The repertoire of G-protein-coupled receptors in Xenopus tropicalis

<p>Abstract</p> <p>Background</p> <p>The G-protein-coupled receptor (GPCR) superfamily represents the largest protein family in the human genome. These proteins have a variety of physiological functions that give them well recognized roles in clinical medicine. In <it>Xenopus tropicalis</it>, a widely used animal model for physiology research, the repertoire of GPCRs may help link the GPCR evolutionary history in vertebrates from teleost fish to mammals.</p> <p>Results</p> <p>We have identified 1452 GPCRs in the <it>X. tropicalis </it>genome. Phylogenetic analyses classified these receptors into the following seven families: <it>Glutamate</it>, <it>Rhodopsin</it>, <it>Adhesion</it>, <it>Frizzled</it>, <it>Secretin</it>, <it>Taste 2 </it>and <it>Vomeronasal 1</it>. Nearly 70% of <it>X. tropicalis </it>GPCRs are represented by the following three types of receptors thought to receive chemosensory information from the outside world: olfactory, vomeronasal 1 and vomeronasal 2 receptors.</p> <p>Conclusion</p> <p><it>X. tropicalis </it>shares a more similar repertoire of GPCRs with mammals than it does with fish. An examination of the three major groups of receptors related to olfactory/pheromone detection shows that in <it>X. tropicalis</it>, these groups have undergone lineage specific expansion. A comparison of GPCRs in <it>X. tropicalis</it>, teleost fish and mammals reveals the GPCR evolutionary history in vertebrates.</p

Research on Rainfall Intensity Threshold of Occasional Debris Flow Based on Infiltration

The rainfall warning method for debris flows usually uses rainfall intensity and duration to establish an I-D relationship internationally and determine the rainfall warning threshold for debris flows. This method requires extensive rainfall data from debris flow events in the study area to establish the I-D relationship. However, some areas with occasional debris flows lack sufficient debris flow events to establish I-D relationships to determine rainfall warning thresholds. Therefore, this study uses the infiltration effect of water flow on gravel soil and establishes a rainfall intensity threshold judgment formula for debris flow initiation based on the limit equilibrium method. Taking the Taiqing debris flow that occurred in Laoshan, China, on June 13, 2018, as an example, the rainfall intensity and characteristics of the debris flow are analyzed. The maximum rainfall intensity during this rainfall process far exceeds the rainfall intensity threshold determined by the judgment formula. Using the judgment formula, it can be determined that the rainfall process will cause debris flow. The judgment result is consistent with the actual situation (where a debris flow occurred during the rainfall process). To further verify the accuracy of the judgment formula, the rainfall process of Typhoon Lichma on August 11, 2019, in the study area was analyzed. The rainfall process has a long history. Still, the rainfall intensity is much lower than the threshold of rainfall intensity for the initiation of debris flow, so this rainfall will not cause the occurrence of debris flow. The judgment result is consistent with the actual situation (no debris flow occurred during rains). Doi: 10.28991/CEJ-2023-09-09-02 Full Text: PD

Calder\'on's commutator on Stratified Lie groups

Motivated by the recent work of Gimperlein and Goffeng on Calder\'on's commutator on compact Heisenberg type manifolds and the related weak Schatten class estimates, we establish the characterisation of $L^p$ boundedness for Calderon's commutator on stratified Lie groups. We further study the related weak Schatten class estimates on two step stratified Lie groups, which include the Heisenberg groups

Over-expression of human cytomegalovirus miR-US25-2-3p downregulates eIF4A1 and inhibits HCMV replication

AbstractIt has been reported that human cytomegalovirus (HCMV) miR-US25-2 reduces DNA viral replication including HCMV. However, the mechanism remains unknown. In our study, eukaryotic translation initiation factor 4A1 (eIF4A1) was identified to be a direct target of miR-US25-2-3p. Small interfering RNA (siRNA) and miR-US25-2-3p mediated eIF4A1 knockdown experiments revealed that high level of miR-US25-2-3p in MRC-5 cells decreased HCMV and host genomic DNA synthesis, and inhibited cap-dependent translation and host cell proliferation. However, eIF4A1 up-regulation induced by miR-US25-2-3p inhibitor increased HCMV copy number. Therefore, the over-expression of miR-US25-2-3p and consequent lower expression of eIF4A1 may contribute to the inhibition of HCMV replication

Characterization of the transcripts of human cytomegalovirus UL144

<p>Abstract</p> <p>Background</p> <p>The genome of human cytomegalovirus (HCMV) has been studied extensively, particularly in the UL/b' region. In this study, transcripts of one of the UL/b' genes, UL144, were identified in 3 HCMV isolates obtained from urine samples of congenitally infected infants.</p> <p>Methods</p> <p>Northern blot hybridization, cDNA library screening, and RACE-PCR were used.</p> <p>Results</p> <p>We identified at least 4 differentially regulated 3'-coterminal transcripts of UL144 in infected cells of 1,300, 1,600, 1,700, and 3,500 nucleotides (nt). The 1600 nt transcript was the major form of UL144 mRNA. The largest transcript initiated from the region within the UL141 open reading frame (ORF) and included UL141, UL142, UL143, UL144, and UL145 ORFs.</p> <p>Conclusions</p> <p>These findings reveal the complex nature of the transcription of the UL144 gene in clinical isolates.</p

Guanine nucleotide depletion inhibits pre-ribosomal RNA synthesis and causes nucleolar disruption

