N-WASP is competent for downstream signaling before full release from autoinhibition.

Allosteric regulation of intrinsically disordered proteins (IDPs) is still vastly understudied compared to the counterpart of structured proteins. Here, we used molecular dynamics simulations to characterize the regulation of the IDP N-WASP by the binding of its basic region with inter- and intramolecular ligands (PIP2 and an acidic motif, respectively). The intramolecular interactions keep N-WASP in an autoinhibited state; PIP2 binding frees the acidic motif for interacting with Arp2/3 and thereby initiating actin polymerization. We show that PIP2 and the acidic motif compete in binding with the basic region. However, even when PIP2 is present at 30% in the membrane, the acidic motif is free of contact with the basic region ("open" state) in only 8.5% of the population. The very C-terminal three residues of the A motif are crucial for Arp2/3 binding; conformations where only the A tail is free are present at a much higher population than the open state (40- to 6-fold, depending on the PIP2 level). Thus, N-WASP is competent for Arp2/3 binding before it is fully freed from autoinhibition.

Potential soil organic carbon sequestration vis-a-vis methane emission in lowland rice agroecosystem.

Mitigating the atmospheric greenhouse effect while enhancing the inherent soil quality and productive capacity is possible through soil carbon (C) sequestration, which has a significant potential to counteract the adverse effects of agroecosystem level C emission through natural and anthropogenic means. Although rice is the most important food in India, feeding more than 60% of the country's population, it is commonly blamed for significant methane (CH4) emissions that accelerate climate change. Higher initial soil organic matter concentrations would create more CH4 under the flooded soil conditions, as reducible soil C is a prerequisite for CH4 generation. In India, rice is generally cultivated in lowlands under continuous flooding. Less extensive organic matter breakdown in lowland rice agroecosystems often significantly impacts the dynamics of soil active and passive C pools. Change from conventional to conservation agriculture might trap a significant quantity of SOC. The study aims to investigate the potential of rice-based soils to sequester C and reduce the accelerated greenhouse effects through modified farming practices, such as crop residue retention, crop rotation, organic farming, varietal selection, conservation agriculture, integrated nutrient management, and water management. Overall, lowland rice agroecosystems can sequester significant amounts of SOC, but this potential must be balanced against the potential for CH4 emissions. Management practices that reduce CH4 emissions while increasing soil C sequestration should be promoted and adopted to maximize the sustainability of rice agroecosystems. This review is important for understanding the effectiveness of the balance between SOC sequestration and CH4 emissions in lowland rice agroecosystems for adopting sustainable agricultural practices in the context of climate change.

Roles of glycogen synthase kinase 3 alpha and calcineurin in regulating the ability of sperm to fertilize eggs.

Glycogen synthase kinase 3 (GSK3) was identified as an enzyme regulating sperm protein phosphatase. The GSK3α paralog, but not GSK3ß, is essential for sperm function. Sperm lacking GSK3α display altered motility and are unable to undergo hyperactivation, which is essential for fertilization. Male mice lacking sperm-specific calcineurin (PP2B), a calcium regulated phosphatase, in testis and sperm, are also infertile. Loss of PP2B results in impaired epididymal sperm maturation and motility. The phenotypes of GSK3α and PP2B knockout mice are similar, prompting us to examine the interrelationship between these two enzymes in sperm. High calcium levels must exist to permit catalytically active calcineurin to function during epididymal sperm maturation. Total and free calcium levels are high in immotile compared to motile epididymal sperm. Inhibition of calcineurin by FK506 results in an increase in the net phosphorylation and a consequent decrease in catalytic activity of sperm GSK3. The inhibitor FK506 and an isoform-selective inhibitor of GSK3α, BRD0705, also inhibited fertilization of eggs in vitro. Interrelated functions of GSK3α and sperm PP2B are essential during epididymal sperm maturation and during fertilization. Our results should enable the development of male contraceptives targeting one or both enzymes.

Systemic Immune-Inflammation Index Predicts Poor Outcome After Elective Off-Pump CABG: A Retrospective, Single-Center Study.

