Minor Region Research Articles

Electrochemical quantification based on the interactions of nucleoside analog cladribine with dsDNA via experimental and in-silico studies

Cladribine is a deoxyadenosine analog prodrug originally developed to treat hairy-cell leukemia and other lymphoproliferative diseases. However, it is now primarily used in the treatment of relapsing types of multiple sclerosis (MS). Understanding how medications interact with dsDNA is crucial for developing more effective and efficient medications. This study aims to examine the binding behavior of cladribine with dsDNA via various analytical methods, such as heat denaturation, UV spectroscopy, fluorescence spectroscopy, electrochemistry, and viscosity tests. The binding constant (Kb) of cladribine with dsDNA has been estimated to be 2.41 × 104 ± 0.20 at 298 K using the Benesi-Hildebrand plot. Molecular docking simulations were employed to explore the dsDNA-cladribine interactions quantitatively at the molecular level. Molecular Dynamic simulations were performed to follow the stability of drug-bound DNA for 50 ns. The simulations revealed that cladribine binds to dsDNA via the minor groove region of DNA by forming hydrogen bonds mainly with Guanine's DNA bases. The post-MD analyses enabled us to follow the stability of DNA and cladribine complex. Additionally, two methods based on the electrochemical approach were developed in this study for low-level cladribine assessment using differential pulse voltammetry (DPV). The first method relies on cladribine oxidation in pH 2 phosphate buffer, while the second method uses deoxyguanosine oxidation signals resulting from cladribine and dsDNA binding in pH 4.80 acetate buffer. The analytical efficacy of the two methods was verified using cladribine concentrations ranging from 2 to 25 μM, with a limit of detection (LOD) of 0.30 and 0.92 μM, respectively. Furthermore, the study conducted percent recovery tests by employing pharmaceutical injection using both established methodologies.

Physical geographic regions in the Gulf of California defined using unsupervised learning algorithms

The Gulf of California (GOC) is a semi-enclosed sea off northwestern Mexico. It is considered one of the ten biodiversity hotspots of the world and sustains important fisheries at different scales. Unsupervised learning algorithms, particularly clustering techniques, can extract groups or clusters from the raw data; they do not require labelling the data a-priori, thus eliminating the subjectivity when assigning labels manually (i.e., supervised algorithms). In our study, we used a multivariate dataset of physical variables (Sea Surface Temperature, Salinity, Mixed Layer Depth, Sea Surface Height, and the U, V components of the geostrophic surface currents; 0.25° spatial resolution and monthly temporal resolution) and a hierarchical clustering algorithm to define physical regions in the GOC. We also defined minor, intermediate and major regions based on a quantile criterion. Our results indicate that 22 different regions exist in the GOC: eight minor, six intermediate, and eight major. More than one physical region was defined in every previously defined region, suggesting that the surface dynamics of the GOC are more complex than previously described.

Integrated eQTL mapping approach reveals genomic regions regulating candidate genes of the E8-r3 locus in soybean.

Deciphering the gene regulatory networks of critical quantitative trait loci associated with early maturity provides information for breeders to unlock soybean's (Glycine max (L.) Merr.) northern potential and expand its cultivation range. The E8-r3 locus is a genomic region regulating the number of days to maturity under constant short-day photoperiodic conditions in two early-maturing soybean populations (QS15524F2:F3 and QS15544RIL) belonging to maturity groups MG00 and MG000. In this study, we developed a combinatorial expression quantitative trait loci mapping approach using three algorithms (ICIM, IM, and GCIM) to identify the regions that regulate three candidate genes of the E8-r3 locus (Glyma.04G167900/GmLHCA4a, Glyma.04G166300/GmPRR1a, and Glyma.04G159300/GmMDE04). Using this approach, a total of 2,218 trans (2,061 genes)/7 cis (7 genes) and 4,073 trans (2,842 genes)/3,083 cis (2,418 genes) interactions were mapped in the QS15524F2:F3 and QS15544RIL populations, respectively. From these interactions, we successfully identified two hotspots (F2_GM15:49,385,092-49,442,237 and F2_GM18:1,434,182-1,935,386) and three minor regions (RIL_GM04:17,227,512-20,251,662, RIL_GM04:31,408,946-31,525,671 and RIL_GM13:37,289,785-38,620,690) regulating the candidate genes of E8-r3 and several of their homologs. Based on co-expression network and single nucleotide variant analyses, we identified ALTERED PHLOEM DEVELOPMENT (Glyma.15G263700) and DOMAIN-CONTAINING PROTEIN 21 (Glyma.18G025600) as the best candidates for the F2_GM15:49,385,092-49,442,237 and F2_GM18:1,434,182-1,935,386 hotspots. These findings demonstrate that a few key regions are involved in the regulation of the E8-r3 candidates GmLHCA4a, GmPRR1a, and GmMDE04.

