DNA Methylation and Subgenome Dominance Reveal the Role of Lipid Metabolism in Jinhu Grouper Heterosis.

Heterosis of growth traits in economic fish has benefited the production of aquaculture for many years, yet its genetic and molecular basis has remained obscure. Nowadays, a new germplasm of hybrid Jinhu grouper (Epinephelus fuscoguttatus ♀ × E. tukula ♂), abbreviated as EFT, exhibiting paternal-biased growth heterosis, has provided an excellent model for investigating the potential regulatory mechanisms of heterosis. We integrated transcriptome and methylome to unravel the changes of gene expression, epigenetic modification, and subgenome dominance in EFT compared with maternal E. fuscoguttatus. Integration analyses showed that the heterotic hybrids showed lower genomic DNA methylation levels than the purebred parent, and the up-regulated genes were mostly DNA hypomethylation. Furthermore, allele-specific expression (ASE) detected paternal subgenome dominance-regulated paternal-biased heterosis, and paternal bias differentially expressed genes (DEGs) were wholly up-regulated in the muscle. Multi-omics results highlighted the role of lipid metabolism, particularly "Fatty acid synthesis", "EPA biosynthesis", and "Signaling lipids", in EFT heterosis formation. Coherently, our studies have proved that the eicosapentaenoic acid (EPA) of EFT was greater than that of maternal E. fuscoguttatus (8.46% vs. 7.46%). Finally, we constructed a potential regulatory network for control of the heterosis formation in EFT. Among them, fasn, pparg, dgat1, igf1, pomca, fgf8a, and fgfr4 were identified as key genes. Our results provide new and valuable clues for understanding paternal-biased growth heterosis in EFT, taking a significant step towards the molecular basis of heterosis.

Gold Nanoparticles Modulate Excimer and Exciplex Dynamics of PDDCP-Conjugated Polymers.

How plasmonic nanostructures modulate the behavior of exciplexes and excimers within materials remains unclear. Thus, advanced knowledge is essential to bridge this gap for the development of optoelectronic devices that leverage the interplay between plasmonic and conjugated polymer hybrid materials. Herein, this work aims to explore the role of gold nanoparticles (AuNPs) in modulating exciplex and excimer states within the conjugated polymer poly(2,5-di(3,7-dimethyloctyloxy) cyanoterephthalylidene) (PDDCP), known for its photoluminescent and semi-conductive properties, aiming to create innovative composite materials with tailored optical features. The spectral analysis was conducted to investigate the effects of AuNPs on the PDDCP, varying AuNP volume percentages to measure changes in the absorption profile, molar extinction coefficient (ε), absorption cross-section (σa), and optical bandgap (Eg). Fluorescence spectra of the mixture at different volume ratios were also examined to assess exciplex formation, while amplified spontaneous emission (ASE) profiles were analyzed to study the behavior and photochemical stability of the polymer-NP hybrid material. Increasing AuNP volume induced both blue and red shifts in the absorption profile of the PDDCP. Higher AuNPs concentrations correlated with decreased ε and σa, inversely impacting Eg. The emission spectra obtained at varied AuNP volume ratios indicated significantly enhanced exciplex and excimer formations. The ASE profiles remained consistent but showed reduced intensity with increasing AuNPs concentrations, indicating their influence on hybrid material behavior and stability. The findings suggest that AuNPs affect PDDCP's optical characteristics, altering the absorption profile, bandgap, and fluorescence spectra. Furthermore, the observed reduction in ASE intensity highlights their influence on the behavior and photochemical stability of the hybrid material. These results contribute to a better understanding of the versatile applications of plasmonic-conjugated hybrid polymers.

Geospatial Mapping and Seasonal Profiling of Urinary Schistosomiasis in Ase-Niger River Settlements: A Data-Driven Population-Base Study in Delta State, Nigeria.

