Prediction of Hormone-Binding Proteins Based on K-mer Feature Representation and Naive Bayes

Hormone binding protein (HBP) is a soluble carrier protein that interacts selectively with different types of hormones and has various effects on the body’s life activities. HBPs play an important role in the growth process of organisms, but their specific role is still unclear. Therefore, correctly identifying HBPs is the first step towards understanding and studying their biological function. However, due to their high cost and long experimental period, it is difficult for traditional biochemical experiments to correctly identify HBPs from an increasing number of proteins, so the real characterization of HBPs has become a challenging task for researchers. To measure the effectiveness of HBPs, an accurate and reliable prediction model for their identification is desirable. In this paper, we construct the prediction model HBP_NB. First, HBPs data were collected from the UniProt database, and a dataset was established. Then, based on the established high-quality dataset, the k-mer (K = 3) feature representation method was used to extract features. Second, the feature selection algorithm was used to reduce the dimensionality of the extracted features and select the appropriate optimal feature set. Finally, the selected features are input into Naive Bayes to construct the prediction model, and the model is evaluated by using 10-fold cross-validation. The final results were 95.45% accuracy, 94.17% sensitivity and 96.73% specificity. These results indicate that our model is feasible and effective.

RNA Interference Suppression of v-ATPase B and Juvenile Hormone Binding Protein Genes Through Topically Applied dsRNA on Tomato Leaves: Developing Biopesticides to Control the South American Pinworm, Tuta absoluta (Lepidoptera: Gelechiidae)

The South American pinworm Tuta absoluta (Meyrick) (Family: Gelechiidae) is one of the most devastating lepidopteran pests in the developing countries of South America, Africa, and Asia. This pest is classified as the most serious threat for tomato production worldwide. In the present study, we analyzed RNAi-mediated control through exogenously applied dsRNA delivery on tomato. The dsRNA treatments were made to target the juvenile hormone binding protein and the v-ATPase B. Both mRNA targets were cloned, validated by sequencing, and used to produce each dsRNA. After treatments the relative transcript expression was analyzed using qRTPCR to assess to efficacy of RNAi. A leaf-dip assay was used to provide late 2nd instar larvae three feeding access periods: 24, 48, and 72 h, to evaluate the effect of gene silencing of each target. Larvae were fed tomato leaves coated with five different RNAi concentrations (10, 20, 30, 40, and 50 micrograms/centimeter-squared), that suppressed two genes (juvenile hormone protein, JHBP, and vacuolar-type adenosine triphosphatase enzyme, v-ATPase). Treatments with dsRNA showed a significant increase in mortality at 24, 48, and 72 h after ingestion (P < 0.01, α = 0.05), along with reduced leaf damage, and increased feeding deterrence. The results suggest that these two RNAi products may provide a suitable treatment for control of this and other lepidopteran pests.

The Regulatory Relationships Between the Gonad-Inhibiting Hormone and Insulin-Like Androgenic Gland Hormone-Binding Protein Genes in the Eyestalk-Androgenic Gland-Testis Axis of Macrobrachium rosenbergii

Gonad-inhibiting hormone (GIH) belongs to a family of neuropeptides that are released from the eyestalks of male crustaceans and plays key roles in gonadal maturity, reproduction, and molting. However, the detailed mechanisms underlying the effects of GIH on sexual regulation have yet to be elucidated. In the present study, we aimed to demonstrate how GIH mediate the activity of the androgenic gland (AG) to affect sexual regulation. To do this, we cloned and characterized a GIH sequence from Macrobrachium rosenbergii (MrGIH). The open reading frame (ORF) of MrGIH was 360 bp and codes for a polypeptide of 119 amino acids and a putative protein of 13.56 KDa. Tissue analysis showed that MrGIH is widely expressed in a range of tissues but particularly, the eyestalk, intestine, and nerve cord. Following the dsRNA silencing of MrGIH for 24 h, the expression levels of MrGIH were down-regulated in both the eyestalk and AG when compared with the negative control, but significantly increased the expression of Macrobrachium rosenbergii insulin-like androgenic gland hormone-binding protein (MrIAGBP) in AG, thus suggesting that MrGIH is an inhibitory factor for MrIAGBP. In addition, we found that eyestalk removal on certain days led to increased expression levels of MrIAGBP expression. The expression levels of MrIAGBP peaked at 2 d in the AG after unilateral and bilateral eyestalk ablation, exhibiting a 7.27- and 6.03-fold increase, respectively. Afterward, the expression of GIH protein levels were down-regulated and IAGBP protein levels were up-regulated after GIH silencing using immunohistochemistry method, combined with the increase of IAGBP protein levels after eyestalk ablation, confirming that MrGIH is an inhibitory factor that can moderately regulate AG development and IAGBP expression. Collectively, our findings enriched the mechanisms that control the sexual regulation pathway of male M. rosenbergii, and provided significant information for further explorations of the mechanism underlying sex regulation in other decapod crustaceans.

