Search Results (17)

Cuticular wax plays an important role in the quality of kumquat (Fortunella crassifolia Swingle) fruit. In this study, the wax morphology, compositional profile of epi- and intracuticular wax, and crucial gene expression in ‘Rongan’ kumquat (RAK) and ‘Huapi’ kumquat (HPK) were analyzed during fruit development. The results showed that the surfaces of two kumquat fruits were covered with an amorphous wax layer containing a small number of platelets. Compared to RAK, HPK contained more abundant and larger wax crystals during fruit development. In two kumquat fruits, the epicuticular wax and its major compositions consistently displayed significantly higher levels than the intracuticular wax. Additionally, their main wax composition shifted from alkanes in the early developmental stages to triterpenoids at harvest in both layers, while aldehydes were specifically enriched in the epicuticular wax. During the fruit development from 90 to 180 DAF, HPK fruit exhibited significantly higher levels of epicuticular wax and its majority fractions than RAK fruit. Meanwhile, the intracuticular wax contents of HPK from 90 DAF to 150 DAF were significantly higher than those in RAK, with triterpenoids accounting for the largest proportion of this increase. qRT-PCR results indicated that the up-regulation of wax-related genes in HPK was linked to its increased epicuticular wax deposition during the development. Overall, this study provided a comprehensive overview of the morphology, composition, and biosynthesis of cuticular wax in kumquat fruit during development. Full article

The two-component system HPK₆/RRP₆ related to the pln locus of plantaricin biosynthesis was screened out. The overexpression of LuxR-type regulator RRP₆ promoted the transcription of ABC transporter-related genes, thereby increasing plantaricin EF yield. Its yield in 163(rrp₆) reached 16.01 mg/L, which was 1.20-fold that of the original strain. The regulatory mechanism indicated that RRP₆ could bind to two sites of the plnG1 promoter, promoting its transcription and translation, accelerating the secretion of plantaricin and auto-inducing peptide, and enhancing the extracellular plantaricin yield. Amino acids Q73, R144, T171, and Y175 play a crucial role in the binding of RRP₆. Furthermore, potential regulatory compensation within the Lactiplantibacillus plantarum 163 genome may compensate for the negative effects after the deletion of rrp₆. These results provide a novel strategy for increasing plantaricin EF yield, which facilitates its large-scale application as a natural and safe food preservative in agriculture and the food industry. Full article

This article presents the results of a comprehensive material analysis of medieval decorative bands from two different excavations in present-day Poland, specifically from early medieval cemeteries in Gródek upon the Bug River and Pień. The bands are complex materials composed of various fibres and precious metals, dyed with natural dyes using recipes that are often unknown today. They represent rare archaeological finds, challenging to analyse not only due to the complexity of their structure and materials but also because of significant deterioration caused by exposure to environmental conditions and harmful substances present in the burial soil. Optical microscopy and scanning electron microscopy (SEM) facilitated the identification of raw materials, manufacturing techniques, and ornamentation. SEM coupled with energy-dispersive X-ray spectroscopy (EDS) was employed to analyse the metal threads, determine their elemental composition, and assess their preservation state. Natural dye identification was performed on selected objects using high-performance liquid chromatography combined with spectrophotometric detectors and tandem mass spectrometry with electrospray ionization (HPLC-UV-Vis-ESI-MS/MS). The analysis of these results enabled drawing conclusions regarding the origin of the bands and their manufacturing methods. The dating of the bands, based on ornamentation and manufacturing techniques, was confirmed by radiocarbon dating, indicating they date back to the 10th–12th centuries. They were produced using two weaving techniques, a narrow haberdashery loom and a tablet loom, primarily from silk and metal threads—silver and silver-gilt. Some materials consisted of red-dyed silk (using kermes or madder), including a metal thread core. The analysis also provided valuable insights into textile degradation, particularly the corrosion mechanisms affecting the metal threads. Full article