Temporal and spatial variation in subsurface cryosphere in East Coprates Planum, Mars

There is general acceptance among researchers regarding the presence of a cryosphere in the subsurface of Mars. The two main geomorphic indications assumed to support the existence of this cryospheric layer are layered ejecta rampart craters and outflow channels. In essence, a layered ejecta rampart crater is a crater with an ejecta blanket having an asymmetric lobate geometry surrounding it. While there are no outflow channels in the East Coprates Planum, which is located within Mars’ equatorial region, it does have a population of layered ejecta rampart craters. Therefore, these craters are the only avenues to study the local cryospheric level at the time of impacts which likely led to their formation. Identification, mapping and dating of Single Layered Ejecta craters (SLE) and Multiple Layered Ejecta craters (MLE), the two types of layered ejecta rampart crater present in East Coprates Planum, was integral to this study. Excavation depths (with respect to the areoid) and ages for each crater was estimated. Statistical surfaces for SLE and MLE craters were drawn to assess the control of local topography on the local cryosphere. It has been estimated, by comparing excavation depths of SLEs and MLE with respect to their time of formation, that the bottom layer of the Martian cryosphere in the study area was at lower altitudes (from areoid) prior to ∼2.65 Ga, than it was in ∼0.97 Ga. This indicates a change in the Martian cryosphere over time within the study region, and the analysis of the crater excavation depths indicates that the cryosphere became thinner over time. Also, East Coprates Planum being a lower elevated region may have facilitated a greater inflow of groundwater from surrounding regions as compared to the adjacent higher elevated Thaumasia Minor region.

SIR epidemics in interconnected networks: threshold curve and phase transition

For simplicity of mathematical modeling of epidemic spreading, the assumption is that hosts have identical rates of disease-causing contacts. However, in the real world, the scenario is different. The network-based framework allows us to capture the complex interdependencies and structural heterogeneity present in real-world systems. We examine two distinct scenarios involving the dynamics of susceptible-infected-recovered (SIR) in interconnected networks. In the first part, we show how the epidemic threshold of a contact network changes as a result of being coupled with another network for a fixed infection strength. The model employed in this work considers both the contact networks and interconnections as generic. We have depicted the epidemic threshold curve for interconnected networks, considering the assumption that the infection could be initially present in either one or both of the networks. If the normalized infection strengths are above the threshold curve, the infection spreads, whereas if the normalized infection strengths are below the threshold curve, the disease does not spread. This is true for any level of interconnection. In the second part, we investigate the spillover phenomenon, where the disease in a novel host population network comes from a reservoir network. We have observed a clear phase transition when the number of links or the inter-network infection rate exceeds a certain threshold, keeping all other parameters constant. We observe two regimes for spillover: a major spillover region and a minor spillover region based on interpopulation links (fraction of links between two networks) and inter-network infection strength (infection rate between reservoir and host network). If the interpopulation links and inter-network infection strength are in the major spillover region, the spillover probability is high, while if the former parameters are in the minor spillover region, the spillover probability is low. When the number of infected individuals within a reservoir network is nearly equal, and the inter-network infection strength remains constant, the threshold number of links required to achieve the spillover threshold condition varies based on the network topology. Overall, this work contributes to the understanding of SIR dynamics in interconnected networks and sheds light on the behavior of epidemics in complex systems.

Non-linear machine learning coupled near infrared spectroscopy enhanced model performance and insights for coffee origin traceability

Over the past decade, there has been overwhelming interest in rapid and routine origin tracing and authentication methods, such as near infrared (NIR) spectroscopy. In a systematic and comprehensive approach, this study coupled NIR with advanced machine learning models to explore the origin classification of coffee at various scales (continental to regional level). Speciality green coffee beans were sourced from three continents, eight countries, and 22 regions. The dispersive bulk NIR spectra were used for spectral registration in the reflectance mode, and the obtained spectra were preprocessed with extended multiplicative scatter correction and mean centering. The classical linear partial least squares-discriminant analysis adequately predicted origin at the continental and country level, and showed promise at the regional level. Non-linear machine learning models improved predictions further, with the best accuracy found using random forest with accuracies up to 0.99. Discriminating wavelength regions and constituents were identified at each origin scale, with more minor wavelength regions selected by random forest. This proof of concept work demonstrated the potential of NIR spectroscopy coupled with machine learning for rapid origin classification of coffee from the continental to the regional level.