OBJECTIVES: This study is aimed to determine the geospatial, seasonal, age and gender prevalence and intensity of UgS; and to establish disease maps in the Ase-Niger River communities for effective drug administration. STUDY DESIGN: This study employed a 24 months longitudinal study design for parasitological investigations in 11 riparian communities of the Ase-Niger River basin, taking into cognizance their GPS locations imported into QGIS software for schistosomiasis mapping. METHODS: A total of 7,219 urine samples with WHO structured questionnaires were retrieved and subjected to parasitological evaluation using swinnex urine filtration techniques. RESULTS: An overall prevalence of 48.10% was established. Geospatially, prevalence ranges from 34.27% (Ivrogbo) to 52.29% (Ase) with seasonal significant difference (p < 0.05) accounting for 76.19% of the total variance. Ashaka had the highest prevalence for both males (55.73%) and females (53.32%) with significant difference in the study sites (p < 0.05) accounting for 96.47% of the total variance. Age-group 11-20 years consistently maintain a high prevalence at all sites. The peak geometric mean intensity of 105.69 was obtained in the dry season at Lagos Iyede. Ashaka, Igbuku, Iyede-Ame, and Onogboko had heavy-intensity levels in both seasons. Overall, the intensity was lower during the wet season than the dry season, with significant variations (p < 0.05) at Awah and Itobi-Ige. Geospatial prevalence and intensity have a robust and strong positive correlation (r = 0.7178; p = 0.0129), with 51.53% of intensity variability being influenced by prevalence (R2 = 0.5153). CONCLUSION: UgS is a significant public health issue in the Ase-Niger River basin, with prevalences surpassing the national average of 29.0% which calls for MDA in these settlements.

Ase1 selectively increases the lifetime of antiparallel microtubule overlaps.

Microtubules (MTs) are dynamically unstable polar biopolymers switching between periods of polymerization and depolymerization, with the switch from the polymerization to the depolymerization phase termed catastrophe and the reverse transition termed rescue.1 In presence of MT-crosslinking proteins, MTs form parallel or anti-parallel overlaps and self-assemble reversibly into complex networks, such as the mitotic spindle. Differential regulation of MT dynamics in parallel and anti-parallel overlaps is critical for the self-assembly of these networks.2,3 Diffusible MT crosslinkers of the Ase1/MAP65/PRC1 family associate with different affinities to parallel and antiparallel MT overlaps, providing a basis for this differential regulation.4,5,6,7,8,9,10,11 Ase1/MAP65/PRC1 family proteins directly affect MT dynamics12 and recruit other proteins that locally alter MT dynamics, such as CLASP or kinesin-4.7,13,14,15,16 However, how Ase1 differentially regulates MT stability in parallel and antiparallel bundles is unknown. Here, we show that Ase1 selectively promotes antiparallel MT overlap longevity by slowing down the depolymerization velocity and by increasing the rescue frequency, specifically in antiparallelly crosslinked MTs. At the retracting ends of depolymerizing MTs, concomitant with slower depolymerization, we observe retention and accumulation of Ase1 between crosslinked MTs and on isolated MTs. We hypothesize that the ability of Ase1 to reduce the dissociation of tubulin subunits is sufficient to promote its enrichment at MT ends. A mathematical model built on this idea shows good agreement with the experiments. We propose that differential regulation of MT dynamics by Ase1 contributes to mitotic spindle assembly by specifically stabilizing antiparallel overlaps, compared to parallel overlaps or isolated MTs.

Er3+/Yb3+ Co-Doped Fluorotellurite Glass Fiber with Broadband Luminescence.

