 65 years, 95% CI=3.16–5.74), patients with comorbidity (adjusted HR=1.36, 95% CI=1.14–1.62), and patients with a complete thoracic SCI (T-spine injury) (adjusted HR=2.13, 95% CI=0.95–4.79) were more likely to be diagnosed with diabetes than other patient subgroups. Conclusions Our findings may facilitate the prioritizing of preventive health strategies and planning of long-term care for SCI patients.
This paper examines whether outstanding employee stock options (ESOs), which represent the firm's contractual obligation to deliver shares upon ESO exercise, affect firms' credit ratings. I ...hypothesize that outstanding ESOs play two information roles-(1) suggesting equity infusion, and (2) predicting share repurchases-that help credit-rating agencies evaluate the issuing company's debt service ability. Consistent with these hypothesized roles, results indicate that the present values of expected cash proceeds and tax benefits from ESO exercise have favorable effects on credit ratings. In contrast, the present value of the expected cost of ESO-related share repurchases has an unfavorable effect on credit ratings and this unfavorable effect is more pronounced for firms with a greater tendency to repurchase shares. The after-tax fair value of outstanding ESOs, which summarizes the effects of the above three ESO-related cash flows, is negatively associated with credit ratings. Taken together, these findings are consistent with credit-rating agencies incorporating the information conveyed by outstanding ESOs regarding potential equity infusion and ESO-related repurchases in their credit risk assessments and assigning lower credit ratings to firms with greater values of outstanding ESOs.
Approximately, 25% of nasopharyngeal carcinoma (NPC) patients develop recurrent disease. NPC may involve relatively few genomic alterations compared to other cancers due to its association with ...Epstein‐Barr virus (EBV). We envisioned that in‐depth sequencing of tumor tissues might provide new insights into the genetic alterations of this cancer. Thirty‐three NPC paired tumor/adjacent normal or peripheral blood mononuclear cell samples were deep‐sequenced (>1000×) with respect to a panel of 409 cancer‐related genes. Newly identified mutations and its correlation with clinical outcomes were evaluated. Profiling of somatic mutations and copy number variations (CNV) in NPC tumors identified alterations in RTK/RAS/PI3K, NOTCH, DNA repair, chromatin remodeling, cell cycle, NF‐κB, and TGF‐β pathways. In addition, patients harbored CNV among 409 cancer‐related genes and missense mutations in TGF‐β/SMAD signaling were associated with poor overall survival and poor recurrence‐free survival, respectively. The CNV events were correlated with plasma EBV copies, while mutations in TGFBR2 and SMAD4 abrogate SMAD‐dependent TGF‐β signaling. Functional analysis revealed that the new TGFBR2 kinase domain mutants were incapable of transducing the signal, leading to failure of phosphorylation of SMAD2/3 and activation of downstream TGF‐β‐mediated cell growth arrest. This study provides evidence supporting CNV and dysregulated TGF‐β signaling contributes to exacerbating the NPC pathogenesis.
Profiling of somatic mutations and copy number variations (CNV) in NPC tumors identified alterations in RTK/RAS/PI3K, NOTCH, DNA repair, chromatin remodeling, cell cycle, NF‐κB, and TGF‐β pathways. Among them, TGFBR2 loss‐of‐function mutations are resistant to TGF‐β‐induced growth inhibition. This study provides evidence supporting CNV and dysregulated TGF‐β signaling contributes to exacerbating the NPC pathogenesis.
Two types of racemic rodlike Schiff base mesogens with –CN– (type I ) and –NC– (type III ) linkages were prepared. These mesogens possessed either difluoro substitutions at the inner-core position ...of the phenyl ring or hydroxy group to form intramolecular hydrogen bonding with an ester or/and imine linkage. When the appropriate concentration of chiral additive is doped into them, the incorporation of two fluoro substituents is more useful for blue phase (BP) stabilization than that of a hydroxy group near the ester linkage in Schiff base mesogens. BPI and BPII can be identified by reflectance spectra and polarized optical microscope images. BPII emerges easily on cooling when the appropriate chiral dopant ISO(6OBA)2 or chiral dopant S811 is doped into the Schiff base mesogen having only a hydroxy group near the ester linkage. Interestingly, BPI can be observed when 10–15 wt% ISO(6OBA)2 was doped into the difluoro substituted Schiff base mesogen III during a heating process. The experimental and molecular modeling results indicate that most of the difluorinated Schiff base mesogens with larger dipole moments exhibit wider BP ranges than their corresponding non-fluorinated homologues under the same chirality condition. In addition, wide BPs can be induced for racemic rodlike Schiff base mesogens I in the chiral system and this is easier than that for racemic rodlike Schiff base mesogens III . In Schiff base mesogens I , the dipole moment is dominant for BP stabilization. However, the fluorine substituent effect is the main factor in Schiff base mesogens III .
PDF