Synthesis and biological evaluation of imidazolium conjugated with dimethylcardamonin (DMC) as a novel potential agent against MDA-MB-231 triple-negative breast cancer cells

A new imidazolium ionic liquid (IL) halide conjugated with dimethylcardamonin (DMC, 1), namely [Bbim]Br-DMC (3), was synthesised to improve the biological activity of the natural chalcone. DMC was isolated from seeds of Syzygium nervosum A. Cunn. ex DC. which was an effective anti-breast cancer agent. The compound 1 and 3 showed anticancer activity in MDA-MB-231 cells with IC50 values of 14.54 ± 0.99 μM and 7.40 ± 0.15 μM, respectively. MTT assay showed that compound 3 had cytotoxic effect at least two-fold greater than compound 1 but was low toxic to normal cells of Hs 578Bst. After 48 h, compound 3 at concentration of IC50 value inhibited the proliferation and induced morphological changes of MDA-MB-231 cells in a time-dependent manner. The cell cycle profile also showed that compound 3 exerted anti-proliferation activity with the cell cycle arrest at G0/G1 phase and compound 3 also induced apoptosis and reduced mitochondrial membrane potential in MDA-MB-231 cells in a dose-dependent manner. In gene expression assay, compound 3 up-regulated pro-apoptotic genes such as Bax and p53 and suppressed anti-apoptotic Bcl-2 whereas there was no effect on DNA repair gene such as PARP1. The Bax/Bcl-2 ratio was significantly increased after treated with compound 3. In the molecular docking study, the interactions between compound 3 and B-DNA structure in the minor groove region via hydrogen bonds was reported. In conclusion, [Bbim]Br-DMC or compound 3 is a potential candidate to induce apoptosis and inhibits proliferation via cell cycle arrest and decreases mitochondrial membrane of triple-negative breast cancer MDA-MB-231 cells.

6-Gingerol anti-inflammatory and antioxidant properties protect against heart and liver dysfunction in rats with sepsis

ObjectiveTo investigate the effect of 6-gingerol, active component of Zingiber officinale (Shēngjiāng), on sepsis-induced inflammation, oxidative injury, and organ damage in vivo. Methods6-gingerol was extracted from ginger, and its identity was confirmed with 1H NMR, 13C NMR, and TLC. Sepsis was induced via cecal ligation and puncture (CLP) in all groups except for sham. Thirty male Wistar rats were randomly divided into sham, CLP alone, 6-gingerol, ginger extract, hydrocortisone, and solvent. Treatments were administered intraperitoneally with a dose of 25 mg/kg. Biomarkers for inflammation, oxidative injury, and organ damage were assessed. Furthermore, heart and liver organs were stained with hematoxylin-eosin to determine the extent of sepsis-induced organ damage. Results6-gingerol with 98.9 % purity was extracted. Compared with CLP-alone, biomarker analyses indicated that 6-gingerol significantly attenuated sepsis-induced inflammation by decreasing the levels of tumor necrosis factor-α, interleukin-6, and nuclear factor-κB. Furthermore, this bioactive constituent markedly reduced oxidative stress during sepsis by replenishing the levels of glutathione, increasing catalase, and decreasing malondialdehyde and superoxide. Moreover, organ damage assays showed that 6-gingerol substantially reduced the levels of cardiac troponin I, alanine aminotransaminase, aspartate aminotransferase, and lactate dehydrogenase, showing protective effects against cardiac and hepatic dysfunction. Similarly, rats treated with 6-gingerol had normal hepatic lobules, fewer Kupffer cells in minor regions of the liver, and lower necrosis and apoptosis in the myocardium. Discussion6-gingerol protects both heart and liver organs through its anti-inflammatory and antioxidant effects in septic rats.

Elucidating the Interaction of Indole-3-Propionic Acid and Calf Thymus DNA: Multispectroscopic and Computational Modeling Approaches.

Indole-3-propionic acid (IPA) is a plant growth regulator with good specificity and long action. IPA may be harmful to human health because of its accumulation in vegetables and fruits. Therefore, in this study, the properties of the interaction between calf thymus DNA (ctDNA) and IPA were systematically explored using multispectroscopic and computational modeling approaches. Analysis of fluorescence spectra showed that IPA binding to ctDNA to spontaneously form a complex was mainly driven by hydrogen bonds and hydrophobic interaction. DNA melting analysis, viscosity analysis, DNA cleavage study, and circular dichroism measurement revealed the groove binding of IPA to ctDNA and showed that the binding did not significantly change ctDNA confirmation. Furthermore, molecular docking found that IPA attached in the A-T rich minor groove region of the DNA. Molecular dynamics simulation showed that DNA and IPA formed a stable complex and IPA caused slight fluctuations for the residues at the binding site. Gel electrophoresis experiments showed that IPA did not significantly disrupt the DNA structure. These findings may provide useful information on the potential toxicological effects and environmental risk assessments of IPA residue in food at the molecular level.