OBJECTIVES: To investigate the role of preoperative hematologic indices (neutrophil-lymphocyte ratio [NLR], platelet-lymphocyte ratio [PLR], systemic immune-inflammation index [SII; neutrophil × platelet/lymphocyte) in predicting short-term outcomes after off-pump coronary artery bypass grafting (OPCABG). DESIGN: A single-center, retrospective, risk-prediction study. SETTING: A tertiary cardiac center. PARTICIPANTS: 1,007 patients undergoing elective OPCABG. INTERVENTIONS: No specific intervention. MEASUREMENTS AND MAIN RESULTS: Two hundred five patients out of 1,007 (20.4%) manifested poor postoperative outcome (defined by ≥1 of: major adverse cardiac and cardiovascular events, duration of mechanical ventilation (DO-MV) >24 hours, new-onset renal failure, sepsis, and death). On univariate analysis, age, diabetes mellitus (DM), European System for Cardiac Operative Risk Evaluation II (EuroSCORE II), left-main disease, recent myocardial infarction, poor left ventricular ejection fraction, hemoglobin, NLR, PLR, and SII significantly predicted poor outcome. However, DM, EuroSCORE II, and SII emerged as independent predictors on multivariate analysis (odds ratio 0.136; 0.035-0.521, 3.377; 95% confidence interval 2.373-4.806, 1.01, 1.003-1.016). The SII cutoff of 878.06 × 103/mm3 predicted poor outcome with 97.6% sensitivity, 91%, specificity, and area under the curve 0.984. There was a significant positive correlation between the SII values and DO-MV and length of intensive care unit stay (R = 0.676; 0.527, p < 0.001). The incidence of complications, such as atrial fibrillation, intra-aortic balloon pump requirement, vasoactive-ionotropic score >20 for >6 hours, and other infections, was also significantly higher in patients with SII ≥878.06 × 103/mm3. CONCLUSIONS: SII constitutes a parsimonious and reproducible parameter demonstrating the potential of delineating the patients vulnerable to poor outcomes after OPCABG given the combined contribution of pro-inflammatory and pro-thrombotic corpuscular lines in computing the novel index.

Cyclic AMP and glycogen synthase kinase 3 form a regulatory loop in spermatozoa.

The multifaceted glycogen synthase kinase (GSK3) has an essential role in sperm and male fertility. Since cyclic AMP (cAMP) plays an important role in sperm function, we investigated whether GSK3 and cAMP pathways may be interrelated. We used GSK3 and soluble adenylyl cyclase (sAC) knockout mice and pharmacological modulators to examine this relationship. Intracellular cAMP levels were found to be significantly lower in sperm lacking GSK3α or GSK3ß. A similar outcome was observed when sperm cells were treated with SB216763, a GSK3 inhibitor. This reduction of cAMP levels was not due to an effect on sperm adenylyl cyclase but was caused by elevated phosphodiesterase (PDE) activity. The PDE4 inhibitor RS25344 or the general PDE inhibitor IBMX could restore cAMP levels in sperm lacking GSK3α or ß-isoform. PDE activity assay also showed that hyperactivated PDE4 contributes in lowering of cAMP levels in GSK3α null sperm suggesting that in wild-type sperm PDE4 activity is kept in check by GSK3. Conversely, PKA being triggered by cAMP, affected GSK3 activity through increasing its phosphorylation. Increased GSK3 phosphorylation also occurred by inhibition of sperm specific protein phosphatase type 1, PP1γ2. The relationship between cAMP, GSK3, and PP1γ2 activities was also confirmed in sperm from sAC null mice. Pull-down assay using recombinant PP1γ2 indicated that PKA, GSK3, and PP1γ2 could exist as a complex. Pharmacological inhibition of GSK3 in mature spermatozoa resulted in significantly reduced fertilization of eggs in vitro. Our results show that cAMP, PKA, and GSK3 are interrelated in regulation of sperm function.

Isoform-specific requirement for GSK3α in sperm for male fertility.

