Speech motor adaptation during synchronous and metronome-timed speech.

Sensorimotor integration during speech has been investigated by altering the sound of a speaker's voice in real time; in response, the speaker learns to change their production of speech sounds in order to compensate (adaptation). This line of research has however been predominantly limited to very simple speaking contexts, typically involving (a) repetitive production of single words and (b) production of speech while alone, without the usual exposure to other voices. This study investigated adaptation to a real-time perturbation of the first and second formants during production of sentences either in synchrony with a prerecorded voice (synchronous speech group) or alone (solo speech group). Experiment 1 (n = 30) found no significant difference in the average magnitude of compensatory formant changes between the groups; however, synchronous speech resulted in increased between-individual variability in such formant changes. Participants also showed acoustic-phonetic convergence to the voice they were synchronizing with prior to introduction of the feedback alteration. Furthermore, the extent to which the changes required for convergence agreed with those required for adaptation was positively correlated with the magnitude of subsequent adaptation. Experiment 2 tested an additional group with a metronome-timed speech task (n = 15) and found a similar pattern of increased between-participant variability in formant changes. These findings demonstrate that speech motor adaptation can be measured robustly at the group level during performance of more complex speaking tasks; however, further work is needed to resolve whether self-voice adaptation and other-voice convergence reflect additive or interactive effects during sensorimotor control of speech. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Arginine regulates inflammation response-induced by Fowl Adenovirus serotype 4 via JAK2/STAT3 pathway.

BACKGROUND: Fowl Adenovirus serotype 4 (FAdV-4) infection causes severe inflammatory response leading to hepatitis-hydropericardium syndrome (HHS) in poultry. As an essential functional amino acid of poultry, arginine plays a critical role in anti-inflammatory and anti-oxidative stress. RESULTS: In this study, the differential expression genes (DEGs) were screened by transcriptomic techniques, and the DEGs in gene networks of inflammatory response-induced by FAdV-4 in broiler's liver were analyzed by Kyoto encyclopedia of genes and genomes (KEGG) enrichment. The results showed that the cytokines pathway and JAK/STAT pathway were significantly enriched, in which the DEGs levels of IL-6, IL-1ß, IFN-α, JAK and STAT were significantly up-regulated after FAdV-4 infection. It was further verified with real-time fluorescence quantitative polymerase chain reaction (Real-time qPCR) and Western blotting (WB) in vitro and in vivo. The findings demonstrated that FAdV-4 induced inflammatory response and activated JAK2/STAT3 pathway. Furthermore, we investigated whether arginine could alleviate the liver inflammation induced by FAdV-4. After treatment with 1.92% arginine level diet to broilers or 300 µg/mL arginine culture medium to LMH cell line with FAdV-4 infection at the same time, we found that the mRNA levels of IL-6, IL-1ß, IFN-α and the protein levels of p-JAK2, p-STAT3 were down-regulated, compared with FAdV-4 infection group. Furthermore, we confirmed that the inflammation induced by FAdV-4 was ameliorated by pre-treatment with JAK inhibitor AG490 in LMH cells, and it was further alleviated in LMH cells treatment with AG490 and ARG. CONCLUSIONS: These above results provide new insight that arginine protects hepatocytes against inflammation induced by FAdV-4 through JAK2/STAT3 signaling pathway.

Importin alpha 1 is required for the nucleus entry of Fowl Adenovirus serotype 4 Fiber-1 protein.

Fiber-1 protein (F1) is the structural protein of Fowl Adenovirus serotype 4 (FAdV-4), which could recondite the receptors of host cytomembrane. In this study, we firstly determined that F1 protein located in nucleus of LMH cells after infection with FAdV-4. We additionally revealed that F1 protein had a classic NLS, and the NLS was required for F1 nucleus entry, which was intently associated to the 26th Pro in NLS. The time rule result indicated that some F1 proteins firstly positioned in the nucleus 6 h posttranfection, and it entirely located in the nucleus 12 h posttranfection, then it ordinarily placed in cytoplasm 18 h posttranfection by means of microscopic fluorescence observation and Western Blotting. Then after transfection with pCI-neo-flag-F1 or infection with FAdV-4, the importin alpha 1 was once investigated whether or not it was required for F1 protein nucleus entry through immunofluorescence and/or Co-IP, results demonstrated that the F1 protein and importin alpha 1 co-located in the nucleus 6 h and 12 h posttranfection. The tiers of F1 protein vicinity in nucleus have been additionally investigated after knockdown expression or overexpression of importin alpha 1, and the results further revealed that importin alpha 1 used to be required for F1 protein nucleus entry. Finally, the function of F1 protein nucleus entry was investigated by qPCR, RT-PCR and Western Blotting, and the results revealed that F1 protein nucleus location was conducive to the proliferation of FAdV-4. In summary, we firstly reveal that the F1 protein of FAdV-4 locates in nucleus infected with FAdV-4, and confirm that importin alpha 1 binds to the NLS of F1 protein to nucleus localization, which promotes the proliferation of FAdV-4.

Regulation of Iron Homeostasis and Related Diseases.