In order to address the 'capacity crisis' caused by the narrow bandwidth of the current C band and the demand for wide-spectrum sensing sources and tunable fiber lasers, a broadband luminescence covering the C + L bands using Er3+/Yb3+ co-doped fluorotellurite glass fiber is investigated in this paper. The optimal doping concentrations in the glass host were determined based on the intensity, lifetime, and full width at half maximum (FWHM) of the fluorescence centered at 1.5 µm, which were found to be 1.5 mol% Er2O3 and 3 mol% Yb2O3. We also systematically investigated this in terms of optical absorption spectra, absorption and emission cross-sections, gain coefficients, Judd-Ofelt parameters, and up-conversion fluorescence. The energy transfer (ET) mechanism between the high concentrations of Er3+ and Yb3+ was summarized. In addition, a step-indexed fiber was prepared based on these fluorotellurite glasses, and a wide bandwidth of ~112.5 nm (covering the C + L bands from 1505.1 to 1617.6 nm) at 3 dB for the amplified spontaneous emission (ASE) spectra has been observed at a fiber length of 0.57 m, which is the widest bandwidth among all the reports based on tellurite glass. Therefore, this kind of Er3+/Yb3+ co-doped fluorotellurite glass fiber has great potential for developing broadband C + L band amplifiers, ultra-wide fiber sources for sensing, and tunable fiber lasers.

Impact of water quality and morphometric indices on the spatio-temporal prevalence of fish endo-parasites and diversity in the Ase River, Niger-Delta, Nigeria.

Three stations along the Ase River, Delta State Nigeria provided water and 85 fish samples which were analyzed. The fish were measured and examined for endoparasites according to established protocol. All water quality parameters investigated were within the WHO-acceptable values for surface waters. Station variation of physicochemical parameters was not statistically significant (p > 0.05). Fish body conformation indices positively correlated with the prevalence of parasites in Clarias gariepinus, Heterobranchus longifilis, Parachana africana, Chromidotilapia guntheri guntherii, and Denticeps clupeodes. The overall parasite prevalence of 63.53% was established with the most abundant parasite being Trichodina mutabillis. The parasites had a predilection for the gastrointestinal tract with a high occurrence of 307 individuals. Stations 1, 2, and 3 had 326, 213, and 259 parasites, respectively, out of a total of 798 parasites detected. P. laevis was absent in station 1. All parasites were found in stations 2 and 3. Statistically, there was a significant difference (p < 0.05) in the prevalence in all stations. The correlation index of T. mutabillis and R. congolensis in stations 1 and 3 was positively strong (p < 0.05) with the concentrations of water quality. However, water conditions in stations 1 and 3 had a deleterious impact on P. laevis. T. mutabillis maintained a high positive correlation with physicochemical water quality in all three stations. Shannon-Weiner's index in station 3 (H = 1.337) shows that the parasites were more diverse. PCA and biodiversity indices have enabled us to comprehend how parasite-host-environment systems interact.

Analysis of Diffracted Mode Outcoupling in the Context of Amplified Spontaneous Emission of Organic Thin Films.

The existence of amplified spontaneous emission (ASE) is a fundamental principle of laser dyes. ASE indicates the spectral variation of the optical gain of a laser dye. Analyzing the spectral distribution of ASE is important for designing lasers. We demonstrate ASE investigations on planar waveguides made of a (co-)polymer. Similar to organic DFB (distributed feedback) lasers, a line grating allows a partial decoupling of the guided radiation. This decoupled radiation is detected as an indicator of the guided radiation. The diffraction of the radiation is utilized to perform a spectrally selective investigation of the ASE by spatially splitting it. This analysis method reduces the influence of isotropic photoluminescence and allows ASE to be analyzed across its entire spectrum. We were able to observe ASE in F8BT over a range from λASE,min = 530 nm to λASE,max = 570 nm and determine ASE threshold power densities lower than EASE< 2.57 µJ/cm2. The study of the power density of the ASE threshold is performed spectrally selectively.

Optimizing the Extraction of the Polyphenolic Fraction from Defatted Strawberry Seeds for Tiliroside Isolation Using Accelerated Solvent Extraction Combined with a Box-Behnken Design.

