Protein Prenylation in the moss Physcomitrium patens

Protein prenylation is the addition of a 15 or 20 carbon lipid to a cysteine near carboxyl terminus of target proteins. Prenylation increases hydrophobicity, which facilitates membrane associations and protein-protein interaction. Protein prenylation is generally conserved among eukaryotes, and mutations in genes that carry out prenylation are lethal in animals and yeast. In plants prenylation mutations are not always lethal, but they do affect development, disease resistance, biofuel production, and drought response, among other processes of agricultural interest. To understand the evolutionary and developmental implications of plant protein prenylation, we used the sequenced, annotated, and translated genome of the moss Physcomitrium patens to search for proteins that meet minimal criteria for prenylation; specifically the presence of a sequence that includes cysteine and one of six specific amino acids at the C terminus. We then analyzed these proteins with an online prenylation prediction program to assess their likelihood of being prenylated based on additional sequence motifs. We then determined potential biological function of putative target proteins by using BLAST sequence similarity searches to identify related genes with known function. We plan to use these data to select prenylated proteins with functions of interest for in vivo studies using genetic and molecular tools to investigate their roles in plant development and environmental response. REFERENCES http://www.jbc.org/cgi/doi/10.1074/jbc.M115.673491https://ir.library.louisville.edu/uars/1051/thumbnail.jp

Enhancing crop resilience by harnessing the synergistic effects of biostimulants against abiotic stress

Plants experience constant exposed to diverse abiotic stresses throughout their growth and development stages. Given the burgeoning world population, abiotic stresses pose significant challenges to food and nutritional security. These stresses are complex and influenced by both genetic networks and environmental factors, often resulting in significant crop losses, which can reach as high as fifty percent. To mitigate the effects of abiotic stresses on crops, various strategies rooted in crop improvement and genomics are being explored. In particular, the utilization of biostimulants, including bio-based compounds derived from plants and beneficial microbes, has garnered considerable attention. Biostimulants offer the potential to reduce reliance on artificial chemical agents while enhancing nutritional efficiency and promoting plant growth under abiotic stress condition. Commonly used biostimulants, which are friendly to ecology and human health, encompass inorganic substances (e.g., zinc oxide and silicon) and natural substances (e.g., seaweed extracts, humic substances, chitosan, exudates, and microbes). Notably, prioritizing environmentally friendly biostimulants is crucial to prevent issues such as soil degradation, air and water pollution. In recent years, several studies have explored the biological role of biostimulants in plant production, focusing particularly on their mechanisms of effectiveness in horticulture. In this context, we conducted a comprehensive review of the existing scientific literature to analyze the current status and future research directions concerning the use of various biostimulants, such as plant-based zinc oxide, silicon, selenium and aminobutyric acid, seaweed extracts, humic acids, and chitosan for enhancing abiotic stress tolerance in crop plants. Furthermore, we correlated the molecular modifications induced by these biostimulants with different physiological pathways and assessed their impact on plant performance in response to abiotic stresses, which can provide valuable insights

Development of new TAK-285 derivatives as potent EGFR/HER2 inhibitors possessing antiproliferative effects against 22RV1 and PC3 prostate carcinoma cell lines

AbstractEpidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) protein tyrosine kinases co-expressed in various cancers such as ovarian, breast, colon, and prostate subtypes. Herein, new TAK-285 derivatives (9a–h) were synthesised, characterised, and biologically evaluated as dual EGFR/HER2 inhibitors. Compound 9f exhibited IC50 values of 2.3 nM over EGFR and 234 nM over HER2, which is 38-fold of staurosporine and 10-fold of TAK-285 over EGFR. Compound 9f also showed high selectivity profile when tested over a small kinase panel. Compounds 9a–h showed IC50 values in the range of 1.0–7.3 nM and 0.8–2.8 nM against PC3 and 22RV1 prostate carcinoma cell lines, respectively. Cell cycle analysis, apoptotic induction, molecular docking, dynamics, and MM-GBSA studies confirmed the plausible mechanism(s) of compound 9f as a potent EGFR/HER2 dual inhibitor with an effective antiproliferative action against prostate carcinoma

IgG1 as a potential biomarker of post-chemotherapeutic relapse in visceral leishmaniasis, and adaptation to a rapid diagnostic test.

BACKGROUND: Visceral leishmaniasis (VL), caused by protozoa of the Leishmania donovani complex, is a widespread parasitic disease of great public health importance; without effective chemotherapy symptomatic VL is usually fatal. Distinction of asymptomatic carriage from progressive disease and the prediction of relapse following treatment are hampered by the lack of prognostic biomarkers for use at point of care. METHODOLOGY/PRINCIPAL FINDINGS: All IgG subclass and IgG isotype antibody levels were determined using unpaired serum samples from Indian and Sudanese patients with differing clinical status of VL, which included pre-treatment active VL, post-treatment cured, post-treatment relapsed, and post kala-azar dermal leishmaniasis (PKDL), as well as seropositive (DAT and/or rK39) endemic healthy controls (EHCs) and seronegative EHCs. L. donovani antigen-specific IgG1 levels were significantly elevated in relapsed versus cured VL patients (p<0.0001). Using paired Indian VL sera, consistent with the known IgG1 half-life, IgG1 levels had not decreased significantly at day 30 after the start of treatment (p = 0.8304), but were dramatically decreased by 6 months compared to day 0 (p = 0.0032) or day 15 (p<0.0001) after start of treatment. Similarly, Sudanese sera taken soon after treatment did not show a significant change in the IgG1 levels (p = 0.3939). Two prototype lateral flow immunochromatographic rapid diagnostic tests (RDTs) were developed to detect IgG1 levels following VL treatment: more than 80% of the relapsed VL patients were IgG1 positive; at least 80% of the cured VL patients were IgG1 negative (p<0.0001). CONCLUSIONS/SIGNIFICANCE: Six months after treatment of active VL, elevated levels of specific IgG1 were associated with treatment failure and relapse, whereas no IgG1 or low levels were detected in cured VL patients. A lateral flow RDT was successfully developed to detect anti-Leishmania IgG1 as a potential biomarker of post-chemotherapeutic relapse

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially