Abnormal Transcript Levels of Cytokines Among Iranian COVID-19 Patients

The members of the ZC3H12/MCPIP/Regnase family of RNases have emerged as important regulators of inflammation. In contrast to Regnase-1, -2 and -4, a thorough characterization of Regnase-3 (Reg-3) has not yet been explored. Here we demonstrate that Reg-3 differs from other family members in terms of NYN/PIN domain features, cellular localization pattern and substrate specificity. Together with Reg-1, the most comprehensively characterized family member, Reg-3 shared IL-6, IER-3 and Reg-1 mRNAs, but not IL-1β mRNA, as substrates. In addition, Reg-3 was found to be the only family member which regulates transcript levels of TNF, a cytokine implicated in chronic inflammatory diseases including psoriasis. Previous meta-analysis of genome-wide association studies revealed Reg-3 to be among new psoriasis susceptibility loci. Here we demonstrate that Reg-3 transcript levels are increased in psoriasis patient skin tissue and in an experimental model of psoriasis, supporting the immunomodulatory role of Reg-3 in psoriasis, possibly through degradation of mRNA for TNF and other factors such as Reg-1. On the other hand, Reg-1 was found to destabilize Reg-3 transcripts, suggesting reciprocal regulation between Reg-3 and Reg-1 in the skin. We found that either Reg-1 or Reg-3 were expressed in human keratinocytes in vitro. However, in contrast to robustly upregulated Reg-1 mRNA levels, Reg-3 expression was not affected in the epidermis of psoriasis patients. Taken together, these data suggest that epidermal levels of Reg-3 are negatively regulated by Reg-1 in psoriasis, and that Reg-1 and Reg-3 are both involved in psoriasis pathophysiology through controlling, at least in part different transcripts.

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Nucleotide-Binding Leucine-Rich Repeat Genes CsRSF1 and CsRSF2 Are Positive Modulators in the Cucumis sativus Defense Response to Sphaerotheca fuliginea

International Journal of Molecular Sciences ◽

10.3390/ijms22083986 ◽

2021 ◽

Vol 22 (8) ◽

pp. 3986

Author(s):

Xue Wang ◽

Qiumin Chen ◽

Jingnan Huang ◽

Xiangnan Meng ◽

Na Cui ◽

...

Keyword(s):

Cell Membrane ◽

Defense Response ◽

Nucleotide Binding ◽

Plant Defense Response ◽

Sphaerotheca Fuliginea ◽

Leucine Rich Repeat ◽

Transcript Levels ◽

Yield And Quality ◽

Leucine Rich Repeats ◽

Exogenous Substances

Cucumber powdery mildew caused by Sphaerotheca fuliginea is a leaf disease that seriously affects cucumber’s yield and quality. This study aimed to report two nucleotide-binding site-leucine-rich repeats (NBS-LRR) genes CsRSF1 and CsRSF2, which participated in regulating the resistance of cucumber to S. fuliginea. The subcellular localization showed that the CsRSF1 protein was localized in the nucleus, cytoplasm, and cell membrane, while the CsRSF2 protein was localized in the cell membrane and cytoplasm. In addition, the transcript levels of CsRSF1 and CsRSF2 were different between resistant and susceptible cultivars after treatment with exogenous substances, such as abscisic acid (ABA), methyl jasmonate (MeJA), salicylic acid (SA), ethephon (ETH), gibberellin (GA) and hydrogen peroxide (H2O2). The expression analysis showed that the transcript levels of CsRSF1 and CsRSF2 were correlated with plant defense response against S. fuliginea. Moreover, the silencing of CsRSF1 and CsRSF2 impaired host resistance to S. fuliginea, but CsRSF1 and CsRSF2 overexpression improved resistance to S. fuliginea in cucumber. These results showed that CsRSF1 and CsRSF2 genes positively contributed to the resistance of cucumber to S. fuliginea. At the same time, CsRSF1 and CsRSF2 genes could also regulate the expression of defense-related genes. The findings of this study might help enhance the resistance of cucumber to S. fuliginea.

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Development of antisense-mediated myostatin knockdown for the treatment of insulin resistance

Scientific Reports ◽

10.1038/s41598-021-81222-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Wouter Eilers ◽

Mark Cleasby ◽

Keith Foster

Keyword(s):

Glucose Uptake ◽

Muscle Mass ◽

Exon Skipping ◽

Negative Regulator ◽

Intramuscular Administration ◽

Transcript Levels ◽

Muscle Disorders ◽

Intravenous Injections ◽

Phosphorodiamidate Morpholino Oligomers

AbstractMyostatin is a negative regulator of muscle mass and its inhibition represents a promising strategy for the treatment of muscle disorders and type 2 diabetes. However, there is currently no clinically effective myostatin inhibitor, and therefore novel methods are required. We evaluated the use of antisense phosphorodiamidate morpholino oligomers (PMO) to reduce myostatin expression in skeletal muscle and measured their effects on muscle mass and glucose uptake. C57/Bl6 mice received intramuscular or intravenous injections of anti-myostatin PMOs. Repeated intramuscular administration lead to a reduction in myostatin transcript levels (~ 20–40%), and an increase in muscle mass in chow and high-fat diet (HFD)-fed mice, but insulin-stimulated glucose uptake was reduced in PMO-treated muscles of HFD-fed mice. Five weekly intravenous administrations of 100 nmol PMO did not reduce myostatin expression, and therefore had no significant physiological effects. Unexpectedly, exon skipping levels were higher after intramuscular administration of PMO in HFD- than chow-fed mice. These results suggest that a modest PMO-induced reduction in myostatin transcript levels is sufficient to induce an increase in muscle mass, but that a greater degree of inhibition may be required to improve muscle glucose uptake.