Tiliroside is a natural polyphenolic compound with a wide range of biological activity, and defatted strawberry seeds are its rich source. The goal of this study was to optimize accelerated solvent extraction (ASE) conditions, including temperature, solvent composition, and the number of extraction cycles, using Box-Behnken design to maximize the yield of tiliroside. UPLC-DAD-MS was applied to investigate the polyphenolic composition of the extracts, and preparative liquid chromatography (pLC) was used for isolation. All obtained mathematical models generally showed an increase in the efficiency of isolating polyphenolic compounds with an increase in temperature, ethanol content, and the number of extraction cycles. The optimal established ASE conditions for tiliroside were as follows: a temperature of 65 °C, 63% ethanol in water, and four extraction cycles. This allowed for the obtainment of a tiliroside-rich fraction, and the recovery of isolated tiliroside from plant material reached 243.2 mg from 100 g. Our study showed that ASE ensures the isolation of a tiliroside-rich fraction with high effectiveness. Furthermore, defatted strawberry seeds proved to be a convenient source of tiliroside because the matrix of accompanying components is relatively poor, which facilitates separation.

Quantitative Analysis of Isopimpinellin from Ammi majus L. Fruits and Evaluation of Its Biological Effect on Selected Human Tumor Cells.

Ammi majus L. (Apiaceae) is a medicinal plant with a well-documented history in phytotherapy. The aim of the present work was to isolate isopimpinellin (5,8-methoxypsoralen; IsoP) from the fruit of this plant and evaluate its biological activity against selected tumor cell lines. The methanol extract obtained with the use of an accelerated solvent extraction (ASE) method was the most suitable for the quantitative analysis of coumarins in the A. majus fruit matrix. The coumarin content was estimated by RP-HPLC/DAD, and the amount of IsoP was found to be 404.14 mg/100 g dry wt., constituting 24.56% of the total coumarin fraction (1.65 g/100 g). This, along with the presence of xanthotoxin (368.04 mg/100 g, 22.36%) and bergapten (253.05 mg/100 g, 15.38%), confirmed A. majus fruits as an excellent source of these compounds. IsoP was isolated (99.8% purity) by combined liquid chromatography/centrifugal partition chromatography (LC/CPC) and tested for the first time on its antiproliferative activity against human colorectal adenocarcinoma (HT29, SW620), osteosarcoma (Saos-2, HOS), and multiple myeloma (RPMI8226, U266) cell lines. MTT assay results (96 h incubation) demonstrated a dose- and cell line-dependent decrease in cell proliferation/viability, with the strongest effect of IsoP against the Saos-2 cell line (IC50; 42.59 µM), medium effect against U266, HT-29, and RPMI8226 (IC50 = 84.14, 95.53, and 105.0 µM, respectively), and very weak activity against invasive HOS (IC50; 321.6 µM) and SW620 (IC50; 711.30 µM) cells, as well as normal human skin fibroblasts (HSFs), with IC50; 410.7 µM. The mechanistic study on the Saos-2 cell line showed that IsoP was able to reduce DNA synthesis and trigger apoptosis via caspase-3 activation. In general, IsoP was found to have more potency towards cancerous cells (except for HOS and SW620) than against healthy cells. The Selective Index (SI) was determined, underlining the higher selectivity of IsoP towards cancer cells compared to healthy cells (SI = 9.62 against Saos-2). All these results suggest that IsoP might be a promising molecule in the chemo-prevention and treatment of primary osteosarcoma.

Spatiotemporal and seasonal transmission dynamics of Schistosoma haematobium and snail infectivity in Ase River catchment, Delta State, Nigeria.

