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Abstract Local tissue damage following snakebite envenoming remains a poorly researched area. To develop better strategies to treat snakebites, it is critical to understand the mechanisms through which venom toxins induce envenomation effects including local tissue damage. Here, we demonstrate how the venoms of two medically important Indian snakes (Russell's viper and cobra) affect human skeletal muscle using a cultured human myoblast cell line. The data suggest that both venoms affect the viability of myoblasts. Russell’s viper venom reduced the total number of cells, their migration, and the area of focal adhesions. It also suppressed myogenic differentiation and induced muscle atrophy. While cobra venom decreased the viability, it did not largely affect cell migration and focal adhesions. Cobra venom affected the formation of myotubes and induced atrophy. Cobra venom-induced atrophy could not be reversed by small molecule inhibitors such as varespladib (a phospholipase A2 inhibitor) and prinomastat (a metalloprotease inhibitor), and soluble activin type IIb receptor (a molecule used to promote regeneration of skeletal muscle), although the antivenom (raised against the Indian ‘Big Four’ snakes) has attenuated the effects. However, all these molecules rescued the myotubes from Russell’s viper venom-induced atrophy. This study demonstrates key steps in the muscle regeneration process that are affected by both Indian Russell’s viper and cobra venoms and offers insights into the potential causes of clinical features displayed in envenomed victims. Further research is required to investigate the molecular mechanisms of venom-induced myotoxicity under in vivo settings and develop better therapies for snakebite-induced muscle damage.

Abstract The human aryl hydrocarbon receptor (AHR) undergoes continuous shuttling between nucleus and cytoplasm. Binding to exogenous or endogenous ligands promotes its rapid nuclear import. The proposed mechanism for the ligand-dependent import is based on exposing the bipartite nuclear localisation signal (NLS) to members of the importin (IMP) superfamily. Among this, the molecular interactions involved in the basal import still need to be clarified. Utilizing fluorescently fused AHR variants, we recapitulated and characterized AHR localization and nucleo-cytoplasmic shuttling in living cells. Analysis of AHR variants carrying NLS point mutations demonstrated a mandatory role of first (13RKRRK17) and second (37KR-R40) NLS segments on the basal import of AHR. Further experiments indicated that ligand-induced import is mainly regulated through the first NLS, while the second NLS is supportive but not essential. Additionally, applying IMPα/β specific inhibitors, ivermectin (IVM) and importazole (IPZ), slowed down the ligand-induced import and, correspondingly, decreased the basal nuclear accumulation of the receptor. In conclusion, our data show that ligand-induced and basal nuclear entry of AHR rely on the same mechanism but are controlled uniquely by the two NLS components.

Abstract Networks are essential for analyzing complex systems. However, their growing size necessitates backbone extraction techniques aimed at reducing their size while retaining critical features. In practice, selecting, implementing, and evaluating the most suitable backbone extraction method may be challenging. This paper introduces netbone, a Python package designed for assessing the performance of backbone extraction techniques in weighted networks. Its comparison framework is the standout feature of netbone. Indeed, the tool incorporates state-of-the-art backbone extraction techniques. Furthermore, it provides a comprehensive suite of evaluation metrics allowing users to evaluate different backbones techniques. We illustrate the flexibility and effectiveness of netbone through the US air transportation network analysis. We compare the performance of different backbone extraction techniques using the evaluation metrics. We also show how users can integrate a new backbone extraction method into the comparison framework. netbone is publicly available as an open-source tool, ensuring its accessibility to researchers and practitioners. Promoting standardized evaluation practices contributes to the advancement of backbone extraction techniques and fosters reproducibility and comparability in research efforts. We anticipate that netbone will serve as a valuable resource for researchers and practitioners enabling them to make informed decisions when selecting backbone extraction techniques to gain insights into the structural and functional properties of complex systems.

