Nitric oxide: A potential etiological agent for vaso-occlusive crises in sickle cell disease.

Nitric oxide (NO), a vasodilator contributes to the vaso-occlusive crisis associated with the sickle cell disease (SCD). Vascular nitric oxide helps in vasodilation, controlled platelet aggregation, and preventing adhesion of sickled red blood cells to the endothelium. It decreases the expression of pro-inflammatory genes responsible for atherogenesis associated with SCD. Haemolysis and activated endothelium in SCD patients reduce the bioavailability of NO which promotes the severity of sickle cell disease mainly causes vaso-occlusive crises. Additionally, NO depletion can also contribute to the formation of thrombus, which can cause serious complications such as stroke, pulmonary embolism etc. Understanding the multifaceted role of NO provides valuable insights into its therapeutic potential for managing SCD and preventing associated complications. Various clinical trials and studies suggested the importance of artificially induced nitric oxide and its supplements in the reduction of severity. Further research on the mechanisms of NO depletion in SCD is needed to develop more effective treatment strategies and improve the management of this debilitating disease.

A cell line derived from heart of rainbow trout is refractory to Tilapia lake virus.

Cell lines are important in vitro models to answer biological mechanisms with less genetic variations. The present study was attempted to develop a cell line from rainbow trout, where we obtained a cell line from the heart, named "RBT-H." The cell line was authenticated using karyotyping and cytochrome c oxidase subunit I (COI) gene sequencing. The karyotype demonstrated diploid chromosome number (2n) as 62 and the sequence of partial COI gene was 99.84% similar to rainbow trout COI data set, both suggesting the origin of RBT-H from the rainbow trout. The heart cell line was mycoplasma-free and found to be refractory to infection with the Tilapia lake virus. The RBT-H cell line is deposited in the National Repository of Fish Cell Line (NRFC) at ICAR-NBFGR, Lucknow, India, with Accession no. NRFC0075 for maintenance and distribution to researchers on request for R&D.

Interferon inducible guanylate-binding protein 1 modulates the lipopolysaccharide-induced cytokines/chemokines and mitogen-activated protein kinases in macrophages.

Guanylate-binding proteins (GBPs) are a family of interferon (IFN)-inducible GTPases and play a pivotal role in the host immune response to microbial infections. These are upregulated in immune cells after recognizing the lipopolysaccharides (LPS), the major membrane component of Gram-negative bacteria. In the present study, the expression pattern of GBP1-7 was initially mapped in phorbol 12-myristate 13-acetate-differentiated human monocytes THP-1 and mouse macrophages RAW 264.7 cell lines stimulated with LPS. A time-dependent significant expression of GBP1-7 was observed in these cells. Moreover, among the various GBPs, GBP1 has emerged as a central player in regulating innate immunity and inflammation. Therefore, to study the specific role of GBP1 in LPS-induced inflammation, knockdown of the Gbp1 gene was carried out in both cells using small interfering RNA interference. Altered levels of different cytokines (interleukin [IL]-4, IL-10, IL-12ß, IFN-γ, tumor necrosis factor-α), inducible nitric oxide synthase, histocompatibility 2, class II antigen A, protein kinase R, and chemokines (chemokine (C-X-C motif) ligand 9 [CXCL9], CXCL10, and CXCL11) in GBP1 knockdown cells were reported compared to control cells. Interestingly, the extracellular-signal-regulated kinase 1/2 mitogen-activated protein (MAP) kinases and signal transducer and activator of transcription 1 (STAT1) transcription factor levels were considerably induced in knockdown cells compared to the control cells. However, no change in the level of phosphorylated nuclear factor-kB, c-Jun, and p38 transcription factors was observed in GBP1 knockdown cells compared to the control cells. This study concludes that GBP1 may alter the expression of cytokines, chemokines, and effector molecules mediated by MAP kinases and STAT1 transcription factors.

Xylooligosaccharides from lignocellulosic biomass and their applications as nutraceuticals: a review on their production, purification, and characterization.