Bulinus are intermediate snail hosts of Schistosoma haematobium. Despite their vectorial role, the transmission dynamics and infectivity of these intermediate snail hosts remain understudied in the Ase River. This longitudinal study evaluated the geospatial and seasonal transmission patterns and infectivity of three S. haematobium vectors between November 2020 and October 2022 in the Ase River catchment, Delta State, Nigeria. Eleven (11) geospatial water contact coordinates were mapped for monthly spatiotemporal collection of Bulinus species along the Ase River and its catchment, for two years. Snail sampling was performed for 45 min at each study site using scooping/hand-picking techniques and subsequently counted, identified and recorded. Snails of the Bulinus genus were individually placed in a beaker containing distilled water and exposed to light to shed cercariae which were identified to be human schistosome type. The number of infected snails for each month and season was also documented to analyze the spatiotemporal and seasonal transmission dynamics of infectivity. Out of the 2345 Bulinus snails collected, a total of 41.45% were found to be infected with S. haematobium. The monthly infectivity of Bulinus snails varied significantly (P < 0.05) throughout the study period (P = < 0.0001; F = 23.11; df = 11). Further analysis showed a strong significant association (χ2 = 23.57; df = 11; p = 0.015) between the study years. The Principal Component Analysis (PCA) results suggest that Bulinus infectivity within the Ase River catchment area was primarily associated with the months of February and January. B. truncatus consistently had the highest transmission potential, followed by B. globosus and B. senegalensis. ANOVA confirms that the monthly/study site infectivity and transmission potential in B. truncates, B. globosus and S. senegalensis were statistically, significant (P < 0.05). These results demonstrated a clear distinction in the patterns and relationships between the different months in terms of snail infectivity and seasonal transmission potential. This understanding will help in the continuous monitoring and targeted interventions to control schistosomiasis transmission in Ase River.

Utility of Shear Wave Elastography for the Diagnosis of Plantar Fasciitis: Comparison Between Symptomatic and Asymptomatic Sides in Unilaterally Affected Patients.

INTRODUCTION: Plantar fasciitis (PF) can cause pain in the heel, which can affect everyday activities. While it often resolves on its own, diagnosing PF to rule out other hind foot conditions by imaging modality in cases of recurrence can be difficult. Methods such as MRI and ultrasonography are helpful, but the use of elastography, specifically shear wave elastography (SWE), as a tool for diagnosing PF is being studied. METHODOLOGY: This comparative observational study included patients over 18 years presenting with unilateral hind foot pain who were investigated using SWE. Exclusions comprised those who were bilaterally affected and with foot deformities, trauma history, or prior injection therapy. Patients' AOFAS Ankle-Hindfoot Scores were assessed along with visual analog scale (VAS) scores, followed by SWE examination of both heels. RESULTS: The study found no significant difference in the plantar fascia thickness between affected and unaffected sides, with a mean thickness of 4.3±0.8mm and 5.1±0.6mm, respectively. Shear wave velocity (SWV) was lower on the affected side, indicating reduced stiffness compared to the unaffected side. The Spearman rank test revealed strong direct correlations between SWV and both the VAS and HF-AOFAS scores on the affected side. CONCLUSION: The study observed that SWE enhances B-mode ultrasonography in detecting early PF even with normal plantar fascia thickness, offering a user-independent and reliable tool for treatment monitoring and correlation with functional and pain scores. Further research with larger populations can aid in developing a clinico-radiological classification system for PF, improving prognostication and treatment guidance.

Eco-Friendly Extraction: A green approach to maximizing bioactive extraction from pumpkin (Curcubita moschata L.).

The research focused on optimizing the accelerated solvent extraction (ASE) of carotenoids and polyphenols from pumpkin powder. The study optimized accelerated solvent extraction (ASE) of carotenoids and polyphenols from pumpkin powder. Using a mix of standard score (SS) and artificial neural network (ANN) methods, the extraction process was fine-tuned. The ANN model assessed extraction parameters' significance, achieving high predictability for total carotenoid content (TCC), total phenolic content (TPC), and free radical scavenging capacity (DPPH and ABTS methods). The analysis highlighted the most effective extraction at 50 % concentration, 120 °C temperature, 5 min duration, and 2 cycles, yielding high carotenoid and phenolic content (TCC 571.49 µg/g, TPC 7.85 mg GAE/g). HPLC-DAD profiles of the optimized ASE extract confirmed major carotenoids and phenolic compounds. Strong correlations were found between bioactive compounds and antioxidant activity, emphasizing potential health benefits.

The OsWRKY72-OsAAT30/OsGSTU26 module mediates reactive oxygen species scavenging to drive heterosis for salt tolerance in hybrid rice.