#341 Dialysis modality patterns across six continents in Apollo Dial DB

Abstract Background and Aims Data is often collected during kidney dialysis treatments, providing data on a large scale and at a constant flow. As multinational datasets are scarce, Apollo Dial DB was created by a global provider that contains longitudinal observational data across six continents. This database is fully anonymised and can be used to better understand modality practice of global patients from a variety of healthcare systems for quality improvement and research efforts. Our aim was to detail patterns of dialysis modalities used among patients treated in 40 countries across six continents represented in the first version of the global database. Method Apollo Dial DB, a global anonymised dialysis database, contains demographics, diagnoses, laboratories, medications, treatments, quality of life, and outcomes from six continents and 40 countries. Data was harmonised from different electronic systems and anonymised based on logic established in a re-identification risk assessment. Data is consolidated and stored in a central cloud environment. The initial version of the dataset contains data on more than 360 variables from January 2018 to March 2021 and will be updated periodically. Results The first version of the Apollo Dial DB includes data on 543,169 patients, with 4.6% from Asia-Pacific (AP), 13.9% from Europe, Middle East, and Africa (EMEA), 7.0% from Latin America (LA), and 74.5% from North America (NA) countries. Most of the patients included in the database are between 45-64 years old at the initiation of dialysis. Overall, Apollo Dial DB contains information on 140,016,249 dialysis treatment observations. Depending on the region, different treatment patterns could be observed (Table 1 and Fig. 1). In EMEA a higher proportion of patients received hemodiafiltration with post-dilution, especially in Northern and Southern Europe as well as in South Africa. Peritoneal dialysis was more frequently used in LA and NA than in other regions. CCPD was mainly used in NA, whereas CAPD was common in LA and EMEA. For a more detailed look across the six continents Fig. 1 illustrates incentre hemodialysis modality patterns on a minor world region level. For incentre hemodialysis treatments, the majority of treatments from the minor regions in AP, LA, and NA had HD treatments. However, the majority treatments from EMEA minor regions are receiving incentre HDF treatments. Conclusion In a descriptive analysis, we defined modality treatment patterns in major world regions. These findings act as benchmarks for the nephrology community and expand upon scarce point prevalent information on modality practice patterns used throughout the world [1]. Apollo Dial DB offers opportunities for investigators to conduct global analytics and advance the state of the art.

#1157 Body mass and fluid balance in dialysis: global profiles in Apollo Dial DB

Abstract Background and Aims Fluid management is a fundamental component of dialysis care. Achieving euvolemia and avoiding fluid overload can be challenging in dialysis. Apollo Dial DB, an anonymised dialysis database from a global kidney care network, was used to gain deeper insights in patterns of patient body mass and fluid balance during dialysis treatments worldwide. Method Apollo Dial DB, a global anonymised dialysis database, contains real-world data from patients in 40 countries beginning January 2018 throughout March 2021. Parameters include demographics, diagnoses, laboratories, medications, treatments, quality of life, and outcomes. This analysis assessed body mass and fluid status parameters on patients in Asia-Pacific (AP), Europe, Middle East, and Africa (EMEA), Latin America (LA), Northern America (NA). In addition, bioimpedance for body compositions of patients was assessed as it was available in AP, EMEA, and LA. Results The first version of the Apollo Dial DB includes data on 543, 169 patients, with 4.6% from AP, 13.9% from EMEA, 7.0% from LA, and 74.5% from NA countries. EMEA and NA have a higher proportion of patients in the bigger height categories versus the AP and LA regions (Table 1). There is a difference in mean body weight post dialysis of more than 10 kg between regions; the highest weights were observed in EMEA and NA in contrast to the AP and LA regions. Average albumin levels were consistent in all global regions. Intradialytic weight gain is lowest in EMEA at 1.8 kg and highest in NA at 2.2 kg between treatments. While ultrafiltration volume ranged from 2.0 L to 2.4 L, being the highest in AP and NA. Bioimpedance measures defining body compositions were available for the majority of patients in AP (59.3%), EMEA (86.9%), and LA (90.7%). Patient averages in EMEA are slightly higher for ATM, FTM, LTM, TBW than for LA and AP; this is somewhat explained by the differences in body weight between the cohorts (Fig. 1). Conclusion A descriptive analysis of the body mass and fluid status across minor and major regions bring to light key profiles and differences in the characteristics of dialysis patients across the world and fluid management practices in dialysis care. Differences in intradialytic weight gain may deserve further analysis considering the impact of dialysis modality on fluid balance, such as potential influences of convective therapies. These findings act as benchmarks for the nephrology community. Apollo Dial DB offers opportunities for investigators to conduct global analytics and advance kidney disease research.