Xylooligosaccharides (XOS) are considered a potent source of prebiotics for humans. The global prebiotic market is expanding in size, was valued at USD 6.05 billion in 2021, and is expected to grow at a 14.9% compound annual growth rate between 2022 and 2030, indicating a huge demand. These XOS are non-digestible pentose sugar oligomers comprising mainly xylose. Xylose is naturally present in the lignocellulosic biomass (LCB), fruits and vegetables. Apart from the prebiotic effect, these XOS have been reported to reduce blood cholesterol, possess antioxidant effects, increase calcium absorption, reduce colon cancer risk, and benefit diabetic patients. The primary use of XOS is reported in the feed industry followed by health, medical use, food and drinks. LCB mainly contains glucan, xylan and lignin. After glucan, xylan is the second-highest available sugar on the globe composed of xylose. Therefore, the xylan fraction of LCB has great significance in producing food, feed and energy. Glucan has been exploited for the commercial production of ethanol, xylitol, furfural, hydroxymethyl furfural and glucose. As of now, xylan has limited applications. Therefore, xylan can be exploited to convert to XOS. The production of XOS from LCB fraction not only helps to produce these at a very low price, but also helps in the reduction of greenhouse gases. Its use in food and drinks is increasing as it can be derived from the abundantly and cheaply available LCB. The article provides a review on the production, purification and characterization of XOS in view of their use as nutraceuticals. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

In-Depth Comparison of Genetic Variants Demonstrates a Close Relationship Between Invasive and Intraductal Components of Prostate Cancer.

Intraductal carcinoma (IDC) of the prostate is often associated with concurrent high-grade invasive prostate cancer (PCa) and poor clinical outcomes. In this context, IDC is thought to represent the retrograde spread of invasive prostatic adenocarcinoma into the acini and ducts. Prior studies have demonstrated a concordance of PTEN loss and genomic instability between the IDC and high-grade invasive components of PCa, but larger genomic association studies to solidify our understanding of the relationship between these 2 lesions are lacking. Here, we evaluate the genomic relationship between duct-confined (high-grade prostatic intraepithelial neoplasia and IDC) and invasive components of high-grade PCa using genetic variants generated by whole exome sequencing. High-grade prostatic intraepithelial neoplasia and IDC were laser-microdissected, and PCa and nonneoplastic tissue was manually dissected from 12 radical prostatectomies. A targeted next-generation sequencing panel was used to identify disease-relevant variants. Additionally, the degree of overlap between adjacent lesions was determined by comparing exome-wide variants detected using whole exome sequencing data. Our results demonstrate that IDC and invasive high-grade PCa components show common genetic variants and copy number alterations. Hierarchical clustering of genome-wide variants suggests that in these tumors, IDC is more closely related to the high-grade invasive components of the tumor compared with high-grade prostatic intraepithelial neoplasia. In conclusion, this study reinforces the concept that, in the context of high-grade PCa, IDC likely represents a late event associated with tumor progression.

TPWshiny: an interactive R/Shiny app to explore cell line transcriptional responses to anti-cancer drugs.

SUMMARY: The NCI Transcriptional Pharmacodynamics Workbench (NCI TPW) is an extensive compilation of directly measured transcriptional responses to anti-cancer agents across the well-characterized NCI-60 cancer cell lines. The NCI TPW data are publicly available through a web interface that allows limited user interaction with the data. We developed 'TPWshiny' as a standalone, easy to install, R application to facilitate more interactive data exploration.With no programming skills required, TPWshiny provides an intuitive and comprehensive graphical interface to help researchers understand the response of tumor cell lines to 15 therapeutic agents. The data are presented in interactive scatter plots, heatmaps, time series and Venn diagrams. Data can be queried by drug concentration, time point, gene and tissue type. Researchers can download the data for further analysis. AVAILABILITY AND IMPLEMENTATION: Users can download the ready-to-use, self-extracting package for Windows or macOS, and R source code from the project website (https://brb.nci.nih.gov/TPWshiny/). TPWshiny documentation and additional information can be found on the project website.

One-pot C-C, C-N, and C-S bond construction for synthesis of 3-sulfenylindoles directly from unactivated anilines involving dual palladium catalysis and mechanistic insights from DFT.

An efficient dual Pd-catalytic system was developed for one-pot synthesis of 3-sulfenylindoles via C-C, C-N and C-S bond construction directly from unactivated 2-iodo(NH)anilines under mild reaction conditions. Furthermore, 3-selenyl/halo/carbon-functionalized indoles were synthesized in good yields and a short reaction time. The synthetic utility of 3-sulfenylindole was also demonstrated. The key role of solvent in palladium catalysis was unravelled by DFT.

Transferrin decorated PLGA encumbered moxifloxacin nanoparticles and in vitro cellular studies.