Hybrid rice (Oryza sativa) generally outperforms its inbred parents in yield and stress tolerance, a phenomenon termed heterosis, but the underlying mechanism is not completely understood. Here, we combined transcriptome, proteome, physiological, and heterosis analyses to examine the salt response of super hybrid rice Chaoyou1000 (CY1000). In addition to surpassing the mean values for its two parents (mid-parent heterosis), CY1000 exhibited a higher reactive oxygen species scavenging ability than both its parents (over-parent heterosis or heterobeltiosis). Nonadditive expression and allele-specific gene expression assays showed that the glutathione S-transferase gene OsGSTU26 and the amino acid transporter gene OsAAT30 may have major roles in heterosis for salt tolerance, acting in an overdominant fashion in CY1000. Furthermore, we identified OsWRKY72 as a common transcription factor that binds and regulates OsGSTU26 and OsAAT30. The salt-sensitive phenotypes were associated with the OsWRKY72paternal genotype or the OsAAT30maternal genotype in core rice germplasm varieties. OsWRKY72paternal specifically repressed the expression of OsGSTU26 under salt stress, leading to salinity sensitivity, while OsWRKY72maternal specifically repressed OsAAT30, resulting in salinity tolerance. These results suggest that the OsWRKY72-OsAAT30/OsGSTU26 module may play an important role in heterosis for salt tolerance in an overdominant fashion in CY1000 hybrid rice, providing valuable clues to elucidate the mechanism of heterosis for salinity tolerance in hybrid rice.

Bioinformatics analysis of the prognostic role of alternative splicing data in lung adenocarcinoma.

Background: As a post-transcriptional regulatory mechanism, alternative splicing (AS) is engaged in a variety of pathophysiological processes, and it has been widely reported in connection with the occurrence, progression, metastasis, and drug resistance of cancer. However, the research on AS in lung adenocarcinoma (LUAD) is very limited. In addition, the prognostic effect of AS event (ASE) on LUAD and its related mechanism are not clear. This study aimed to explore the role and potential prognostic value of ASE in LUAD. Methods: Relevant data and ASE datasets of the sample were acquired from The Cancer Genome Atlas (TCGA) and TCGASpliceSeq databases. We constructed a new prognostic criterion based on ASEs. Then, Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis were used to construct the model. Based on this model, the risk score of each ASE was calculated, and the reliability of this model was evaluated by Kaplan-Meier survival and receiver operating characteristic (ROC) curve analyses. Finally, these results were verified on different network platforms. Results: We identified seven types of ASEs related to survival. The prognostic risk model for ASEs was established. The Kaplan-Meier curve showed that compared to the low-risk group, the overall survival (OS) rate of LUAD patients in the high-risk group was lower. ROC curve analysis showed that the prognostic risk model of LUAD patients was well predicted, and the area under the curve (AUC) also confirmed this. Conclusions: This study screened the ASE related to the prognosis of LUAD patients, and provided a theoretical basis for further study of the correlation between ASE and the prognosis of LUAD patients. It has provided new ideas for developing new biomarkers and therapeutic targets for LUAD patients.

Adaptation of a Commercial NAD+ Quantification Kit to Assay the Base-Exchange Activity and Substrate Preferences of SARM1.

Here, we report an adapted protocol using the Promega NAD/NADH-Glo™ Assay kit. The assay normally allows quantification of trace amounts of both oxidized and reduced forms of nicotinamide adenine dinucleotide (NAD) by enzymatic cycling, but we now show that the NAD analog 3-acetylpyridine adenine dinucleotide (AcPyrAD) also acts as a substrate for this enzyme-cycling assay. In fact, AcPyrAD generates amplification signals of a larger amplitude than those obtained with NAD. We exploited this finding to devise and validate a novel method for assaying the base-exchange activity of SARM1 in reactions containing NAD and an excess of the free base 3-acetylpyridine (AcPyr), where the product is AcPyrAD. We then used this assay to study competition between AcPyr and other free bases to rank the preference of SARM1 for different base-exchange substrates, identifying isoquinoline as a highly effect substrate that completely outcompetes even AcPyr. This has significant advantages over traditional HPLC methods for assaying SARM1 base exchange as it is rapid, sensitive, cost-effective, and easily scalable. This could represent a useful tool given current interest in the role of SARM1 base exchange in programmed axon death and related human disorders. It may also be applicable to other multifunctional NAD glycohydrolases (EC 3.2.2.6) that possess similar base-exchange activity.