Glycogen synthase kinase 3 (GSK3) is a highly conserved protein kinase regulating key cellular functions. Its two isoforms, GSK3α and GSK3ß, are encoded by distinct genes. In most tissues the two isoforms are functionally interchangeable, except in the developing embryo where GSK3ß is essential. One functional allele of either of the two isoforms is sufficient to maintain normal tissue functions. Both GSK3 isoforms, present in sperm from several species including human, are suggested to play a role in epididymal initiation of sperm motility. Using genetic approaches, we have tested requirement for each of the two GSK3 isoforms in testis and sperm. Both GSK3 isoforms are expressed at high levels during the onset of spermatogenesis. Conditional knockout of GSK3α, but not GSK3ß, in developing testicular germ cells in mice results in male infertility. Mice lacking one allele each of GSK3α and GSK3ß are fertile. Despite overlapping expression and localization in differentiating spermatids, GSK3ß does not substitute for GSK3α. Loss of GSK3α impairs sperm hexokinase activity resulting in low ATP levels. Net adenine nucleotide levels in caudal sperm lacking GSK3α resemble immature caput epididymal sperm. Changes in the association of the protein phosphatase PP1γ2 with its protein interactors occurring during epididymal sperm maturation is impaired in sperm lacking GSK3α. The isoform-specific requirement for GSK3α is likely due to its specific binding partners in the sperm principal piece. Testis and sperm are unique in their specific requirement of GSK3α for normal function and male fertility.

Radiosensitization by the PARP inhibitor olaparib in BRCA1-proficient and deficient high-grade serous ovarian carcinomas.

OBJECTIVE: Approximately 15-25% of high-grade serous ovarian carcinomas (HGSOC) harbor BRCA1/2 mutations. Inhibition of Poly (ADP-ribose) polymerase (PARP) is synthetically lethal to cells and tumors with BRCA1/2 mutation. Our goal was to investigate the radiosensitizing effects of PARP inhibitor olaparib in HGSOC with different BRCA1 status. METHODS: The radiosensitizing effects of olaparib were tested on BRCA1-proficient and deficient HGSOC by clonogenic survival and tumor growth assays. The effects of olaparib and radiation on DNA damage, PARP activity, and apoptosis were determined. RESULTS: BRCA1-deficient HGSOC cells were more sensitive to RT alone and exhibited significantly higher levels of olaparib-mediated radiosensitization compared to BRCA1-proficient cells. Furthermore, when combined with RT, olaparib inhibited DNA damage repair and PARP1 activity, increased apoptosis, decreased growth of HGSOC xenografts and increased overall host survival. The growth-inhibitory effects of the combined olaparib and RT treatment were more pronounced in mice bearing BRCA1-deficient tumors compared to BRCA1-proficient tumors. CONCLUSIONS: These results provide a preclinical rationale for improved treatment modalities using olaparib as an effective radiosensitizer in HGSOC, particularly in tumors with BRCA1-deficiencies.

Can an ammonium-based room temperature ionic liquid counteract the urea-induced denaturation of a small peptide?

The folding/unfolding equilibrium of proteins in aqueous medium can be altered by adding small organic molecules generally termed as co-solvents. Denaturants such as urea are instrumental in the unfolding of proteins while protecting osmolytes favour the folded ensemble. Recently, room temperature ionic liquids (ILs) have been shown to counteract the deleterious effect of urea on proteins. In this paper, using atomistic molecular dynamics we show that a ternary mixture containing a particular ammonium-based IL, triethylammonium acetate (TEAA), and urea (in 1 : 5 molar ratio) helps a small 15-residue S-peptide analogue regain most of its native structure, whereas a binary aqueous mixture containing a large amount of urea alone completely distorts it. Our simulations show that the denaturant urea directly interacts with the peptide backbone in the binary mixture while for the ternary mixture both urea as well as the IL are preferentially excluded from the peptide surface.

Crystal structures of GCN2 protein kinase C-terminal domains suggest regulatory differences in yeast and mammals.