Abstract Biochemical recurrence (BCR) of prostate cancer (PCa) occurs in about 25% of patients treated with radical prostatectomy (RP) and up to 45% in patients who receive external beam radiotherapy (RT). Early diagnosis of PCa recurrence is of high importance for successful salvage therapy. The aim of the present study is to analyze the efficacy of 68 Ga-PSMA PET/CT in detecting the presence of local and/or systemic disease in patients with a history of PCa who have BCR. A total of 52 PCa patients with BCR referred for 68 Ga-PSMA PET/CT were recruited from the American University of Beirut Medical Center between November 2017 and December 2019. We compared the performance of PSMA PET/CT to the results and clinical factors based on follow up: PSA, PSA kinetics, primary treatment, and Gleason score. The relationship between the PET/CT findings and clinical indicators of disease were assessed by univariate and multivariate logistic regression. From a total of 52 patients, 34 (65.4%) had positive PSMA-PET/CT scans. Among those, 8/34 (23.5%) received primary RT. For all patients with a positive PSMA-PET: the detection rate was 2/4 (50%) for PSA

Abstract The present study encompasses the application of cost effective, organo-modified bentonite material for efficient desulfurization of model oil and real fuel. For the adsorptive desulfurization of oil, dibenzothiophene (DBT) was used as model compound. Various experimental parameters (time, temperature, adsorbent-amount and DBT concentration) were thoroughly investigated. The synthesized material was characterized via X-ray diffraction (XRD), X-ray Fluorescence (XRF), Scanning electron microscopy (SEM), Energy dispersive x-ray (EDX), Thermogravimetric analysis (TGA) and Fourier transform infrared spectroscopy (FT-IR). The modification exhibits the increase in interlayer spacing of clay as confirmed from XRD and modified material shows interesting morphology as compared to unmodified bentonite. The results showed that > 90% of DBT removal was achieved under optimized conditions for B-BTC, B-BTB and B-DSS and > 80% for B-BEHA, for model fuel oil which are greater than unmodified clay (

Abstract The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. Binding to endogenous or xenobiotic ligands terminates the basal nucleo-cytoplasmic shuttling and stabilizes an exclusive nuclear population. The precise mechanisms that facilitate such stable nuclear accumulation remain to be clarified as essential step in the activation cascade. In this study, we have tested whether the sustained nuclear compartmentalization of ligand-bound or basal AHR might further require heterodimerization with the AHR-nuclear translocator (ARNT) and binding to the cognate XRE-motif. Mutagenesis of the DNA-binding motif or of selected individual residues in the ARNT-binding motif did not lead to any variation in AHR’s nucleo-cytoplasmic distribution. In response to ligands, all mutants were retained in the nucleus demonstrating that the stable compartmentalization of activated AHR in the nucleus is neither dependent on interactions with DNA, nor ARNT. Knocking down the ARNT gene using small interfering RNA confirmed that ARNT does not play any role in the intracellular trafficking of AHR.

Abstract Here we report a jute endophyte Staphylococcus hominis strain MBL_AB63 isolated from jute seeds which showed promising antimicrobial activity against Staphylococcus aureus SG511 when screening for antimicrobial substances. The whole genome sequence of this strain, annotated using BAGEL4 and antiSMASH 5.0 to predict the gene clusters for antimicrobial substances identified a novel antimicrobial peptide cluster that belongs to the class I lantibiotic group. The predicted lantibiotic (homicorcin) was found to be 82% similar to a reported peptide epicidin 280 having a difference of seven amino acids at several positions of the core peptide. Two distinct peaks obtained at close retention times from a RP-HPLC purified fraction have comparable antimicrobial activities and LC–MS revealed the molecular mass of these peaks to be 3046.5 and 3043.2 Da. The presence of an oxidoreductase (homO) similar to that of epicidin 280- associated eciO or epilancin 15X- associated elxO in the homicorcin gene cluster is predicted to be responsible for the reduction of the first dehydrated residue dehydroalanine (Dha) to 2-hydroxypropionate that causes an increase of 3 Da mass of homicorcin 1. Trypsin digestion of the core peptide and its variant followed by ESI–MS analysis suggests the presence of three ring structures, one in the N-terminal and other two interlocking rings at the C-terminal region that remain undigested. Homicorcin exerts bactericidal activity against susceptible cells by disrupting the integrity of the cytoplasmic membrane through pore formation as observed under FE-SEM.