The liver is the organ for iron storage and regulation; it senses circulating iron concentrations in the body through the BMP-SMAD pathway and regulates the iron intake from food and erythrocyte recovery into the bloodstream by secreting hepcidin. Under iron deficiency, hypoxia, and hemorrhage, the liver reduces the expression of hepcidin to ensure the erythropoiesis but increases the excretion of hepcidin during infection and inflammation to reduce the usage of iron by pathogens. Excessive iron causes system iron overload; it accumulates in never system and damages neurocyte leading to neurodegenerative diseases such as Parkinson's syndrome. When some gene mutations affect the perception of iron and iron regulation ability in the liver, then they decrease the expression of hepcidin, causing hereditary diseases such as hereditary hemochromatosis. This review summarizes the source and utilization of iron in the body, the liver regulates systemic iron homeostasis by sensing the circulating iron concentration, and the expression of hepcidin regulated by various signaling pathways, thereby understanding the pathogenesis of iron-related diseases.

Fowl Adenovirus Serotype 4 Influences Arginine Metabolism to Benefit Replication.

Hydropericardium syndrome (HPS) is caused by fowl adenovirus serotype 4 (FAdV-4). HPS has caused outbreaks in Chinese populations of broiler chickens since 2015. However, little is known about the molecular mechanisms underlying HPS. In this study, we used transcriptomic analysis to screen differentially expressed genes (DEGs) in the livers of FAdV-4-infected and noninfected chicks. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the gene network associated with the arginine metabolism pathway was enriched in livers infected by FAdV-4; 10 genes were downregulated and 8 genes were upregulated in these livers when compared to noninfected livers. The DEGs identified in livers were reanalyzed by real-time fluorescence quantitative PCR (qPCR); results indicated that the mRNA levels of the DEGs concurred with the data derived from KEGG analysis. Next, we used qPCR to detect the DEGs of the arginine metabolism pathway in a hepatocellular carcinoma cell line (LMH) after infection with FAdV-4 for 24 hr; this also indicated that the mRNA levels of the DEGs concurred with that seen in the liver. We also used si-RNA oligonucleotides to knock down the mRNA levels of iNOS in LMH cells infected with FAdV-4 and found that the viral load of FAdV-4 was increased. Further investigation revealed that the addition of 240 µg/ml of arginine into the culture medium of LMH cells infected with FAdV-4 for 24 hr led to a significant increase in the mRNA levels of iNOS but a significant reduction in the viral load of FAdV-4. Therefore, our data indicated that when broiler chickens become infected with FAdV-4, the arginine metabolic pathway in the liver becomes dysfunctional and the iNOS mRNA level decreases. This will add benefit to the replication of FAdV-4 but can be inhibited by the addition of an appropriate amount of arginine.

El adenovirus del pollo serotipo 4 influye en el metabolismo de la arginina para favorecer su replicación. El síndrome de hidropericardio (HPS) es causado por el adenovirus del pollo serotipo 4 (FAdV-4). Este síndrome ha causado brotes en las poblaciones de pollo de engorde en China desde 2015. Sin embargo, se conoce poco sobre los mecanismos moleculares subyacentes al hidropericardio. En este estudio, se utilizó el análisis transcriptómico para seleccionar genes expresados en forma diferencial (DEGs) en los hígados de pollos infectados y no infectados con el adenovirus serotipo 4. El análisis mediante la Enciclopedia de Genes and Genomas de Kyoto (KEGG) mostró que la red de genes asociada con la ruta del metabolismo de la arginina se enriqueció en hígados infectados por el adenovirus serotipo 4. Diez genes fueron regulados a la baja y ocho genes fueron regulados a la alta en estos hígados en comparación con los hígados de aves no infectadas. Los genes expresados en forma diferencial identificados en los hígados se volvieron a analizar mediante un método cuantitativo de PCR de fluorescencia en tiempo real (qPCR). Los resultados indicaron que los niveles de ARNm de los genes expresados en forma diferencial coincidían con los datos derivados del análisis la Enciclopedia de Genes and Genomas de Kyoto. Posteriormente, se utilizó qPCR para detectar los genes expresados en forma diferencial de la vía del metabolismo de la arginina en una línea celular de carcinoma hepatocelular (LMH) infectadas con el adenovirus del pollo serotipo 4 durante 24 horas. Esto también indicó que los niveles de ARNm de los genes expresados en forma diferencial coincidían con los observados en el hígado. También se utilizaron oligonucleótidos de ARN para bloquear los niveles de ARN mensajero de iNOS en células LMH infectadas con el adenovirus del pollo serotipo 4 y se descubrió que la carga viral del adenovirus aumentó. La investigación adicional reveló que la adición de 240 µg/ml de arginina en el medio de cultivo de las células LMH infectadas con el adenovirus serotipo 4 durante 24 horas condujo a un aumento significativo en los niveles de ARN mensajero de iNOS pero con una reducción significativa en la carga viral del adenovirus serotipo 4 Por lo tanto, estos datos indican que cuando los pollos de engorde se infectan con adenovirus del pollo serotipo 4, la vía metabólica de la arginina en el hígado se vuelve disfuncional y el nivel de ARN mensajero de iNOS disminuye. Esto favorecerá la replicación del adenovirus del pollo serotipo 4, pero puede inhibirse mediante la adición de una cantidad adecuada de arginina.