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Enantioselective Effect of Flutriafol on Growth, Deoxynivalenol Production, and TRI Gene Transcript Levels in Fusarium graminearum

Journal of Agricultural and Food Chemistry ◽

10.1021/acs.jafc.0c06800 ◽

2021 ◽

Vol 69 (5) ◽

pp. 1684-1692

Author(s):

Chaofeng Li ◽

Shuai Fan ◽

Yan Wen ◽

Zhenchao Tan ◽

Chenglan Liu

Keyword(s):

Fusarium Graminearum ◽

Gene Transcript ◽

Transcript Levels

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Toward an Automatic Quality Assessment of Voice-Based Telemedicine Consultations: A Deep Learning Approach

Sensors ◽

10.3390/s21093279 ◽

2021 ◽

Vol 21 (9) ◽

pp. 3279

Author(s):

Maria Habib ◽

Mohammad Faris ◽

Raneem Qaddoura ◽

Manal Alomari ◽

Alaa Alomari ◽

...

Keyword(s):

Neural Networks ◽

Deep Learning ◽

Quality Assessment ◽

Transcript Level ◽

Assessment Process ◽

Classification Model ◽

Systematic Evaluation ◽

Transcript Levels ◽

Perceptual Evaluation

Maintaining a high quality of conversation between doctors and patients is essential in telehealth services, where efficient and competent communication is important to promote patient health. Assessing the quality of medical conversations is often handled based on a human auditory-perceptual evaluation. Typically, trained experts are needed for such tasks, as they follow systematic evaluation criteria. However, the daily rapid increase of consultations makes the evaluation process inefficient and impractical. This paper investigates the automation of the quality assessment process of patient–doctor voice-based conversations in a telehealth service using a deep-learning-based classification model. For this, the data consist of audio recordings obtained from Altibbi. Altibbi is a digital health platform that provides telemedicine and telehealth services in the Middle East and North Africa (MENA). The objective is to assist Altibbi’s operations team in the evaluation of the provided consultations in an automated manner. The proposed model is developed using three sets of features: features extracted from the signal level, the transcript level, and the signal and transcript levels. At the signal level, various statistical and spectral information is calculated to characterize the spectral envelope of the speech recordings. At the transcript level, a pre-trained embedding model is utilized to encompass the semantic and contextual features of the textual information. Additionally, the hybrid of the signal and transcript levels is explored and analyzed. The designed classification model relies on stacked layers of deep neural networks and convolutional neural networks. Evaluation results show that the model achieved a higher level of precision when compared with the manual evaluation approach followed by Altibbi’s operations team.

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An ER–Golgi Tethering Factor SLOH4/MIP3 Is Involved in Long-term Heat Tolerance of Arabidopsis

Plant and Cell Physiology ◽

10.1093/pcp/pcaa157 ◽

2020 ◽

Author(s):

Kazuho Isono ◽

Ryo Tsukimoto ◽

Satoshi Iuchi ◽

Akihisa Shinozawa ◽

Izumi Yotsui ◽

...

Keyword(s):

Heat Stress ◽

Heat Tolerance ◽

Secretory Proteins ◽

Wild Type ◽

Additional Function ◽

Transcript Levels ◽

Unfolded Protein ◽

In The Wild ◽

Protein Response

Abstract Plants are often exposed not only to short-term (S-) heat stress but also to diurnal long-term (L-) heat stress over several consecutive days. To reveal the mechanisms underlying L-heat stress tolerance, we here used a forward genetic screening for sensitive to long-term heat (sloh) mutants and isolated sloh4. The mutant was hypersensitive to L- but not S-heat stress. The causal gene of sloh4 was identical to MIP3 encoding a member of the MAIGO2 (MAG2) tethering complex, which is composed of the MAG2, MIP1, MIP2, and MIP3 subunits and is localized at the endoplasmic reticulum (ER) membrane. Although sloh4/mip3 was hypersensitive to L-heat stress, the sensitivity of the mag2-3 and mip1–1 mutants was similar to that of the wild type. Under L-heat stress, the ER stress and the following unfolded protein response (UPR) were more pronounced in sloh4 than in the wild type. Transcript levels of bZIP60-regulated UPR genes were strongly increased in sloh4 under L-heat stress. Two processes known to be mediated by INOSITOL REQUIRING ENZYME1 (IRE1)—accumulation of the spliced bZIP60 transcript and a decrease in the transcript levels of PR4 and PRX34, encoding secretory proteins—were observed in sloh4 in response to L-heat stress. These findings suggest that misfolded proteins generated in sloh4 under L-heat stress may be recognized by IRE1 but not bZIP28, resulting in initiation of the UPR via activated bZIP60. Therefore, it would be possible that only MIP3 in MAG2 complex has an additional function in L-heat tolerance, which is not related to the ER–Golgi vesicle tethering.

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