PURPOSE: Complicated intra-abdominal infection (cIAI) management involves administering antibiotics that destroy the cell wall and the genesis of bacterial lipopolysaccharide (LPS). During the infectious state, the expression of transferrin receptors upregulates on the intestinal epithelial cells, which are considered the site of infection. In the present research, transferrin decorated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) encapsulated moxifloxacin (MOX) were developed for possible targeting of the receptors in the colon. SIGNIFICANCE: This study will explore more about the incorporation of transferrin as effective coating material in targeted drug delivery. METHODS: Nanoparticles were prepared using nano-emulsification and surface modification with transferrin was done by layer-by-layer methodology and evaluated by powder X-ray diffraction (PXRD), differential scanning calorimeter (DSC), FTIR, SEM, antibacterial activity, and cellular uptake studies. RESULTS: The formulated NPs exhibit a size of ≈170 nm, PDI ≈ 0.25, zeta potential ≈-4.0 mV, drug loading ≈ 6.8%, and entrapment efficiency of 82%. Transferrin-decorated NPs exhibit tailored release for almost 12 h and in vitro antibacterial activity for 14 h. The cellular uptake studies were done on a RAW264.7 cell line for better determination of transferrin uptake of fabricated NPs. CONCLUSION: The above study circumvents around the preparation of transferrin decorated PLGA encumbered MOX NPs intended for cIAI-induced sepsis. PLGA NPs provide tailored release of MOX with primary burst and followed by sustained release. These observations confines with antibacterial activity studies. The prepared transferrin-coated NPs were stable and effectively uptaken by RAW264.7 cells. However, future studies include the preclinical investigation of these NPs in sepsis-induced murine models.

Interferon inducible guanylate binding protein 1 restricts the growth of Leishmania donovani by modulating the level of cytokines/chemokines and MAP kinases.

Visceral Leishmaniasis (VL) is a zoonotic chronic endemic infectious disease caused by Leishmania donovani infection and a well-studied model for intracellular parasitism. Guanylate binding proteins (GBPs) are induced by interferons (IFNs), and play a crucial role in cell autonomous immunity and the regulation of inflammation. Guanylate-binding protein 1 (GBP1) has been shown vital for the host immune response against various pathogens. However, the role of GBP1 during VL is undefined. In the present study, we have investigated the role of GBP1 in Leishmania donovani infection using in vitro model. For that, knock down of the Gbp1 gene was carried out in both PMA differentiated human monocyte cell line THP-1 and mouse macrophages RAW264.7 cell line using siRNA based RNA interference. Infection of these cell lines revealed a high parasite load in knock down cells at 24 and 48h post infection as compared to control cells. A significant increase was observed in the level of different cytokines (IL-4, IL-10, IL-12b, IFN-γ, TNF-α) and chemokines (CXCL9, CXCL 10, and CXCL 11) in GBP1 knock down cell lines after post-infection. In GBP1 knock down cells the expression level of IFN effector molecules (iNOS and PKR) was found to be elevated in THP1 cells and remained almost unchanged in RAW264.7 cells after Leishmania donovani infection as compared to the control cells. Moreover, interestingly, the level of MAPK activated ERK1/2, and p38 MAPK were considerably induced by the parasite in knock down cells as compared to control after 24 h post-infection. This study, first time reported the involvement of GBP1 in Leishmania donovani infection by modulating the level of important cytokines, chemokines, IFN effector molecules, and MAP kinases.

Sustainable C-H activation approach for palladium-catalyzed, regioselective functionalization of 1-methyl-3-phenyl quinoxaline-2(1H)-ones in water.

A sustainable and environment-friendly approach for the regioselective acylation of 1-methyl-3-phenyl quinoxaline-2(1H)-ones has been developed in water. The present protocol requires palladium acetate as a catalyst and exhibits a wide substrate scope by employing commercially available, non-toxic aldehydes, benzyl alcohols and toluenes as acyl surrogates. The mechanistic studies demonstrated the adoption of a free radical pathway for this transformation. Furthermore, the established protocol exhibits excellent regioselectivity and high functional group tolerance and is amenable to the gram scale. The established synthetic method also provides a practical and convenient route for the late-stage functionalization of some potential drug candidates.

mRNALoc: a novel machine-learning based in-silico tool to predict mRNA subcellular localization.