Development of A Recombinant Murine Luteinizing Hormone Binding Protein As A Selective Hormone Inhibitor

Physiological levels of luteinizing hormone (LH), in concert with follicle stimulating hormone (FSH), promote ovarian follicular development and ovulation. However, high LH levels associated with ovarian dysfunction have been shown to inhibit these processes. Thus, developing a selective LH inhibitor could be potentially useful for treating ovarian dysfunction. Here, we developed a mouse LH-binding protein (mLBP) composed of the extracellular domain of LH receptors as a selective inhibitor of mouse LH. After transient introduction of mLBP expressing vectors into Expi293F cells, mLBP was obtained as a soluble protein via a cleavage reaction with thrombin. The binding ability of mLBP for mouse LH was confirmed using sera containing high LH and FSH collected from ovariectomized (OVX) mice. The bioactivity of mLBP was demonstrated by inhibition of cAMP and testosterone productions induced by OVXmouse serum in mouse Leydig MLTC-1 cells expressing LH receptors. In contrast, mLBP did not bind mouse FSH and inhibit cAMP production induced by OVX-mouse serum in 293 cells expressing mouse FSH receptors. The mLBP also showed binding affinity to human LH (hLH), and inhibited hLH-induced cAMP production in MLTC-1 cells. Thus, the mLBP selectively suppresses the action of LH and is a potential therapeutic agent for ovarian dysfunction.

µ-Crystallin: A thyroid hormone binding protein

µ-Crystallin is a NADPH-regulated thyroid hormone binding protein encoded by the CRYM gene in humans. It is primarily expressed in the brain, muscle, prostate, and kidney, where it binds thyroid hormones, which regulate metabolism and thermogenesis. It also acts as a ketimine reductase in the lysine degradation pathway when it is not bound to thyroid hormone. Mutations in CRYM can result in non-syndromic deafness, while its aberrant expression, predominantly in the brain but also in other tissues, has been associated with psychiatric, neuromuscular, and inflammatory diseases. CRYM expression is highly variable in human skeletal muscle, with 15% of individuals expressing ≥13 fold more CRYM mRNA than the median level. Ablation of the Crym gene in murine models results in the hypertrophy of fast twitch muscle fibers and an increase in fat mass of mice fed a high fat diet. Overexpression of Crym in mice causes a shift in energy utilization away from glycolysis towards an increase in the catabolism of fat via β-oxidation, with commensurate changes of metabolically involved transcripts and proteins. The history, attributes, functions, and diseases associated with CRYM, an important modulator of metabolism, are reviewed.

Regulation of Juvenile Hormone on Summer Diapause of Geleruca daurica and Its Pathway Analysis

Juvenile hormone (JH) signaling plays an important role in regulation of reproductive diapause in insects. However, we have little understanding of the effect of JH on gene expression at the transcriptome level in diapause. Galeruca daurica is a new pest in the Inner Mongolia grasslands with obligatory summer diapause in the adult stage. Topical application of a JH analog methoprene at the pre-diapause stage delayed the adults entering diapause and inhibited lipid accumulation whereas it did not during diapause. Using Illumina sequencing technology and bioinformatics tools, 54 and 138 differentially expressed genes (DEGs) were detected at 1 and 2 d after treatment, respectively. The KEGG analysis showed that the DEGs were mainly enriched in the metabolism pathways. qRT-PCR analysis indicated that methoprene promoted the expression of genes encoding vitellogenin, fork head transcription factor and Krüppel homolog 1, whereas suppressed the expression of genes encoding juvenile hormone-binding protein, juvenile hormone esterase, juvenile hormone acid methyltransferase, juvenile hormone epoxide hydrolase and fatty acid synthase 2. These results indicate that JH signaling plays an important role in regulating reproductive diapause of G. daurica.