In-vitro and in-silico analysis and antitumor studies of novel Cu(II) and V(V) complexes of N-p-Tolylbenzohydroxamic acid

Copper(L2Cu) and vanadium(L2VOCl) complexes of N-p-tolylbenzohydroxamic acid (LH) ligand have been investigated for DNA binding efficacy by multiple analytical, spectral, and computational techniques. The results revealed that complexes as groove binders as evidenced by UV absorption. Fluorescence studies including displacement assay using classical intercalator ethidium bromide as fluorescent probe also confirmed as groove binders. The viscometric analysis too supports the inferences as strong groove binders for both the complexes. Molecular docking too exposed DNA as a target to the complexes which precisely binds L2Cu, in the minor groove region while L2VOCl in major groove region. Molecular dynamic simulation performed on L2Cu complex revealing the interaction of complex with DNA within 20 ns time. The complex stacked into the nitrogen bases of oligonucleotides and the bonding features were intrinsically preserved for longer simulation times. In-vitro cytotoxicity study was undertaken employing MTT assay against the breast cancer cell line (MCF-7). Potential cytotoxic activities were observed for L2Cu and L2VOCl complexes with IC50 values of showing 71 % and 74 % of inhibition respectively.

Genome-wide association analysis of eggshell color of an F2 generation population reveals candidate genes in chickens

Eggshell color is an important visual characteristic that affects consumer preferences for eggs. Eggshell color, which has moderate to high heritability, can be effectively enhanced through molecular marker selection. Various studies have been conducted on eggshell color at specific time points. However, few longitudinal data are available on eggshell color. Therefore, the objective of this study was to investigate eggshell color using the Commission International de L'Eclairage L*a*b* system with multiple measurements at different ages (age at the first egg and at 32, 36, 40, 44, 48, 52, 56, 60, 66, and 72 weeks) within the same individuals from an F2 resource population produced by crossing White Leghorn and Dongxiang Blue chicken. Using an Affymetrix 600 single nucleotide polymorphism (SNP) array, we estimated the genetic parameters of the eggshell color trait, performed genome-wide association studies (GWASs), and screened for the potential candidate genes. The results showed that pink-shelled eggs displayed a significant negative correlation between L* values and both a* and b* values. Genetic heritability based on SNPs showed that the heritability of L*, a*, and b* values ranged from 0.32 to 0.82 for pink-shelled eggs, indicating a moderate to high level of genetic control. The genetic correlations at each time point were mostly above 0.5. The major-effect regions affecting the pink eggshell color were identified in the 10.3–13.0 Mb interval on Gallus gallus chromosome 20, and candidate genes were selected, including SLC35C2, PCIF1, and SLC12A5. Minor effect polygenic regions were identified on chromosomes 1, 6, 9, 12, and 15, revealing 11 candidate genes, including MTMR3 and SLC35E4. Members of the solute carrier family play an important role in influencing eggshell color. Overall, our findings provide valuable insights into the phenotypic and genetic aspects underlying the variation in eggshell color. Using GWAS analysis, we identified multiple quantitative trait loci (QTLs) for pink eggshell color, including a major QTL on chromosome 20. Genetic variants associated with eggshell color may be used in genomic breeding programs.

Dissection of the E8 locus in two early maturing Canadian soybean populations.