Comprehensive analyses of 435 goat transcriptomes provides insight into male reproduction.

A systematic analysis of genes related to reproduction is crucial for obtaining a comprehensive understanding of the molecular mechanisms that underlie male reproductive traits in mammals. Here, we utilized 435 goat transcriptome datasets to unveil the testicular tissue-specific genes (TSGs), allele-specific expression (ASE) genes and their uncharacterized transcriptional features related to male goat reproduction. Results showed a total of 1790 TSGs were identified in goat testis, which was the most among all tissues. GO enrichment analyses suggested that testicular TSGs were mainly involved in spermatogenesis, multicellular organism development, spermatid development, and flagellated sperm motility. Subsequently, a total of 95 highly conserved TSGs (HCTSGs), 508 middle conserved TSGs (MCTSGs) and 42 no conserved TSGs (NCTSGs) were identified in goat testis. GO enrichment analyses suggested that the HCTSGs and MCTSGs has a more important association with male reproduction than NCTSGs. Additionally, we identified 644 ASE genes, including 88 tissue-specific ASE (TS-ASE) genes (e.g., FSIP2, TDRD9). GO enrichment analyses indicated that both ASE genes and TS-ASE genes were associated with goat male reproduction. Overall, this study revealed an extensive gene set involved in the regulation of male goat reproduction and their dynamic transcription patterns. Data reported here provide valuable insights for a further improvement of the economic benefits of goats as well as future treatments for male infertility.

Evaluation of the Moonlighting Histone H3 Specific Protease (H3ase) Activity and the Dehydrogenase Activity of Glutamate Dehydrogenase (GDH).

The N-terminus of Histone H3 is proteolytically processed in aged chicken liver. A histone H3 N-terminus specific endopeptidase (named H3ase) has been purified from the nuclear extract of aged chicken liver. By sequencing and a series of biochemical methods including the demonstration of H3ase activity in bacterially expressed GDH, it was established that the H3ase activity was a moonlighting protease activity of glutamate dehydrogenase (GDH). However, the active site for the H3ase in the GDH remains elusive. Here, using cross-linking studies of the homogenously purified H3ase, we show that the GDH and the H3ase remain in the same native state. Further, the H3ase and GDH activities could be uncoupled by partial denaturation of GDH, suggesting strong evidence for the involvement of different active sites for GDH and H3ase activities. Through densitometry of the H3ase clipped H3 products, the H3ase activity was quantified and it was compared with the GDH activity of the chicken liver nuclear GDH. Furthermore, the H3ase mostly remained distributed in the perinuclear area as demonstrated by MNase digestion and immuno-localization of H3ase in chicken liver nuclei, as well as cultured mouse hepatocyte cells, suggesting that H3ase demonstrated regulated access to the chromatin. The present study thus broadly compares the H3ase and GDH activities of the chicken liver GDH.

Linearly Manipulating Color Emission via Anion Exchange Technology for High Performance Amplified Spontaneous Emission of Perovskites.

The most attractive advantages of all-inorganic cesium lead halide perovskites are their optical gain over broad spectral ranges through the visible spectrum, so are well suited to use in tunable lasers or broadband amplifiers. Most reported anion exchange reactions face a challenge to achieve the desired halogen-variable perovskites due to rapid and uncontrollable reactions and difficulty to synthesize directly. In this study, a simple vapor/solid anion exchange strategy is demonstrated for controlling the reaction process and realizing a wide range tuning of band gap and amplified spontaneous emission (ASE) wavelength, which exhibits a temperature-dependent anion exchange rate. By optimizing the reaction temperature at 90 °C, the ASE wavelength can be linearly manipulated by just controlling the reaction time. A clear quantitative relationship between ASE peak position and reaction time is achieved. Compares with the CsPbClBr2 film obtained via the liquid phase anion exchange method, the fabricated perovskite films obtained by vapor/solid anion exchange technology exhibit superior film quality and enhanced ASE performance. This work may have applications in the future using facile and controllable techniques to develop high-quality full-color visible lasers.