In response to amino acid starvation, GCN2 phosphorylation of eIF2 leads to repression of general translation and initiation of gene reprogramming that facilitates adaptation to nutrient stress. GCN2 is a multidomain protein with key regulatory domains that directly monitor uncharged tRNAs which accumulate during nutrient limitation, leading to activation of this eIF2 kinase and translational control. A critical feature of regulation of this stress response kinase is its C-terminal domain (CTD). Here, we present high resolution crystal structures of murine and yeast CTDs, which guide a functional analysis of the mammalian GCN2. Despite low sequence identity, both yeast and mammalian CTDs share a core subunit structure and an unusual interdigitated dimeric form, albeit with significant differences. Disruption of the dimeric form of murine CTD led to loss of translational control by GCN2, suggesting that dimerization is critical for function as is true for yeast GCN2. However, although both CTDs bind single- and double-stranded RNA, murine GCN2 does not appear to stably associate with the ribosome, whereas yeast GCN2 does. This finding suggests that there are key regulatory differences between yeast and mammalian CTDs, which is consistent with structural differences.

Role of epididymal anti sticking factor in sperm capacitation.

Sperm capacitation depends on several features like hormones, ions, intracellular signaling, sperm associated molecules, etc. Anti sticking factor (ASF) is a novel sperm surface associated glycoprotein isolated from epididymal plasma. Function of ASF in vivo has not been revealed yet. The current study is an attempt to highlight the surface localization of ASF and corresponding biochemical changes that occurs in sperm cells during in vitro capacitation. In the presence of 1 nM ASF, percentage of bicarbonate and BSA induced capacitated cells in modified Tyrode medium (7.2) decreased from 72.45% to 16.25% as per Merocyanine 540 (M540)/DAPI stained flowcytometric analysis. Indirect immunocytostaining and western blot analysis shows that the amount of sperm surface bound residual ASF decline during in vitro capacitation. ASF at its effective concentrations notably reduced the bicarbonate and BSA induced cholesterol efflux. These data help in concluding ASF as a majorly responsible molecule that maintains caprine sperm membrane integrity by inhibiting cholesterol efflux. As the capacitation process, progress at in vitro condition, ASF is found to be released from the sperm surface and cell moved from non-capacitated to the capacitated state.

Role of forward-motility-stimulating factor as an extracellular activator of soluble adenylyl cyclase.

Forward-motility-stimulating factor (FMSF) is a protein, originally purified from bubaline serum, that promotes progressive motility of mature spermatozoa. FMSF binds to sperm surface receptors and activates transmembrane adenylyl cyclase (tmAC), causing a rise in intracellular cyclic AMP level ([cAMP]i) and subsequent activation of a protein kinase A/tyrosine kinase-mediated pathway that enhances forward motility. This article further evaluates how FMSF works in the caprine system, particularly identifying the stimulatory effect of this glycoprotein on soluble adenylyl cyclase (sAC). Elevated [cAMP]i, initially resulting from FMSF-dependent activation of tmAC, was associated with the release of Ca(2+) from an intracellular calcium store in the sperm head, likely via an inositol triphosphate-sensitive calcium ion channel. This peak Ca(2+) concentration of ∼125-175 nM was capable of stimulating sAC in vitro in a calmodulin-independent manner, thereby triggering more cAMP production. Our model proposes that a positive-feedback loop mediated by cAMP and Ca(2+) is established in FMSF-stimulated sperm, with cAMP playing the role of a chemical messenger at multiple steps, resulting in the observed progressive motility. Thus, FSMF stimulates a novel signaling cascade that synergistically activate both tmAC and sAC to achieve forward sperm motility.

Receptor expression is essential for forward motility in the course of sperm cell maturation.