Abstract This paper evaluates the forensic utility of 30 insertion-deletion polymorphism (indel) markers in a sample from the Bahraini population using the Qiagen Investigator DIPplex Kit. Allele frequencies and forensic stats of the 30 indels were investigated in 293 unrelated individuals from different governorates of the Kingdom of Bahrain. None of the markers showed significant deviation from Hardy Weinberg equilibrium except for HLD88 locus and no linkage disequilibrium were detected between all possible pair of the indel loci, assuming that these markers are independent and their allele frequencies can be used to calculate the match probabilities in the Bahraini population. The high power of discrimination (CPD = 0.9999999999998110) and the low combined match probability (CPM = 1.89 × 10−13) indicate that these markers are informative and can be successfully used for human identification in terms of forensics and paternity. Genetic distances and relatedness were displayed through multidimensional plotting and phylogenetic tree using various populations in the region. Our study showed that the Bahraini population was clustered with neighboring countries such as Kuwait and Emirates which indicates that these closely geographical regions share similar allele frequencies and are more genetically related than other reference population studied.

Abstract The highly successful PBE functional and the modified Becke–Johnson exchange potential were used to calculate the structural, electronic, and optical properties of the vacancy-ordered double perovskites A2BX6 (A = Rb, Cs; B = Sn, Pd, Pt; X = Cl, Br, and I) using the density functional theory, a first principles approach. The convex hull approach was used to check the thermodynamic stability of the compounds. The calculated parameters (lattice constants, band gap, and bond lengths) are in tune with the available experimental and theoretical results. The compounds, Rb2PdBr6 and Cs2PtI6, exhibit band gaps within the optimal range of 0.9–1.6 eV, required for the single-junction photovoltaic applications. The photovoltaic efficiency of the studied materials was assessed using the spectroscopic-limited-maximum-efficiency (SLME) metric as well as the optical properties. The ideal band gap, high dielectric constants, and optimum light absorption of these perovskites make them suitable for high performance single and multi-junction perovskite solar cells.

Abstract Meningioma is the most common primary intracranial extra-axial tumor. Total surgical removal is the standard therapeutic method to treat this type of brain tumors. However, the risk of recurrence depends on the tumor grade and the extent of the resection including the infiltrated dura mater and, if necessary, the infiltrated bone. Therefore, proper resection of all invasive tumor borders without touching eloquent areas is of primordial in order to decrease the risk of recurrence. Nowadays, none of the intraoperative used tools is able to provide a precise real-time histopathological information on the tumor surrounding areas to help the surgeon to achieve a gross total removal. To respond to this problem, our team is developing a multimodal two-photon fluorescence endomicroscope, compatible with the surgeon tool, to better delimitate tumor boundaries, relying on the endogenous fluorescence of brain tissues. In this context, we are building a tissue database in order to specify each brain tissue, whether healthy or tumoral, with its specific optical signature. In this study, we present a multimodal and multiscale optical measurements on non-tumoral control brain tissue obtained in epilepsy surgery patients and several meningioma grades. We investigated tissue auto-fluorescence to track the molecular changes associated with the tumor grade from deep ultra-violet (DUV) to near infrared (NIR) excitation. Micro-spectroscopy, fluorescence lifetime imaging, two-photon fluorescence imaging and Second Harmonic Generation (SHG) imaging were performed. Several optically derived parameters such as collagen crosslinks fluorescence in DUV, SHG emission in NIR and long lifetime intensity fraction of Nicotinamide Adenine Dinucleotide and Flavins were correlated to discriminate cancerous tissue from control one. While collagen response managed to discriminate meningioma grades from control samples with a 100% sensitivity and 90% specificity through a 3D discriminative algorithm.