Inosine monophosphate dehydrogenase (IMPDH) is a pivotal enzyme in the de novo pathway of guanine nucleotide biosynthesis. Inhibitors of this enzyme decrease intracellular guanine nucleotide levels by 50-80% and have potential as anti-neoplastic agents. Both mycophenolic acid (MPA) and AVN-944 are highly specific inhibitors of IMPDH that cause cell cycle arrest or apoptosis in lymphocytes and leukemic cell lines. We have examined the mechanisms by which these two agents cause cytotoxicity. Both MPA and AVN-944 inhibit the growth of K562 cells, and induce apoptosis in Raji B and CCRF-CEM T cells. Both compounds strikingly inhibit RNA synthesis within 2 h of exposure. Depletion of guanine nucleotides by MPA and AVN-944 also causes an early and near-complete reduction in levels of the 45S precursor rRNA synthesis and the concomitant translocation of nucleolar proteins including nucleolin, nucleophosmin, and nucleostemin from the nucleolus to the nucleoplasm. This efflux correlates temporally with the sustained induction of p53 in cell lines with wild type p53. We conclude that inhibition of IMPDH causes a primary reduction in rRNA synthesis and secondary nucleolar disruption and efflux of nucleolar proteins that most likely mediate cell cycle arrest or apoptosis. The ability of AVN-944 to induce apoptosis in a number of leukemic cell lines supports its potential utility in the treatment of hematologic malignancies

Effect of grape pomace supplement on growth performance, gastrointestinal microbiota, and methane production in Tan lambs

Grape pomace (GP), a by-product in wine production, is nutritious and can be used as a feed ingredient for ruminants; however, its role in shaping sheep gastrointestinal tract (GIT) microbiota is unclear. We conducted a controlled trial using a randomized block design with 10 Tan lambs fed a control diet (CD) and 10 Tan lambs fed a pelleted diet containing 8% GP (dry matter basis) for 46 days. Rumen, jejunum, cecum, and colon bacterial and archaeal composition were identified by 16S rRNA gene sequencing. Dry matter intake (DMI) was greater (p &lt; 0.05) in the GP than CD group; however, there was no difference in average daily gain (ADG, p &lt; 0.05) and feed conversion ratio (FCR, p &lt; 0.05) between the two groups. The GP group had a greater abundance of Prevotella 1 and Prevotella 7 in the rumen; of Sharpe, Ruminococcaceae 2, and [Ruminococcus] gauvreauii group in the jejunum; of Ruminococcaceae UCG-014 and Romboutsia in the cecum, and Prevotella UCG-001 in the colon; but lesser Rikenellaceae RC9 gut group in the rumen and cecum, and Ruminococcaceae UCG-005 and Ruminococcaceae UCG-010 in the colon than the CD group. The pathways of carbohydrate metabolism, such as L-rhamnose degradation in the rumen, starch and glycogen degradation in the jejunum, galactose degradation in the cecum, and mixed acid fermentation and mannan degradation in the colon were up-graded; whereas, the pathways of tricarboxylic acid (TCA) cycle VIII, and pyruvate fermentation to acetone in the rumen and colon were down-graded with GP. The archaeal incomplete reductive TCA cycle was enriched in the rumen, jejunum, and colon; whereas, the methanogenesis from H2 and CO2, the cofactors of methanogenesis, including coenzyme M, coenzyme B, and factor 420 biosynthesis were decreased in the colon. The study concluded that a diet including GP at 8% DM did not affect ADG or FCR in Tan lambs. However, there were some potential benefits, such as enhancing propionate production by microbiota and pathways in the GIT, promoting B-vitamin production in the rumen, facilitating starch degradation and amino acid biosynthesis in the jejunum, and reducing methanogenesis in the colon

CDKL3 shapes immunosuppressive tumor microenvironment and initiates autophagy in esophageal cancer

BackgroundCDKL3 has been associated with the prognosis of several tumors. However, the potential role of CDKL3 in immunotherapy and the tumor microenvironment (TME) in esophageal carcinoma (ESCA) remains unclear.MethodsIn this study, Cox regression analysis was used to assess the predictive value of CDKL3 for ESCA outcomes. We systematically correlated CDKL3 with immunological features in the TME. The role of CDKL3 in predicting the efficacy of immunotherapy was also analyzed. Correlation analysis, Cox analysis and LASSO Cox regression were used to construct the CDKL3-related autophagy (CrA) risk score model. The relationship between CDKL3 expression and postoperative pathological complete response (pCR) rate in esophageal squamous cell carcinoma (ESCC) patients undergoing neoadjuvant chemoradiotherapy (nCRT) was evaluated using Immunohistochemical staining (IHC). The relationship between CDKL3 expression and autophagy induction was confirmed by immunofluorescence staining and western blot, and the effect of CDKL3 expression on macrophage polarization was verified by flow cytometry.ResultsHigh expression of CDKL3 was found in ESCA and was associated with poor prognosis in ESCA. Moreover, CDKL3 expression was negatively correlated with tumor-infiltrating immune cells (TIICs), the integrality of the cancer immunity cycles, and anti-tumor signatures, while CDKL3 expression was positively correlated with suppressive TME-related chemokines and receptors, immune hyperprogressive genes, and suppressive immune checkpoint, resulting in immunosuppressive TME formation in ESCA. An analysis of immunotherapy cohorts of the ESCA and pan-cancer showed a better response to immunotherapy in tumor patients with lower CDKL3 levels. The CrA risk score model was constructed and validated to accurately predict the prognosis of ESCA. Notably, the CrA risk score of ESCA patients was significantly positively correlated with M2 macrophages. Furthermore, knockdown CDKL3 in KYSE150 cells could inhibit autophagy induction and M2 macrophage polarization. And, radiation could downregulate CDKL3 expression and autophagy induction, while ESCC patients with high CDKL3 expression had a significantly lower response rate after nCRT than those with low CDKL3 expression.ConclusionCDKL3 may play an important role in anti-tumor immunity by regulating autophagy to promote the formation of immunosuppressive TME, thus playing a critical role in the prognosis of ESCA