Soybean [Glycine max (L.) Merr.] is a short-day crop for which breeders want to expand the cultivation range to more northern agro-environments by introgressing alleles involved in early reproductive traits. To do so, we investigated quantitative trait loci (QTL) and expression quantitative trait loci (eQTL) regions comprised within the E8 locus, a large undeciphered region (~7.0 Mbp to 44.5 Mbp) associated with early maturity located on chromosome GM04. We used a combination of two mapping algorithms, (i) inclusive composite interval mapping (ICIM) and (ii) genome-wide composite interval mapping (GCIM), to identify major and minor regions in two soybean populations (QS15524F2:F3 and QS15544RIL) having fixed E1, E2, E3, and E4 alleles. Using this approach, we identified three main QTL regions with high logarithm of the odds (LODs), phenotypic variation explained (PVE), and additive effects for maturity and pod-filling within the E8 region: GM04:16,974,874-17,152,230 (E8-r1); GM04:35,168,111-37,664,017 (E8-r2); and GM04:41,808,599-42,376,237 (E8-r3). Using a five-step variant analysis pipeline, we identified Protein far-red elongated hypocotyl 3 (Glyma.04G124300; E8-r1), E1-like-a (Glyma.04G156400; E8-r2), Light-harvesting chlorophyll-protein complex I subunit A4 (Glyma.04G167900; E8-r3), and Cycling dof factor 3 (Glyma.04G168300; E8-r3) as the most promising candidate genes for these regions. A combinatorial eQTL mapping approach identified significant regulatory interactions for 13 expression traits (e-traits), including Glyma.04G050200 (Early flowering 3/E6 locus), with the E8-r3 region. Four other important QTL regions close to or encompassing major flowering genes were also detected on chromosomes GM07, GM08, and GM16. In GM07:5,256,305-5,404,971, a missense polymorphism was detected in the candidate gene Glyma.07G058200 (Protein suppressor of PHYA-105). These findings demonstrate that the locus known as E8 is regulated by at least three distinct genomic regions, all of which comprise major flowering genes.

Sulfide compositions of young Chang’e-5 basalts and implications for sulfur isotopes in lunar basalt sources

Sulfides are accessory phases in lunar rocks butare important forunderstanding lunar interior processes as well as impacts on the lunar surface.Whether or not the lunar mantle had achieved sulfide saturation during magma ocean evolution and displays homogeneous sulfur isotopes remains under debate. TheChang’e-5 (CE-5) mission returned young (2.0 Ga) basalts from a mare terrain in thenorthern Oceanus Procellarum.Here we study chemical and sulfur isotopic compositions (δ34SV-CDT) of sulfides from CE-5 basaltic fragments and combine them with δ34S of other young (3.1–3.0 Ga) lunar low-Ti basalt (NWA 10597 and NWA 4734) and gabbro meteorites (NWA 6950) to compare them with Apollo low-Ti and high-Ti mare basalts. The sulfides in basaltic fragments of CE-5 are troilites (FeS) with lowabundances ofNi, Co, and Cu(e.g., Ni < 0.04 wt% and Ni/Co < 0.3). Textures and chemical compositions indicate that most troilites arelate-stage crystallization products fromthe highly evolvedCE-5 basalts. Several troilites occur in the matrices of impactite clasts and are intergrown with Fe–Ni metal(12–36 wt% Ni, Ni/Co of 12–39). These troilites are distinct from the major population of troilites withnoticeably higher Ni abundances (mostly > 0.2 wt% with Ni/Co of 1–3) andreconcile with the addition of meteoritic materials into the impact melts.The δ34SV-CDTof large troilite grains (>10 μm) from the CE-5 basaltic fragments and lunar meteorites were obtained by high-precision, high-spatial-resolution femtosecond laser ablation MC-ICP-MS which achieved external uncertainty (0.65 ‰, 2SD at 8-μm laser spots) like nano-SIMS. Sulfur degassing during surficial effusive lava flow likely led to a slightdecrease inδ34S (by ∼ 1 ‰) for some basaltic fragments; however, such effects were limited to the scale of bulk rock samples, consistent with previous results. The mean δ34Sof troilites in CE-5 basaltic fragments (0.35 ± 0.25 ‰, 2SE, n = 45) is similar to those of ancient (3.8–3.1 Ga old) Apollo low-Ti and high-Ti mare basalts and the young gabbro cumulate NWA 6950 (0.56 ± 0.21 ‰, 2SE, n = 10). The paired NWA 10597 and NWA 4734 show consistent δ34S, lower than most values by ∼ 0.5 ‰. Current data thus indicate that most mantle sources of lunar basalts would be homogeneous for δ34S(0.6 ± 0.3 ‰) and minor regions may be different. The overall homogenous δ34S from different mantle sources with variably low sulfur contents supports sulfide-undersaturated accumulation of the lunar magma ocean, which was inherited from strong volatile loss and evaporative fractionation during the formation of the Moon.