Forward motility stimulating factor (FMSF) is a glycoprotein previously purified from buffalo blood serum that promotes progressive motility of caprine caudal spermatozoa. We have prepared a functionally active covalent conjugate of this factor with horseradish-peroxidase (HRP) to obtain an idea of its binding efficacy on maturing spermatozoa. Receptor-assay was performed using FMSF-HRP conjugate in saturating conditions to bind with spermatozoa isolated from different epididymal segments. Activity and binding profile of the motility stimulating factor coincided, suggesting both these parameters come into play only partially when spermatozoa reach the maturation state in the distal-corpus region and largely in caudal part (around 24% and 80% binding and 10% and 79% forward motility, respectively). Spermatozoa from caput up to mid-corpus regions neither displayed any substantial binding with FMSF nor exhibited significant induction in forward motility. Study of cell surface-bound FMSF on maturing spermatozoa in physiological milieu demonstrated their presence on anterior spermhead and suggests a nearly similar pattern of occurrence. Flow-cytometric analysis also implies analogous presence of this receptor. The factor was also immunodetected in uterine fluids of cattle species. This study displays a maturation-dependent expression of FMSF-receptor and consequential stimulation of forward motility that may be crucial for its journey to meet the ovum.

Occurrence of novel Cu(2+)-dependent sialic acid-specific lectin, on the outer surface of mature caprine spermatozoa.

Effects of several bivalent metal ions on the autoagglutination event in mature caprine epididymal sperm cells have been investigated using a chemically defined medium. This study demonstrates for the first time that Copper (Cu(2+)) ion (300 µM) has high specificity for autoagglutination of mature cauda-epididymal sperm. Head-to-head interaction of the male gametes is responsible for this event. Studies on the effect of various sugars reveal that the autoagglutinated cells can be dissociated specifically with neutralized sialic acid (50 mM), which also inhibits the sperm cell autoagglutination phenomenon. Blood serum protein fetuin, that contains terminal sialic acid residue, showed high efficacy for inhibiting this autoagglutination event at 4 µM concentration. However, asialofetuin is not capable of inhibiting this Cu(2+)-dependent cellular event. Mature sperm cells bound with caprine erythrocytes at their head region in presence of Cu(2+) ion. The purified sperm membrane fraction isolated by aqueous two phase polymer method showed high efficacy to agglutinate erythrocytes. These sperm-erythrocyte interactions as well as sperm membrane induced haemagglutination were strongly blocked by neutralized sialic acid (50 mM). The results confirm the occurrence of unique Cu(2+) dependent, sialic acid-specific lectin on the outer surface of a mammalian cell using caprine sperm as the model. The observed Cu(2+)-mediated cellular autoagglutination is caused by the interaction of the cell surface lectin with the lectin receptor on the surface of the neighboring homologous cell.

Role of Alpha-Fetoprotein in the Pathogenesis of Cancer.

Alpha-fetoprotein (AFP) belongs to the albuminoid protein family and is considered as the fetal analog of serum albumin. This plasma protein is initially synthesized in the fetal liver and yolk sac and shows a maximum peak near the end of the first trimester. Later, concentrations begin to decline prenatally and drop precipitously after birth. This protein has three key ligand-binding pockets for interactions with various biomolecules. It contains multiple phosphorylation and acetylation sites for the regulation of physiological and pathophysiological states. High serum AFP titer is an established biomarker for yolk sac, embryonal and hepatocellular carcinoma. The present review critically analyzes the chemical nature, receptors, clinical implications, and therapeutic aspects of AFP, underpinning the development of different types of cancer.

Transcriptional repression of ATF4 gene by CCAAT/enhancer-binding protein ß (C/EBPß) differentially regulates integrated stress response.