Hematopoietic progenitor kinase 1 (HPK1), a negative regulator of T-cells, B-cells, and dendritic cells, has gained attention in antitumor immunotherapy research over the past decade. No HPK1 inhibitor has yet reached clinical approval, largely due to selectivity and drug-like limitations. Leveraging the available structural insights into HPK1, we conducted a rational hit identification using a structure-based virtual screening of over 600,000 drug-like molecules from ASINEX and OTAVA databases. A series of molecular docking studies, in vitro kinase assays, and molecular dynamics simulations were conducted to identify viable HPK1 inhibitor hits. This approach resulted in two promising novel hit scaffolds, 4H-Pyrido[1,2-a] thieno[2,3-d] pyrimidin-4-one (ISR-05) and quinolin-2(1H)-one (ISR-03), neither of which has previously been reported as an HPK1 inhibitor. ISR-05 and ISR-03 exhibited IC₅₀ values of 24.2 ± 5.07 and 43.9 ± 0.134 µM, respectively, in kinase inhibition assays. These hits constitute tractable starting points for future hit-to-lead optimization aimed at developing more effective HPK1 inhibitors for cancer therapy. Full article

Helicobacter pylori is a pathogenic bacterium that causes gastric and extragastric diseases. We have previously demonstrated that one of the mechanisms of H. pylori-associated chronic immune thrombocytopenia involves immune complexes of platelets, a H. pylori protein Lpp20 and an anti-Lpp20 antibody. However, it remains unclear how Lpp20 enters the body. We hypothesize that bacterial extracellular vesicles (bEVs) transport Lpp20. Thus, this study assessed Lpp20 in the bEVs released from seven clinical H. pylori isolates, using immunoprecipitation (IP), immunoblotting (IB), and surface plasmon resonance imaging (SPRi), with anti-GroEL (a marker of bEVs) and anti-Lpp20 antibodies. Lpp20 and bEVs were each detected in lysates of all seven strains. IP–IB experiments demonstrated that bEVs containing Lpp20 were produced by five of the strains (J99, SS1, HPK5, JSHR3, and JSHR31). SPRi using an anti-Lpp20 antibody demonstrated significantly higher reflectance from the strain HPK5 than from its lpp20-disrupted strains (p < 0.01), indicating localization of Lpp20 on the bEVs’ surface; Lpp20 may also be contained within bEVs. The bEVs containing Lpp20 were not detected from two clinical H. pylori strains (26695 and JSHR6) or from two lpp20-disrupted strains (26695ΔLpp20 and HPK5ΔLpp20). Differences in Lpp20 detection in bEVs are likely due to variations in bEV production resulting from strain diversity. Full article

The main consequence of radiation damage on a silicon photomultiplier (SiPM) is a significant increase in the dark current. If the SiPM is not adequately cooled, the power dissipation causes it to heat up, which alters its performance parameters. To investigate this heating effect, a measurement cycle was developed and performed with a KETEK SiPM glued to an Al₂O₃ substrate and with HPK SiPMs glued to either an Al₂O₃ substrate or a flexible PCB. The assemblies were connected either directly to a temperature-controlled chuck on a probe station, or through layers of materials with defined thermal resistance. An LED operated in DC mode was used to illuminate the SiPM and to tune the power dissipated in a measurement cycle. The SiPM current was used to determine the steady-state temperature reached by the SiPM via a calibration curve. The increase in SiPM temperature due to self-heating is analyzed as a function of the power dissipation in the SiPM and the thermal resistance. This information can be used to adjust the operating voltage of the SiPMs, taking into account the effects of self-heating. Similarly, this approach can be applied to investigate the unknown thermal contact of packaged SiPMs. Full article

The finite number of pixels in a silicon photomultiplier (SiPM) limits its dynamic range to light pulses up to typically 80% of the total number of pixels in a device. Correcting the non-linear response is essential to extend the SiPM’s dynamic range. One challenge in determining the non-linear response correction is providing a reference linear light source. Instead, the single-step method used to calibrate PMTs is applied, based on the difference in responses to two light sources. With this method, the response of an HPK SiPM (S14160-1315PS) is corrected to linearity within 5% while extending the linear dynamic range by a factor larger than ten. The study shows that the response function does not vary by more than 5% for a variation in the operating voltage between 2 and 5 V overvoltage in the gate length between 20 and 100 ns and for a time delay between the primary and secondary light of up to 40 ns. Full article