Recent evidences suggest that the localization of mRNAs near the subcellular compartment of the translated proteins is a more robust cellular tool, which optimizes protein expression, post-transcriptionally. Retention of mRNA in the nucleus can regulate the amount of protein translated from each mRNA, thus allowing a tight temporal regulation of translation or buffering of protein levels from bursty transcription. Besides, mRNA localization performs a variety of additional roles like long-distance signaling, facilitating assembly of protein complexes and coordination of developmental processes. Here, we describe a novel machine-learning based tool, mRNALoc, to predict five sub-cellular locations of eukaryotic mRNAs using cDNA/mRNA sequences. During five fold cross-validations, the maximum overall accuracy was 65.19, 75.36, 67.10, 99.70 and 73.59% for the extracellular region, endoplasmic reticulum, cytoplasm, mitochondria, and nucleus, respectively. Assessment on independent datasets revealed the prediction accuracies of 58.10, 69.23, 64.55, 96.88 and 69.35% for extracellular region, endoplasmic reticulum, cytoplasm, mitochondria, and nucleus, respectively. The corresponding values of AUC were 0.76, 0.75, 0.70, 0.98 and 0.74 for the extracellular region, endoplasmic reticulum, cytoplasm, mitochondria, and nucleus, respectively. The mRNALoc standalone software and web-server are freely available for academic use under GNU GPL at http://proteininformatics.org/mkumar/mrnaloc.

Structural characterization of an activin class ternary receptor complex reveals a third paradigm for receptor specificity.

TGFß family ligands, which include the TGFßs, BMPs, and activins, signal by forming a ternary complex with type I and type II receptors. For TGFßs and BMPs, structures of ternary complexes have revealed differences in receptor assembly. However, structural information for how activins assemble a ternary receptor complex is lacking. We report the structure of an activin class member, GDF11, in complex with the type II receptor ActRIIB and the type I receptor Alk5. The structure reveals that receptor positioning is similar to the BMP class, with no interreceptor contacts; however, the type I receptor interactions are shifted toward the ligand fingertips and away from the dimer interface. Mutational analysis shows that ligand type I specificity is derived from differences in the fingertips of the ligands that interact with an extended loop specific to Alk4 and Alk5. The study also reveals differences for how TGFß and GDF11 bind to the same type I receptor, Alk5. For GDF11, additional contacts at the fingertip region substitute for the interreceptor interactions that are seen for TGFß, indicating that Alk5 binding to GDF11 is more dependent on direct contacts. In support, we show that a single residue of Alk5 (Phe84), when mutated, abolishes GDF11 signaling, but has little impact on TGFß signaling. The structure of GDF11/ActRIIB/Alk5 shows that, across the TGFß family, different mechanisms regulate type I receptor binding and specificity, providing a molecular explanation for how the activin class accommodates low-affinity type I interactions without the requirement of cooperative receptor interactions.

BAC-FISH Based Physical Map of Endangered Catfish Clarias magur for Chromosome Cataloguing and Gene Isolation through Positional Cloning.

Construction of a physical chromosome map of a species is important for positional cloning, targeted marker development, fine mapping of genes, selection of candidate genes for molecular breeding, as well as understanding the genome organization. The genomic libraries in the form of bacterial artificial chromosome (BAC) clones are also a very useful resource for physical mapping and identification and isolation of full-length genes and the related cis acting elements. Some BAC-FISH based studies reported in the past were gene based physical chromosome maps of Clarias magur (magur) to understand the genome organization of the species and to establish the relationships with other species in respect to genes' organization and evolution in the past. In the present study, we generated end sequences of the BAC clones and analyzed those end sequences within the scaffolds of the draft genome of magur to identify and map the genes bioinformatically for each clone. A total of 36 clones mostly possessing genes were identified and used in probe construction and their subsequent hybridization on the metaphase chromosomes of magur. This study successfully mapped all 36 specific clones on 16 chromosome pairs, out of 25 pairs of magur chromosomes. These clones are now recognized as chromosome-specific makers, which are an aid in individual chromosome identification and fine assembly of the genome sequence, and will ultimately help in developing anchored genes' map on the chromosomes of C. magur for understanding their organization, inheritance of important fishery traits and evolution of magur with respect to channel catfish, zebrafish and other species.

Evaluation of Paper-Based Point of Care Screening Test for Sickle Cell Disease.