Impact of temperature on the binding interaction between dsDNA and curcumin: An electrochemical study

In this study, we investigated the binding mode between double-stranded deoxyribonucleic acid (dsDNA) and curcumin (CU) using differential pulse voltammetry (DPV), UV–Vis spectroscopy, and molecular docking. By employing these techniques, we predicted the binding within the minor groove region of dsDNA and CU. Significantly, we employed electrochemistry, specifically cyclic voltammetry (CV), to explore the temperature effect on the dsDNA and CU binding. To the best of our knowledge, this is the first study to utilize electrochemical methods for investigating the temperature-dependent behavior of this binding interaction. Our findings revealed temperature-dependent variations in the binding constants: 2.42 × 103 M−1 at 25 °C, 4.26 × 103 M−1 at 30 °C, 5.44 × 103 M−1 at 35 °C, 6.29 × 103 M−1 at 40 °C, and 7.52 × 103 M−1 at 45 °C. Notably, the binding constant exhibited an increasing trend with elevated temperatures, indicating a temperature-dependent enhancement of the binding interaction.

Continuous clinicopathological and molecular recognition of very virulent infectious bursal disease virus in commercial broiler chickens

Gumboro virus is one of the most dangerous immunosuppressant viruses that infect chickens and causes massive financial losses around the world. The purpose of the current study is to conduct a molecular survey of chicken farms for the infectious bursal disease virus (IBDV). On the basis of postmortem (PM) lesions, 125 bursal samples from 25 farms were collected from clinically diseased commercial chicken farms with increased mortality and suspected Gumboro virus infection. Pooled bursal samples from suspected IBD-vaccinated flocks were tested for IBDV by real-time polymerase chain reaction (RT-PCR). Fifteen out of 25 pooled specimens were found positive for IBDV, with a 60% detection rate, and confirmed positive for very virulent IBDV (vvIBDV). Nucleotide phylogenetic analysis of VP1 and VP2 genes was employed to compare the five chosen isolates with strains identified in various localities in 2022. The VP1 and VP2 genes are allotted into groups (I, II). The strains in our study were related to group II and it acquired a new mutation in the VP2 gene that clustered it into new subgroup B. By mutation analysis, the VP2 gene of all strains had a characteristic mutation to vvIBDV. It acquired new mutations in HVRs contrasted with HK64 in Y220F, A222T/V in all strains in our study, and Q221K that was found in IBD-EGY-AH5 and AH2 in the major hydrophilic region peak A in the loop PBC in addition to G254S in all strains in our study and Q249k that found in IBD-EGY-AH1 and AH3 in the minor hydrophilic region 1 in the loop PDE. These mutations are important in the virulency and antigenicity of the virus. The VP1 had 242E and 390L were characteristic of vvIBDV and KpnI restriction enzyme (777GGTAC/C782) in addition to a new mutation (F243Y and N383H) in tIBD-EGY-AH1 and AH4 strains. According to the current study, the strains were distinct from the vaccinal strain; they could be responsible for the most recent IBDV outbreaks observed in flocks instead of received vaccinations. The current study highlighted the importance of regular IBD monitoring to maintain up to date on the type of challenge viruses and the efficacy of commercial vaccinations.

Synthesis, characterization and multi-spectroscopic DNA/HSA interaction studies of synthetic human Follicle-Stimulating Hormone Beta 33–53 peptide conjugated PEGylated graphene oxide nanoparticles

The objective of the current study was to synthesize, characterize and explore the interaction of PEGylated graphene oxide (pGO) and synthetic human Follicular stimulating hormone β 33–53 peptide conjugated PEGylated graphene oxide nanoparticles (pGO-FSH) with human serum albumin (HSA) and calf thymus DNA (CT-DNA). The pGO/ pGO-FSH nanoparticles were synthesized using a modified Hummer’s method, and the FSH peptide was conjugated through a maleimide crosslinking reaction. Synthesized nanoparticles were then characterized using techniques like FT-IR, UV–Visible absorbance, CD and Raman spectroscopy, and XRD and TGA. Morphological and particle size analysis was studied using SEM, TEM, DLS, and zeta potential measurements. The presence of FSH β 33–53 peptide was confirmed qualitatively and quantitatively using CD spectroscopy and Bradford’s assay. Binding studies of pGO/pGO-FSH nanoparticles with HSA and DNA were carried out using biophysical techniques. The complex formation between pGO/pGO-FSH nanoparticles and HSA was revealed by UV absorbance spectroscopy, and the observed fluorescence quenching was confirmed by steady-state fluorescence spectroscopy. Time-resolved fluorescence quenching studies have shown that dynamic quenching plays an important role in binding HSA with pGO/pGO-FSH nanoparticles. However, structurally no significant changes were observed in the native structure of HSA upon binding with pGO/pGO-FSH nanoparticles suggesting that the latter did not induce any structural distortions together, confirmed by DSC, FT-IR, and CD spectroscopy experimental findings. Binding constants and thermodynamic parameters calculated using double logarithmic and Van’t Hoff plots suggested weak and moderate binding affinity along with the involvement of hydrophobic and hydrogen bonding interactions between HSA and pGO/pGO-FSH nanoparticles, respectively. UV absorbance and fluorescence spectroscopy have revealed that pGO/pGO-FSH nanoparticles interact with DNA by binding at the minor groove region. These findings were further confirmed by DNA melting and viscosity studies. CD and FT-IR spectroscopy studies have shown no changes in the helical structure of B-form of DNA, thereby emphasizing the groove-binding nature of pGO/pGO-FSH nanoparticles. The obtained results are useful in further considering the potentiality of pGO-FSH nanoparticles as drug-delivery systems for in vivo applications, especially to target ovarian cancer.