Hematopoietic progenitor kinase 1 (HPK1) is a negative regulator of T cell receptor, which has been regarded as a potential target for immunotherapy. Yu et al. observed the off-target effect of the high-throughput screening HPK1 kinase inhibitor hits on JAK1 kinase. The off-target effect is usually due to the lack of specificity of the drug, resulting in toxic side effects. Therefore, exploring the mechanisms to selectively inhibit HPK1 is critical for developing effective and safe inhibitors. In this study, two indazole compounds as HPK1 inhibitors with different selectivity towards JAK1 were used to investigate the selectivity mechanism using multiple computational methods, including conventional molecular dynamics simulations, binding free energy calculations and umbrella sampling simulations. The results indicate that the salt bridge between the inhibitor and residue Asp101 of HPK1 favors their selectivity towards HPK1 over JAK1. Information obtained from this study can be used to discover and design more potent and selective HPK1 inhibitors for immunotherapy. Full article

Activated microglia are involved in secondary injury after acute spinal cord injury (SCI) and in development of spinal cord-related neuropathic pain (NeP). The aim of the study was to assess expression of translocator protein 18 kDa (TSPO) as an indicator of microglial activation and to investigate visualization of the dynamics of activated microglia in the injured spinal cord using PET imaging with (R)-[¹¹C]PK11195, a specific ligand for TSPO. In SCI chimeric animal models, TSPO was expressed mainly in activated microglia. Accumulation of (R)-[³H]PK11195 was confirmed in autoradiography and its dynamics in the injured spinal cord were visualized by (R)-[¹¹C]PK11195 PET imaging in the acute phase after SCI. In clinical application of (R)-[¹¹C]PK11195 PET/MRI of the cervical spinal cord in patients with NeP related to cervical disorders, uptake was found in cases up to 10 months after injury or surgery. No uptake could be visualized in the injured spinal cord in patients with chronic NeP at more than 1 year after injury or surgery, regardless of the degree of NeP. However, a positive correlation was found between standardized uptake value ratio and the severity of NeP, suggesting the potential of clinical application for objective evaluation of chronic NeP. Full article

Progressive degeneration of dopaminergic neurons, immune activation, and α-synuclein pathology characterize Parkinson’s disease (PD). We previously reported that unilateral intranigral injection of recombinant adeno-associated viral (rAAV) vectors encoding wild-type human α-synuclein produced a rat model of early PD with dopamine terminal dysfunction. Here we tested the hypothesis that decreases in dopamine result in increased postsynaptic dopamine D2/D3 receptor expression, neuroinflammation, and reduced synaptic vesicle glycoprotein 2A (SV2A) density. Rats were injected with rAAV encoding α-synuclein or green fluorescent protein and subjected to non-pharmacological motor tests, before euthanization at 12 weeks post-injection. We performed: (1) in situ hybridization of nigral tyrosine hydroxylase mRNA, (2) HPLC of striatal dopamine content, and (3) autoradiography with [³H]raclopride, [³H]DTBZ, [³H]GBR12935, [³H]PK11195, and [³H]UCB-J to measure binding at D2/3 receptors, vesicular monoamine transporter 2, dopamine transporters, mitochondrial translocator protein, and SV2A, respectively. rAAV-α-synuclein induced motor asymmetry and reduced tyrosine hydroxylase mRNA and dopamine content in ipsilateral brain regions. This was paralleled by elevated ipsilateral postsynaptic dopamine D2/3 receptor expression and immune activation, with no changes to synaptic SV2A density. In conclusion, α-synuclein overexpression results in dopaminergic degeneration that induced compensatory increases in D2/3 binding and immune activation, recapitulating many of the pathological characteristics of PD. Full article

