Effect of age on the pathogenesis of Duck Tembusu virus in Cherry Valley ducks

The effect of host age on the outcome of Duck Tembusu virus (DTMUV) infection was studied in ducks. Three groups of Cherry Valley ducks at 1, 3 and 7 weeks of age were intramuscularly infected with DTMUV to systematically observe the clinical symptoms, pathological changes, tissue viral loads and immune responses. Severe clinical symptoms and neurological dysfunction were observed in 1-week-old ducks as early as 2 day post infection (dpi) and some died at 5 –7 dpi. Three week old ducks showed similar but milder symptoms and no deaths. However, 7-week-old ducks showed only transient loss of appetite. Gross lesions gradually reduced in severity as ducks matured. One week old ducks showed endocardial haemorrhage, splenomegaly, swelling in the lymph follicles of the ileum, liver and kidney swelling with degeneration, and meningeal hyperemia. Three week old ducks showed only mild pathological lesions. No visible lesions were observed in 7-week-old ducks. However, pathological histology analysis demonstrated all infected ducks displayed viral encephalitis. DTMUV could be detected in the brains of 1-week-old ducks as early as 1 dpi and virus titers of most organs in 1-week-old ducks were significantly higher than that of 3- and 7-week-old ducks at 3 –5 dpi. The patterns of IFN-γ, IL-2, and serum neutralizing antibodies were similar, and there were significant difference between the youngest ducks and the older ducks at early infection stage (P<0.05). More important is that although the antibody titers of all infected ducks were similar from 9 dpi to 17 dpi, reduced clearance of virus was observed in the youngest groups comparing with the other two groups, indicating that immune system maturity was more important than the presence of neutralizing antibody. In summary, this study demonstrates that viral pathogenesis is strongest in 1-week-old ducks and the age-related immune response plays an important role in the pathogenesis of DTMUV in ducks

Immune responses of ducks infected with duck Tembusu virus

Duck Tembusu virus (DTMUV) can cause serious disease in ducks, characterized by reduced egg production. Although the virus has been isolated and detection methods developed, the host immune responses to DTMUV infection are unclear. Therefore, we systematically examined the expression of immune-related genes and the viral distribution in DTMUV-infected ducks, using quantitative real-time PCR. Our results show that DTMUV replicates quickly in many tissues early in infection, with the highest viral titers in the spleen 1 day after infection. Rig-1, Mda5, and Tlr3 are involved in the host immune response to DTMUV, and the expression of proinflammatory cytokines (Il-1β, -2, -6, Cxcl8) and antiviral proteins (Mx, Oas, etc.) are also upregulated early in infection. The expression of Il-6 increased most significantly in the tissues tested. The upregulation of Mhc-I was observed in the brain and spleen, but the expression of Mhc-II was upregulated in the brain and downregulated in the spleen. The expression of the interferons was also upregulated to different degrees in the spleen but that of the brain was various. Our study suggests that DTMUV replicates rapidly in various tissues and that the host immune responses are activated early in infection. However, the overexpression of cytokines may damage the host. These results extend our understanding of the immune responses of ducks to DTMUV infection, and provide insight into the pathogenesis of DTMUV attributable to host factors

Are past and future symmetric in mental time line?

A growing body of evidence has suggested that time, from early to late, or from past to future, was represented in a spatially oriented mental time line. However, little is known about its characteristics. The present study provided the first empirical evidence to explore the symmetry of spatial representations of past and future in the mental time line. Specifically, we compared the Spatial-Temporal Association Response Codes (STARC) effects and distance effects of past and future in four experiments. Results showed that for near past and near future, STARC effects were similar (Experiment 1). For distant past, the STARC effect was significant, but not for distant future (Experiment 2). Furthermore, the distance effect in the past was significantly stronger than in the future (Experiment 3 and 4). These findings supported the idea that time points are not evenly distributed in mental time line. Spatial representations of the past and the future are asymmetric, and the spatial representation of past seems stronger than future. The logarithmic pattern of internal spatial representation of past or future is also discussed