Patterns of Gene Expression, Splicing, and Allele-Specific Expression Vary among Macular Tissues and Clinical Stages of Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness, and elucidating its underlying disease mechanisms is vital to the development of appropriate therapeutics. We identified differentially expressed genes (DEGs) and differentially spliced genes (DSGs) across the clinical stages of AMD in disease-affected tissue, the macular retina pigment epithelium (RPE)/choroid and the macular neural retina within the same eye. We utilized 27 deeply phenotyped donor eyes (recovered within a 6 h postmortem interval time) from Caucasian donors (60-94 years) using a standardized published protocol. Significant findings were then validated in an independent set of well-characterized donor eyes (n = 85). There was limited overlap between DEGs and DSGs, suggesting distinct mechanisms at play in AMD pathophysiology. A greater number of previously reported AMD loci overlapped with DSGs compared to DEGs between disease states, and no DEG overlap with previously reported loci was found in the macular retina between disease states. Additionally, we explored allele-specific expression (ASE) in coding regions of previously reported AMD risk loci, uncovering a significant imbalance in C3 rs2230199 and CFH rs1061170 in the macular RPE/choroid for normal eyes and intermediate AMD (iAMD), and for CFH rs1061147 in the macular RPE/choroid for normal eyes and iAMD, and separately neovascular AMD (NEO). Only significant DEGs/DSGs from the macular RPE/choroid were found to overlap between disease states. STAT1, validated between the iAMD vs. normal comparison, and AGTPBP1, BBS5, CERKL, FGFBP2, KIFC3, RORα, and ZNF292, validated between the NEO vs. normal comparison, revealed an intricate regulatory network with transcription factors and miRNAs identifying potential upstream and downstream regulators. Findings regarding the complement genes C3 and CFH suggest that coding variants at these loci may influence AMD development via an imbalance of gene expression in a tissue-specific manner. Our study provides crucial insights into the multifaceted genomic underpinnings of AMD (i.e., tissue-specific gene expression changes, potential splice variation, and allelic imbalance), which may open new avenues for AMD diagnostics and therapies specific to iAMD and NEO.

Single-cell multiomics of the human retina reveals hierarchical transcription factor collaboration in mediating cell type-specific effects of genetic variants on gene regulation.

BACKGROUND: Systematic characterization of how  genetic variation modulates gene regulation in a cell type-specific context is essential for understanding complex traits. To address this question, we profile gene expression and chromatin accessibility in cells from healthy retinae of 20 human donors through single-cell multiomics and genomic sequencing. RESULTS: We map eQTL, caQTL, allelic-specific expression, and allelic-specific chromatin accessibility in major retinal cell types. By integrating these results, we identify and characterize regulatory elements and genetic variants effective on gene regulation in individual cell types. The majority of identified sc-eQTLs and sc-caQTLs display cell type-specific effects, while the cis-elements containing genetic variants with cell type-specific effects are often accessible in multiple cell types. Furthermore, the transcription factors whose binding sites are perturbed by genetic variants tend to have higher expression levels in the cell types where the variants exert their effects, compared to the cell types where the variants have no impact. We further validate our findings with high-throughput reporter assays. Lastly, we identify the enriched cell types, candidate causal variants and genes, and cell type-specific regulatory mechanism underlying GWAS loci. CONCLUSIONS: Overall, genetic effects on gene regulation are highly context dependent. Our results suggest that cell type-dependent genetic effect is driven by precise modulation of both trans-factor expression and chromatin accessibility of cis-elements. Our findings indicate hierarchical collaboration among transcription factors plays a crucial role in mediating cell type-specific effects of genetic variants on gene regulation.