Transcriptome Analysis Reveals New Insight of Fowl Adenovirus Serotype 4 Infection.

Since 2015, Fowl adenovirus serotype 4 (FAdV-4) infection has caused serious economic losses to the poultry industry worldwide. We isolated and identified the FAdV-4 strain NP, from infected chickens on a layer farm, using chicken embryo allantoic cavity inoculation, electron microscopy, viral genome sequencing, and regression analysis. To explore the pathogenesis of FAdV-4 infection, we conducted transcriptome sequencing analysis of the liver in chickens infected with FAdV-4, using the Illumina® HiSeq 2000 system. Two days after infection with the FAdV-4 NP strain, 13,576 differentially expressed genes (DEGs) were screened in the liver, among which, 7,480 were up-regulated and 6,096 were down-regulated. Gene ontology (GO) analysis indicated that these genes were involved in 52 biological functions. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that those DEGs were involved in 33 pathways. We then focused on the KEGG pathway of phagosome and found that mRNA levels of the 25 DEGs in that pathway were up-regulated, and seven DEGs were down-regulated. Real-time quantitative polymerase chain reaction (qPCR) confirmed the accuracy and reliability of these findings. Moreover, 24 h after LMH cells were infected with FAdV-4, the mRNA levels of F-actin, Rab7, TUBA, and DVnein were significantly increased. These four genes were all subsequently silenced by RNA interference, and viral replication of FAdV-4 was then significantly down-regulated. These findings demonstrate the isolation and identification of the FAdV-4 NP strain, and the DEGs in KEGG pathway of phagosome were utilized by FAdV-4 to benefit its infection.

Dietary supplementation with bovine lactoferrampin-lactoferricin produced by Pichia pastoris fed-batch fermentation affects intestinal microflora in weaned piglets.

This work is aimed at investigating the effects of recombinant bovine lactoferrampin-lactoferricin (LFA-LFC) instead of chlortetracycline on intestinal microflora in weaned piglets. The high cost of peptide production from either native digestion or chemical synthesis limits the clinical application of antimicrobial peptides. The expression of recombinant peptides in yeast may be an effective alternative. In the current study, recombinant LFA-LFC was produced via fed-batch fermentation in recombinant strain Pichia pastoris (KM71) XS10. Uniform design U6(6(4)) was used to optimize the fermentation conditions. The target peptide purified via cation-exchange and size-exclusion chromatography was added into the dietary of weaned piglets. After 21 days, the Lactobacilli, Bifidobacteria, and Enterobacteria in the chyme of the gut were quantified using real-time polymerase chain reaction. The results showed that approximately 82 mg of LFA-LFC was secreted into 1 L of medium under optimized conditions. Moreover, purified peptide showed strong antimicrobial activities against all the tested microorganisms. Compared with the control group, the LFA-LFC group increased the amount of Lactobacilli and Bifidobacteria (P<0.05) in the chyme of the stomach, duodenum, jejunum, ileum, colon, and caecum. These results show that dietary supplementation with LFA-LFC can affect intestinal microflora in weaned piglets.

Impaired translation initiation activation and reduced protein synthesis in weaned piglets fed a low-protein diet.

Weanling mammals (including infants) often experience intestinal dysfunction when fed a high-protein diet. Recent work with the piglet (an animal model for studying human infant nutrition) shows that reducing protein intake can improve gut function during weaning but compromises the provision of essential amino acids (EAA) for muscle growth. The present study was conducted with weaned pigs to test the hypothesis that supplementing deficient EAA (Lys, Met, Thr, Trp, Leu, Ile and Val) to a low-protein diet may maintain the activation of translation initiation factors and adequate protein synthesis in tissues. Pigs were weaned at 21 days of age and fed diets containing 20.7, 16.7 or 12.7% crude protein (CP), with the low-CP diets supplemented with EAA to achieve the levels in the high-CP diet. On Day 14 of the trial, tissue protein synthesis was determined using the phenylalanine flooding dose method. Reducing dietary CP levels decreased protein synthesis in pancreas, liver, kidney and longissimus muscle. A low-CP diet reduced the phosphorylation of eukaryotic initiation factor (eIF) 4E-binding protein-1 (4E-BP1) in skeletal muscle and liver while increasing the formation of an inactive eIF4E.4E-BP1 complex in muscle. Dietary protein deficiency also decreased the phosphorylation of mammalian target of rapamycin (mTOR) and the formation of an active eIF4E.eIF4G complex in liver. These results demonstrate for the first time that chronic feeding of a low-CP diet suppresses protein synthesis in animals partly by inhibiting mTOR signaling. Additionally, our findings indicate that supplementing deficient EAA to low-protein diets is not highly effective in restoring protein synthesis or whole-body growth in piglets. We suggest that conditionally essential amino acids (e.g., glutamine and arginine) may be required to maintain the activation of translation initiation factors and optimal protein synthesis in neonates.