Chemotherapy-Induced Peripheral Neurotoxicity and Complementary and Alternative Medicines: Progress and Perspective

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe and dose-limiting side effect of antineoplastic drugs. It can cause sensory, motor and autonomic system dysfunction, and ultimately force patients to discontinue chemotherapy. Until now, little is understood about CIPN and no consistent standard of care is available. Since CIPN is a multifactorial disease, the clinical efficacy of single pharmacological drugs is disappointing, prompting patients to seek out alternative treatment options. Complementary and alternative medicines (CAMs), especially herbal medicines, are well known for their multifaceted implications and widely used in human health care. So far, several phytochemicals, plant extracts, and herbal formulas have been evaluated for their possible therapeutic potential in preventing onset and progression of CIPN in experimental models. Clinical acupuncture has also been shown to improve CIPN symptoms. In this review, we will give an outline of our current knowledge on the research advances of CIPN, the role of CAMs in alleviating CIPN and possible lacunae in research that needs to be addressed

Expression of Immune-Related Genes of Ducks Infected with Avian Pathogenic Escherichia coli (APEC)

Avian pathogenic Escherichia coli (APEC) can cause severe disease in ducks, characterized by perihepatitis, pericarditis and airsacculitis. Although the studies of bacteria isolation and methods of detection have been reported, host immune responses to APEC infection remain unclear. In response, we systemically examined the expression of immune-related genes and bacteria distribution in APEC-infected ducks. Results demonstrated that APEC can quickly replicate in the liver, spleen and brain, with the highest bacteria content at 2 day post infection. The expression of Toll-like receptors (TLRs), avian β-defensins (AvBDs) and major histocompatibility complex (MHC) were tested in the liver, spleen and brain of infected ducks. TLR2, TLR4, TLR5 and TLR15 showed different expression patterns, which indicated that they all responded to APEC infection. The expression of AvBD2 was upregulated in all tested tissues during the 3 days of testing, whereas the expression of AvBD4, AvBD5, AvBD7 and AvBD9 were downregulated, and though MHC-I was upregulated on all test days, MHC-II was dramatically downregulated. Overall, our results suggest that APEC can replicate in various tissues in a short time, and the activation of host immune responses begins at onset of infection. These findings thus clarify duck immune responses to APEC infection and offer insights into its pathogenesis

Alpha-1 antitrypsin prevents the development of preeclampsia through suppression of oxidative stress

Preeclampsia (PE) and its complications have become the leading cause of maternal and fetal morbidity and mortality in the world. And the development of PE is still barely predictable and thus challenging to prevent and manage clinically. Oxidative stress contributes to the development of the disease. Our previous study demonstrated that exogenous Alpha-1 antitrypsin (AAT) played a cytoprotective role in vascular endothelial cell by suppressing oxidative stress. In this study, we aim to investigate whether AAT contributes to the development of PE, and to identify the mechanism behind these effects. We found that AAT levels were significantly decreased in placenta tissues from women with PE compared that of healthy women. Notably, we demonstrate that AAT injection is able to relieve the high blood pressure and reduce urine protein levels in a dose-dependent manner in PE mice. In addition, our results showed that AAT injection exhibited an anti-oxidative stress role by significantly reducing PE mediated-upregulation of ROS, MMP9 and MDA, and increasing the levels of SOD, eNOS and GPx with increased dosage of AAT. Furthermore, we found that AAT injection inactivated PE mediated activation of PAK/STAT1/p38 signaling. These findings were confirmed in human samples. In conclusion, our study suggests that exogenous AAT injection increases the antioxidants and suppresses oxidative stress, and subsequent prevention of PE development through inactivation of STAT1/p38 signaling. Thus, AAT would become a potential strategy for PE therapy

Anterior cingulate cortex-related connectivity in first-episode schizophrenia: a spectral dynamic causal modeling study with functional magnetic resonance imaging