Abstract This study evaluates the forensic utility of 23 autosomal short tandem repeat markers in 400 samples from the Kuwaiti population, of which four markers (D10S1248, D22S1045, D2S441 and SE33) are reported for the first time for Kuwait. All the markers were shown to exhibit no deviation from Hardy–Weinberg equilibrium, nor any linkage disequilibrium between and within loci, indicating that these loci are inherited independently, and their allele frequencies can be used to estimate match probabilities in the Kuwaiti population. The low combined match probability of 7.37 × 10–30 and the high paternity indices generated by these loci demonstrate the usefulness of the PowerPlex Fusion 6C kit for human identification in this population, as well as to strengthen the power of paternity testing. Off-ladder alleles were seen at several loci, and these were identified by examining their underlying nucleotide sequences. Principal component analysis (PCA) and STRUCTURE showed no genetic structure within the Kuwaiti population. However, PCA revealed a correlation between geographic and genetic distance. Finally, phylogenetic trees demonstrated a close relationship between Kuwaitis and Middle Easterners at a global level, and a recent common ancestry for Kuwait with its northern neighbours of Iraq and Iran, at a regional level.

Abstract The SIX1 homeobox gene belongs to the six homeodomain family and is widely thought to play a principal role in mediating of skeletal muscle development. In the present study, we determined that the bovine SIX1 gene was highly expressed in the longissimus thoracis and physiologically immature individuals. DNA sequencing of 428 individual Qinchuan cattle identified nine single nucleotide polymorphisms (SNPs) in the promoter region of the SIX1 gene. Using a series of 5′ deletion promoter plasmid luciferase reporter assays and 5′-rapid amplification of cDNA end analysis (RACE), two of these SNPs were found to be located in the proximal minimal promoter region −216/−28 relative to the transcriptional start site (TSS). Correlation analysis showed the combined haplotypes H1-H2 (-GG-GA-) was significantly greater in the body measurement traits (BMTs) than the others, which was consistent with the results showing that the transcriptional activity of Hap2 was higher than the others in Qinchuan cattle myoblast cells. Furthermore, the electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation assay (ChIP) demonstrated that NRF1 and ZSCAN10 binding occurred in the promoter region of diplotypes H1-H2 to regulate SIX1 transcriptional activity. This information may be useful for molecular marker-assisted selection (MAS) in cattle breeding.

Biochemical recurrence (BCR) of prostate cancer (PCa) occurs in about 25% of patients treated with radical prostatectomy (RP) and up to 45% in patients who receive external beam radiotherapy (RT). Early diagnosis of PCa recurrence is of high importance for successful salvage therapy. The aim of the present study is to analyze the efficacy of 68 Ga-PSMA PET/CT in detecting the presence of local and/or systemic disease in patients with a history of PCa who have BCR. A total of 52 PCa patients with BCR referred for 68 Ga-PSMA PET/CT were recruited from the American University of Beirut Medical Center between November 2017 and December 2019. We compared the performance of PSMA PET/CT to the results and clinical factors based on follow up: PSA, PSA kinetics, primary treatment, and Gleason score. The relationship between the PET/CT findings and clinical indicators of disease were assessed by univariate and multivariate logistic regression. From a total of 52 patients, 34 (65.4%) had positive PSMA-PET/CT scans. Among those, 8/34 (23.5%) received primary RT. For all patients with a positive PSMA-PET: the detection rate was 2/4 (50%) for PSA < 0.2, 5/10 (50%) for PSA 0.2–0.49, 3/6 (50%) for PSA 0.5–0.99, 6/12 (50%) for PSA 1–1.99, 8/9 (88.9%) for PSA 2–3.99, and 10/11 (90.9%) for PSA 4–10. PSMA-PET/CT positivity was significantly associated with PSA level at time of PET scan, PSA doubling time, Gleason score and TNM staging. However, it did not show a significant correlation with radiotherapy as primary treatment, ongoing androgen deprivation therapy (ADT), time to relapse, and initial PSA before therapy. In our single center prospective trial, 68 Ga-PSMA PET/CT successfully detected the recurrence of PCa in patients with BCR. Scan positivity was significantly associated with PSA level at time of PET scan, PSA doubling time, Gleason score, and TNM staging. PSMA- PET/CT is a highly promising modality in the work up of patients with PCa in the setting of BCR for earlier detection of disease recurrence. [ABSTRACT FROM AUTHOR]