Different environmental stresses induce the phosphorylation of eIF2 (eIF2∼P), repressing global protein synthesis coincident with preferential translation of ATF4. ATF4 is a transcriptional activator of genes involved in metabolism and nutrient uptake, antioxidation, and regulation of apoptosis. Because ATF4 is a common downstream target that integrates signaling from different eIF2 kinases and their respective stress signals, the eIF2∼P/ATF4 pathway is collectively referred to as the integrated stress response. Although eIF2∼P elicits translational control in response to many different stresses, there are selected stresses, such as exposure to UV irradiation, that do not increase ATF4 expression despite robust eIF2∼P. The rationale for this discordant induction of ATF4 expression and eIF2∼P in response to UV irradiation is that transcription of ATF4 is repressed, and therefore ATF4 mRNA is not available for preferential translation. In this study, we show that C/EBPß is a transcriptional repressor of ATF4 during UV stress. C/EBPß binds to critical elements in the ATF4 promoter, resulting in its transcriptional repression. Expression of C/EBPß increases in response to UV stress, and the liver-enriched inhibitory protein (LIP) isoform of C/EBPß, but not the liver-enriched activating protein (LAP) version, represses ATF4 transcription. Loss of the liver-enriched inhibitory protein isoform results in increased ATF4 mRNA levels in response to UV irradiation and subsequent recovery of ATF4 translation, leading to enhanced expression of its target genes. Together these results illustrate how eIF2∼P and translational control combined with transcription factors regulated by alternative signaling pathways can direct programs of gene expression that are specifically tailored to each environmental stress.

Why Does Synergistic Activation of WASP, but Not N-WASP, by Cdc42 and PIP2 Require Cdc42 Prenylation?

Human WASP and N-WASP are homologous proteins that require the binding of multiple regulators, including the acidic lipid PIP2 and the small GTPase Cdc42, to relieve autoinhibition before they can stimulate the initiation of actin polymerization. Autoinhibition involves intramolecular binding of the C-terminal acidic and central motifs to an upstream basic region and GTPase binding domain. Little is known about how a single intrinsically disordered protein, WASP or N-WASP, binds multiple regulators to achieve full activation. Here we used molecular dynamics simulations to characterize the binding of WASP and N-WASP with PIP2 and Cdc42. In the absence of Cdc42, both WASP and N-WASP strongly associate with PIP2-containing membranes, through their basic region and also possibly through a tail portion of the N-terminal WH1 domain. The basic region also participates in Cdc42 binding, especially for WASP; consequently Cdc42 binding significantly compromises the ability of the basic region in WASP, but not N-WASP, to bind PIP2. PIP2 binding to the WASP basic region is restored only when Cdc42 is prenylated at the C-terminus and tethered to the membrane. This distinction in the activation of WASP and N-WASP may contribute to their different functional roles.

Revisiting the gonadotropic regulation of mammalian spermatogenesis: evolving lessons during the past decade.

Spermatogenesis is a multi-step process of male germ cell (Gc) division and differentiation which occurs in the seminiferous tubules of the testes under the regulation of gonadotropins - Follicle Stimulating Hormone (FSH) and Luteinising hormone (LH). It is a highly coordinated event regulated by the surrounding somatic testicular cells such as the Sertoli cells (Sc), Leydig cells (Lc), and Peritubular myoid cells (PTc). FSH targets Sc and supports the expansion and differentiation of pre-meiotic Gc, whereas, LH operates via Lc to produce Testosterone (T), the testicular androgen. T acts on all somatic cells e.g.- Lc, PTc and Sc, and promotes the blood-testis barrier (BTB) formation, completion of Gc meiosis, and spermiation. Studies with hypophysectomised or chemically ablated animal models and hypogonadal (hpg) mice supplemented with gonadotropins to genetically manipulated mouse models have revealed the selective and synergistic role(s) of hormones in regulating male fertility. We here have briefly summarized the present concept of hormonal control of spermatogenesis in rodents and primates. We also have highlighted some of the key critical questions yet to be answered in the field of male reproductive health which might have potential implications for infertility and contraceptive research in the future.

IDO1 and inflammatory neovascularization: bringing new blood to tumor-promoting inflammation.