Understanding the neural basis of schizophrenia (SZ) is important for shedding light on the neurobiological mechanisms underlying this mental disorder. Structural and functional alterations in the anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), hippocampus, and medial prefrontal cortex (MPFC) have been implicated in the neurobiology of SZ. However, the effective connectivity among them in SZ remains unclear. The current study investigated how neuronal pathways involving these regions were affected in first-episode SZ using functional magnetic resonance imaging (fMRI). Forty-nine patients with a first-episode of psychosis and diagnosis of SZ—according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision—were studied. Fifty healthy controls (HCs) were included for comparison. All subjects underwent resting state fMRI. We used spectral dynamic causal modeling (DCM) to estimate directed connections among the bilateral ACC, DLPFC, hippocampus, and MPFC. We characterized the differences using Bayesian parameter averaging (BPA) in addition to classical inference (t-test). In addition to common effective connectivity in these two groups, HCs displayed widespread significant connections predominantly involved in ACC not detected in SZ patients, but SZ showed few connections. Based on BPA results, SZ patients exhibited anterior cingulate cortico-prefrontal-hippocampal hyperconnectivity, as well as ACC-related and hippocampal-dorsolateral prefrontal-medial prefrontal hypoconnectivity. In summary, sDCM revealed the pattern of effective connectivity involving ACC in patients with first-episode SZ. This study provides a potential link between SZ and dysfunction of ACC, creating an ideal situation to associate mechanisms behind SZ with aberrant connectivity among these cognition and emotion-related regions

The time course of contextual effects on visual word recognition

Sentence comprehension depends on continuous prediction of upcoming words. However, when and how contextual information affects the bottom-up streams of visual word recognition is unknown. This study examined the effects of word frequency and contextual predictability (cloze probability of a target word embedded in the sentence) on N1, P200, and N400 components, which are related to various cognitive operations in early visual processing, perceptual decoding, and semantic processing. The data exhibited a significant interaction between predictability and frequency at the anterior N1 component. The predictability effect, in which the low predictability words elicited a more negative N1 than high predictability words, was only observed when reading a high frequency word. A significant predictability effect occurred during the P200 time window, in which the low predictability words elicited a less positive P200 than high predictability words. These data suggest that the contextual information facilitate visual-feature detection and orthographic pre-activation in the early stage of visual word processing. There is also a significant predictability effect on the N400 component; low predictability words elicited a greater N400 than high predictability words, although this effect did not interact with frequency. The temporal dynamics of the manner in which contextual information affects the visual word recognition is discussed. These findings support the interactive account, suggesting that contextual information facilitates visual-feature and orthographic processing in the early stage, and semantic integration in the later stage

NIRS-based hyperscanning reveals inter-brain neural synchronization during cooperative Jenga game with face-to-face communication

Functional near-infrared spectroscopy (fNIRS) is an increasingly popular technology for studying social cognition. In particular, fNIRS permits simultaneous measurement of hemodynamic activity in two or more individuals interacting in a naturalistic setting. Here, we used fNIRS hyperscanning to study social cognition and communication in human dyads engaged in cooperative and non-cooperative interaction while they played the game of Jenga™. Novel methods were developed to identify synchronized channels for each dyad and a structural node-based spatial registration approach was utilized for inter-dyad analyses. Strong inter-brain neural synchrony (INS) was observed in the posterior region of the right middle and superior frontal gyrus, in particular Brodmann area 8, during cooperative and obstructive interaction. This synchrony was not observed during the parallel game play condition and the dialogue section, suggesting that BA8 was involved in goal-oriented social interaction such as complex interactive movements and social decision-making. INS was also observed in the dorsomedial prefrontal region (dmPFC), in particular Brodmann 9, during cooperative interaction only. These additional findings suggest that BA9 may be particularly engaged when theory-of-mind is required for cooperative social interaction. The new methods described here have the potential to significantly extend fNIRS applications to social cognitive research