The aim of the study is to evaluate the stability and longevity of the paper-based screening test for the sickle cell disease in relation to different temperatures and storage time. Blood stain patterns were interpreted after spotting the blood-buffer mixture (phosphate buffer, saponin and sodium metabisulfite) on chromatographic paper (Whatman no. 3). The stability of the buffer was tested after keeping the buffer at different temperature for 24 h. Longevity of the buffer was tested post storage for various time intervals. Test indicated reproducibility with the buffer stored at 4°C. The 15% metabisulfite buffer was found to be stable up to 180 days at 4°C and showed accurate identification of all genotypes. The tests revealed 100% sensitivity and 100% specificity in identification of HbS. However, the sensitivity of differentiation between sickle cell trait (AS) with disease (SS) was found to be 97.7% with 100% specificity. The paper-based screening test may be used as a method of choice for the screening of sickle cell anemia in community-based screening programs. The low-cost, rapid, and accurate point of care testing tools offer an avenue for effective screening in developing nations.

Krüppel-like factor 1 (KLF1) gene single nucleotide polymorphisms in sickle cell disease and its association with disease-related morbidities.

Sickle cell disease has varied clinical symptoms, and patients having high fetal hemoglobin (HbF) have milder symptoms. Various genetic factors are known to modulate the HbF levels. Krüppel-like factor 1 (KLF1) is a transcription factor that regulates the beta-like globin gene expression. Any variation in KLF1 gene may alter the sickle cell disease phenotype. Xmn-I polymorphism is also known to regulate the gamma globin gene expression. Present studies were carried out to investigate the effect of KLF1 gene mutations and Xmn-I polymorphism on the sickle cell disease severity and to ascertain the genotype-phenotype correlation. One hundred and eighteen sickle cell disease patients having a median follow-up of 5 years (3-10 years) were recruited. Clinical details were recorded from their retrospective medical records. Xmn-I polymorphism were analyzed using PCR-RFLP method. Variations in KLF1 gene were identified using Sanger sequencing. Out of 118 patients, 24 had acute chest syndrome and 21 patients had more than 2 pain episodes per year. There were no significant differences in sickle cell disease-related morbidities in male and females barring leg ulcers. A total of 6 polymorphism were observed in KLF1 gene, out of which 3 are novel (c.-304G > C, c.*141A > G and c.*178A > G). No statistically significant association of any of SNPs identified in KLF1 gene or Xmn-I polymorphism was seen with HbF levels as well as the sickle cell disease-related morbidities. No association exists between fetal hemoglobin or sickle cell disease-related morbidities and Xmn-I polymorphism or with SNPs identified in KLF1 gene in the studied cohort.

Semen quality and total microbial load: An association study in important Indian Goat breeds during different seasons.

The invasion of the male urogenital tract by microorganisms, and its subsequent effects on sperm fertilising ability, has not been well discussed in bucks. The present study was conducted to assess the bacterial load in fresh semen of the 2-6 years old bucks. For conducting the experiment, semen ejaculates from 18 bucks (6 from each breed namely Jakhrana, Jamunapari and Barbari) were used. We collected 5 ejaculates from each buck in each season (Summer-April to June, Rainy-July to Sept and Winter-November to January). Semen was collected with the artificial vagina (AV) method, and separate AV was used for each buck every time. The semen collection frequency was once in a week. Immediately after initial evaluation, collected semen samples were transferred to the microbiology laboratory of the institute. Thereafter, the semen samples were subjected to bacteriological examination to assess the microbial load. The results of the current study indicate that the microbial load in the semen was significantly (p < 0.05) higher in the Jamunapari bucks and in aged bucks. Bacteriospermia in different seasons was not significantly varied; however, nonsignificant increase in microbial load during the rainy season was observed. Overall, the average bacterial load in the semen of Jamunapari, Barbari and Jakhrana bucks was found 540.50 ± 55.88 CFU/ml, 391.81 ± 46.33CFU/ml and 388.93 ± 44.71 CFU/ml respectively. No significant difference in bacterial counts in the subsequent ejaculates among bucks was observed. Moreover, correlation analysis revealed that the proportions of motility, viability, plasma membrane integrity and acrosomal integrity were negatively influenced by the increased bacterial contamination of buck semen.

Isolation and characterization of hypoxia inducible heme oxygenase 1 (HMOX1) gene in Labeo rohita.

The HMOX1 gene plays role in several biological processes and is also responsive to hypoxia stress. Freshwater carp fish, Labeo rohita, is reported as hypoxia sensitive, but the information of annotated hypoxia genes in public domain is very scanty for this species. Here, an attempt was made to isolate and characterize HMOX1 gene in L. rohita using information from zebrafish. HMOX1 gene was obtained by mapping HMOX1 protein of zebrafish over assembled genome of L. rohita. Aligned region was used for designing primers for HMOX1 amplification. Eight overlapping sets of primers were designed for amplifying ~540 bp long successive overlapping fragments. Splicing of overlapping amplicons generated 3715 bp fragment that was confirmed as HMOX1 gene having full coding region with 6 exons between 184 and 2156 bp positions. HMOX1 characterization is an initiative for L. rohita genes annotation to support the characterization of new genes in the important species.