In parallel with the genetic and epigenetic changes that accumulate in tumor cells, chronic tumor-promoting inflammation establishes a local microenvironment that fosters the development of malignancy. While knowledge of the specific factors that distinguish tumor-promoting from non-tumor-promoting inflammation remains inchoate, nevertheless, as highlighted in this series on the 'Hallmarks of Cancer', it is clear that tumor-promoting inflammation is essential to neoplasia and metastatic progression making identification of specific factors critical. Studies of immunometabolism and inflamometabolism have revealed a role for the tryptophan catabolizing enzyme IDO1 as a core element in tumor-promoting inflammation. At one level, IDO1 expression promotes immune tolerance to tumor antigens, thereby helping tumors evade adaptive immune control. Additionally, recent findings indicate that IDO1 also promotes tumor neovascularization by subverting local innate immunity. This newly recognized function for IDO1 is mediated by a unique myeloid cell population termed IDVCs (IDO1-dependent vascularizing cells). Initially identified in metastatic lesions, IDVCs may exert broader effects on pathologic neovascularization in various disease settings. Mechanistically, induction of IDO1 expression in IDVCs by the inflammatory cytokine IFNγ blocks the antagonistic effect of IFNγ on neovascularization by stimulating the expression of IL6, a powerful pro-angiogenic cytokine. By contributing to vascular access, this newly ascribed function for IDO1 aligns with its involvement in other cancer hallmark functionalities, (tumor-promoting inflammation, immune escape, altered cellular metabolism, metastasis), which may stem from an underlying role in normal physiological functions such as wound healing and pregnancy. Understanding the nuances of how IDO1 involvement in these cancer hallmark functionalities varies between different tumor settings will be crucial to the future development of successful IDO1-directed therapies.

Atrial Fibrillation and Perioperative Inflammation (FIBRILLAMMED Study): A Retrospective Analysis of the Predictive Role of Preoperative Albumin-Adjusted Platelet-Leukocytic Indices in OPCABG.

Objective: New-onset atrial fibrillation (NOAF), an important postoperative complication, has pertinent inflammatory links. Motivated by the encouraging literature on the prognostic role of hypoalbuminemia, leukocytic indices [LIs: neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR)], systemic inflammation response index (SIRI=NLR×monocyte) and platelet-leukocytic indices [PLIs: platelet-to-lymphocyte ratio (PLR)], systemic immune inflammation index (SII=NLR×platelet), aggregate index of systemic inflammation (AISI=NLR×platelet×monocyte), we sought to investigate the NOAF-predictive value of preoperative albumin-adjusted indices (aa-LIs and aa-PLIs) in an off-pump coronary artery bypass grafting (OPCABG) setting. Methods: Of 899 patients, 151 patients (16.79%) developed the primary outcome i.e. NOAF that was analyzed further retrospectively for its predictors instead of the highlighted text perioperative data of 899 patients undergoing elective OPCABG, were retrospectively analyzed. The study participants were categorized into non-NOAF and NOAF groups (defined as new-onset atrial arrhythmia with irregular RR interval with indistinct P wave in the first week postoperatively). Results: One hundred and fifty-one patients (16.79%) developed NOAF. On univariate analysis: age, smoker status, The European System for Cardiac Operative Risk Evaluation (EuroSCORE) II, systemic hypertension, diabetes mellitus, prior congestive heart failure (CHF), and a higher preoperative NLR, PLR, SII, and albumin were significant predictors of NOAF. While age, CHF, and EuroSCORE II retained predictive significance in multivariate analysis, LI-PLIs and albumin did not emerge as independent NOAF predictors. Notably, aa-NLR, aa-PLR, and aa-SII independently predicted NOAF on the computation of model-estimates in the regression analysis (Odds ratio; 95% confidence interval: 31.05;15.75-70.61, 1.04;1.02-1.05, 1.12;1.10-1.14, respectively, P < 0.001). aa-NLR ≥1.32, aa-PLR ≥52.64, and aa-SII ≥344.38 predicted NOAF with the respective AUC;sensitivity;specificity of 0.66;63.6%;73.3%, 0.63;66.2%;59.0%, and 0.65;58.3%;78.2%. Preoperative aa-NLR, aa-PLR and aa-SII also positively correlated with CHA2DS2-VASc score (R=0.40, 0.45 and 0.42; P < 0.001). Conclusion: The independent NOAF predictive value of aa-NLR, aa-PLR, and aa-SII reiterates the inflammatory relationship of the arrhythmic complication following OPCABG.