Anemia pada Sindrom Nefrotik Anak: Patogenesis dan Tata Laksana

Sindrom nefrotik merupakan penyakit ginjal yang sering pada anak, ditandai dengan proteinuria masif, hipo­albuminemia, edema, dan hiperkolesterolemia. Sindrom nefrotik dapat menyebabkan komplikasi hipovolemia, renjatan, gangguan ginjal akut, infeksi, tromboembolisme, gangguan elektrolit, gangguan endokrin, dan anemia. Komplikasi ini disebabkan hilangnya protein melalui urin, seperti albumin, faktor koagulasi, imunoglobulin, hormone-binding protein, transferin, dan eritropoietin. Anemia pada sindrom nefrotik dapat disebabkan perubahan homeostasis besi dan transferin, pengeluaran eritropoietin melalui urin, defisiensi vitamin B12, serta peran obat dan logam. Ekskresi besi dan transferin melalui urin menyebabkan kadar transferin plasma menurun yang mengakibatkan penurunan kadar besi plasma dan anemia mikrositik hipokrom. Kehilangan erItropoietin melalui urin menyebabkan anemia defisiensi eritropoietin. Kehilangan transkobalamin dan vitamin B12 melalui urin menurunkan kadar vitamin B12 plasma. Kehilangan seruloplasmin melalui urin dapat menyebabkan defisiensi tembaga yang mengakibatkan anemia. Obat angiotensin converting enzyme inhibitors (ACEIs) dapat menyebabkan anemia dengan mekanisme inhibisi eritropoiesis dengan menurunkan kadar eritropoietin sirkulasi. Keberhasilan terapi anemia pada sinrom nefrotik bergantung pada penyebab anemia. Anemia defisiensi besi diterapi dengan suplementasi besi. Pemberian eritropoietin rekombinan efektif dan aman dalam tata laksana anemia pada sindrom nefrotik. Defisiensi vitamin B12 diterapi dengan vitamin B12 dan anemia defisiensi tembaga diterapi dengan suplementasi tembaga glukonat.

Insight into the Regulatory Relationships between the Insulin-Like Androgenic Gland Hormone Gene and the Insulin-Like Androgenic Gland Hormone-binding Protein Gene in Giant Freshwater Prawns (Macrobrachium rosenbergii)

Giant freshwater prawns (Macrobrachium rosenbergii) are commonly found throughout the world. The size of the male giant freshwater prawn is much larger than that of the female. Therefore, understanding the molecular mechanism that underlies the sexual differentiation of M. rosenbergii is of both commercial and scientific importance. Insulin-like androgenic gland hormone (IAG) plays a key role in the differentiation of sex in M. rosenbergii. Although IAG has been investigated, the regulatory relationship between IAG and its binding protein partner, the insulin-like androgenic gland hormone-binding protein (IAGBP), has not been studied in M. rosenbergii. Here, we cloned and characterized the IAGBP from M. rosenbergii (Mr-IAGBP) for the very first time. Transcriptomic analysis showed that Mr-IAGBP mRNA was detected in a wide array of tissues with the highest expression found in the androgenic gland. The importance of IAG in male development was further demonstrated by an increase in IAG transcripts during the development of the androgenic gland and Mr-IAG was only highly transcribed in the androgenic gland of M. rosenbergii. Interestingly, we found that the Mr-IAG gene expression started during the 20th-day larva after hatching stage (LH20), followed (20th-day post-larval stage, PL20) by a gradual elevation of Mr-IAGBP levels. The levels of both genes peaked at the adult stage. The relationship between Mr-IAGBP and Mr-IAG was further analyzed using RNA interference. The injection of Mr-IAGBP double-stranded RNA (dsRNA) significantly reduced the transcription of Mr-IAG, while the amount of Mr-IAGBP mRNA and the translation of IAGBP protein was significantly reduced by the injection of Mr-IAG dsRNA. These results revealed that IAGBP is involved in IAG signaling. Furthermore, our data supports the hypothesis that (IAG and IAGBP)-IAG receptor signaling schemes exist in M. rosenbergii. Our results will provide important information for the further study of determining the sex of M. rosenbergii.