Regional biomechanical characterization of human ascending aortic aneurysms: Microstructure and biaxial mechanical response.

The ascending thoracic aortic aneurysm (ATAA) is a permanent dilatation of the vessel with a high risk of adverse events, and shows heterogeneous properties. To investigate regional differences in the biomechanical properties of ATAAs, tissue samples were collected from 10 patients with tricuspid aortic valve phenotype and specimens from minor, anterior, major, and posterior regions were subjected to multi-ratio planar biaxial extension tests and second-harmonic generation (SHG) imaging. Using the data, parameters of a microstructure-motivated constitutive model were obtained considering fiber dispersion. SHG imaging showed disruptions in the organization of the layers. Structural and material parameters did not differ significantly between regions. The non-symmetric fiber dispersion model proposed by Holzapfel etal. [25] was used to fit the data. The mean angle of collagen fibers was negatively correlated between minor and anterior regions, and the parameter associated with collagen fiber stiffness was positively correlated between minor and major regions. Furthermore, correlations were found between the stiffness of the ground matrix and the mean fiber angle, and between the parameter associated with the collagen fiber stiffness and the out-of-plane dispersion parameter in the posterior and minor regions, respectively. The experimental data collected in this study contribute to the biomechanical data available in the literature on human ATAAs. Region-specific parameters for the constitutive models are fundamental to improve the current risk stratification strategies, which are mainly based on aortic size. Such investigations can facilitate the development of more advanced finite element models capable of capturing the regional heterogeneity of pathological tissues. STATEMENT OF SIGNIFICANCE: Tissue samples of human ascending thoracic aortic aneurysms (ATAA) were collected. Samples from four regions underwent multi-ratio planar biaxial extension tests and second-harmonic generation imaging. Region-specific parameters of a microstructure-motivated model considering fiber dispersion were obtained. Structural and material parameters did not differ significantly between regions, however, the mean fiber angle was negatively correlated between minor and anterior regions, and the parameter associated with collagen fiber stiffness was positively correlated between minor and major regions. Furthermore, correlations were found between the stiffness of the ground matrix and the mean fiber angle, and between the parameter associated with the collagen fiber stiffness and the out-of-plane dispersion parameter in the posterior and minor regions, respectively. This study provides a unique set of mechanical and structural data, supporting the microstructural influence on the tissue response. It may facilitate the development of better finite element models capable of capturing the regional tissue heterogeneity.

Correlation of t(14;18) translocation breakpoint site with clinical characteristics in follicular lymphoma.

t(14;18)(q32;q21) translocation is an important genetic feature of follicular lymphoma resulting in antiapoptotic B-cell lymphoma 2 (BCL2) protein overexpression. On chromosome 18 breakpoint-site variation is high but does not affect BCL2. Breakpoint most commonly occurs at major breakpoint region (MBR) but may happen at minor cluster region (mcr) and between MBR and mcr at 3'MBR and 5'mcr. The aim of this study was to analyze the correlation of t(14;18)(q32;q21) breakpoint site with clinical characteristics in follicular lymphoma. We included patients diagnosed with follicular lymphoma who received at least 1 cycle of systemic treatment and had the t(14;18)(q32;q21) translocation detected by polymerase chain reaction (PCR) at MBR, mcr or 3'MBR prior to first treatment. Among patients with different breakpoints, sex, age, disease grade, stage, B-symptoms, follicular lymphoma international prognostic index (FLIPI), presence of bulky disease, progression free survival and overall survival were compared. Of 84 patients, 63 had breakpoint at MBR, 17 at mcr and 4 at 3'MBR. At diagnosis, the MBR group had a significantly lower disease stage than the mcr group. Although not significant, in the MBR group we found a higher progression-free survival (PFS) and overall survival (OS), lower grade, age, FLIPI, and less B-symptoms. Compared to patients with mcr breakpoint, those with MBR breakpoint seem to be characterised by more favourable clinical characteristics. However, a larger study would be required to support our observation.