Determination of cut-off of diagnostic ELISA for Scrub typhus in endemic setup: Central India.

Serology remains the mainstay for diagnosis of scrub typhus. In central India, diagnosis of this neglected emerging zoonotic disease suffers due to lack of standardized region-specific cutoff value and diagnostic test. Henceforth, standardized region-specific cutoff value for diagnostic ELISA play a significant role in initial treatment of patients and to differentiate other febrile diseases in endemic setup. A total of 144 patients of all age groups with acute undifferentiated febrile illness patients, forty healthy controls, dengue and chikungunya positive thirty-five samples in each category, respectively were enrolled in the study and subjected to IgM ELISA (InBioS, International, Inc.). Samples showing OD value more than 0.5 in IgM ELISA, were subjected to nested PCR. Both, receiver operating characteristic (ROC) curve and healthy volunteer samples mean with +3 SD were considered to generate region specific cutoff OD value. A total of 48 patients were diagnosed as cases of scrub typhus through IgM ELISA. Out of 48 samples, 30 were positive by nested PCR. The ROC curve analysis revealed a diagnostic ELISA cutoff value of 0.73 with sensitivity and specificity of 95% and 100%, respectively. The cut off arrived from healthy volunteer is mean OD + 3 SD is 0.72. Considering the significance of scrub typhus diagnosis for treatment and to understand disease dynamics in region wise, the cutoff value of >0.72 for diagnostic ELISA for Madhya Pradesh in central India can be used.

Smad2/3-pathway ligand trap luspatercept enhances erythroid differentiation in murine ß-thalassaemia by increasing GATA-1 availability.

In ß-thalassaemia, anaemia results from ineffective erythropoiesis characterized by inhibition of late-stage erythroid differentiation. We earlier used luspatercept and RAP-536 protein traps for certain Smad2/3-pathway ligands to implicate Smad2/3-pathway overactivation in dysregulated erythroid differentiation associated with murine ß-thalassaemia and myelodysplasia. Importantly, luspatercept alleviates anaemia and has been shown to reduce transfusion burden in patients with ß-thalassaemia or myelodysplasia. Here, we investigated the molecular mechanisms underlying luspatercept action and pSmad2/3-mediated inhibition of erythroid differentiation. In murine erythroleukemic (MEL) cells in vitro, ligand-mediated overactivation of the Smad2/3 pathway reduced nuclear levels of GATA-1 (GATA-binding factor-1) and its transcriptional activator TIF1γ (transcription intermediary factor 1γ), increased levels of reactive oxygen species, reduced cell viability and haemoglobin levels, and inhibited erythroid differentiation. Co-treatment with luspatercept in MEL cells partially or completely restored each of these. In ß-thalassaemic mice, RAP-536 up-regulated Gata1 and its target gene signature in erythroid precursors determined by transcriptional profiling and gene set enrichment analysis, restored nuclear levels of GATA-1 in erythroid precursors, and nuclear distribution of TIF1γ in erythroblasts. Bone marrow cells from ß-thalassaemic mice treated with luspatercept also exhibited restored nuclear availability of GATA-1 ex vivo. Our results implicate GATA-1, and likely TIF1γ, as key mediators of luspatercept/RAP-536 action in alleviating ineffective erythropoiesis.

Identifying residues that determine palmitoylation using association rule mining.

MOTIVATION: In eukaryotes, palmitoylation drives several essential cellular mechanisms like protein sorting, protein stability and protein-protein interaction. Several amino acids namely Cys, Gly, Ser, Thr and Lys undergo palmitoylation. But very little is known about the amino acid patterns that promote palmitoylation. RESULTS: We deduced presence of statistically significant amino acids around palmitoylation sites and their association with different palmitoylated residues i.e. Cys, Gly and Ser. The results suggest that palmitoylation, irrespective of its target residue, generally occurs at sites where Cys, Leu, Lys, Arg, Ser and Met are abundant. Furthermore, functional properties of the three types of palmitoylated proteins were compared. We observed similar functional behavior of Cys and Gly palmitoylated proteins but proteins with Ser palmitoylation showed distinctiveness from remaining two. Motif-wise functional conservation was also observed in Cys palmitoylated proteins. We also did functional annotation of predicted human palmitoylome. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.