In this paper, we report on the photon emission of Silicon Photomultipliers (SiPMs) from avalanche pulses generated in dark conditions, with the main objective of better understanding the associated systematics for next-generation, large area, SiPM-based physics experiments. A new apparatus for spectral and imaging analysis was developed at TRIUMF and used to measure the light emitted by the two SiPMs considered as photo-sensor candidates for the nEXO neutrinoless double-beta decay experiment: one Fondazione Bruno Kessler (FBK) VUV-HD Low Field (LF) Low After Pulse (Low AP) (VUV-HD3) SiPM and one Hamamatsu Photonics K.K. (HPK) VUV4 Multi-Pixel Photon Counter (MPPC). Spectral measurements of their light emissions were taken with varying over-voltage in the wavelength range of 450–1020 nm. For the FBK VUV-HD3, at an over-voltage of $12.1\pm 1.0$ V, we measured a secondary photon yield (number of photons ($\gamma$) emitted per charge carrier ($e^{-}$)) of $(4.04\pm 0.02)\times {10}^{-6}$$\gamma /e^{-}$. The emission spectrum of the FBK VUV-HD3 contains an interference pattern consistent with thin-film interference. Additionally, emission microscopy images (EMMIs) of the FBK VUV-HD3 show a small number of highly localized regions with increased light intensity (hotspots) randomly distributed over the SiPM surface area. For the HPK VUV4 MPPC, at an over-voltage of $10.7\pm 1.0$ V, we measured a secondary photon yield of $(8.71\pm 0.04)\times {10}^{-6}$$\gamma /e^{-}$. In contrast to the FBK VUV-HD3, the emission spectra of the HPK VUV4 did not show an interference pattern—likely due to a thinner surface coating. The EMMIs of the HPK VUV4 also revealed a larger number of hotspots compared to the FBK VUV-HD3, especially in one of the corners of the device. The photon yield reported in this paper may be limited if compared with the one reported in previous studies due to the measurement wavelength range, which is only up to 1020 nm. Full article

Traditionally, the special function theory has many applications in various areas of mathematical physics, economics, statistics, engineering, and many other branches of science. Inspired by certain recent extensions of the k-analogue of gamma, the Pochhammer symbol, and hypergeometric functions, this work is devoted to the study of the k-analogue of Gauss hypergeometric functions by the Hadamard product. We give a definition of the Hadamard product of k-Gauss hypergeometric functions (HPkGHF) associated with the fourth numerator and two denominator parameters. In addition, convergence properties are derived from this function. We also discuss interesting properties such as derivative formulae, integral representations, and integral transforms including beta transform and Laplace transform. Furthermore, we investigate some contiguous function relations and differential equations connecting the HPkGHF. The current results are more general than previous ones. Moreover, the proposed results are useful in the theory of k-special functions where the hypergeometric function naturally occurs. Full article

Gentiana lutea is a bitter herb that is traditionally used to improve gastric disorders. Recently, we have shown that Gentiana lutea extract (GE) also modulates the lipid metabolism of human keratinocytes in vitro and in vivo. In the present study, we investigated the role of GE on ceramide synthesis in human primary keratinocytes (HPKs) and psoriasis-like keratinocytes. We could demonstrate that GE increased the concentrations of glucosylceramides and the ceramide AS/AdS subclass without affecting the overall ceramide content in HPKs. The expression of ceramide synthase 3 (CERS3) and elongases (ELOVL1 and 4) was reduced in psoriasis lesions compared to healthy skin. Psoriasis-like HPKs, generated by stimulating HPKs with cytokines that are involved in the pathogenesis of psoriasis (IL-17, TNF-α, IL-22 and IFN-γ) showed increased levels of IL-6, IL-8 and increased expression of DEFB4A, as well as decreased expression of ELOVL4. The treatment with GE partly rescued the reduced expression of ELOVL4 in psoriasis-like HPKs and augmented CERS3 expression. This study has shown that GE modulates ceramide synthesis in keratinocytes. Therefore, GE might be a novel topical treatment for skin diseases with an altered lipid composition such as psoriasis. Full article

T cells play a critical role in the pathogenesis of systemic lupus erythematosus (SLE), which is a severe autoimmune disease. In the past 60 years, only one new therapeutic agent with limited efficacy has been approved for SLE treatment; therefore, the development of early diagnostic biomarkers and therapeutic targets for SLE is desirable. Mitogen-activated protein kinase kinase kinase kinases (MAP4Ks) and dual-specificity phosphatases (DUSPs) are regulators of MAP kinases. Several MAP4Ks and DUSPs are involved in T-cell signaling and autoimmune responses. HPK1 (MAP4K1), DUSP22 (JKAP), and DUSP14 are negative regulators of T-cell activation. Consistently, HPK1 and DUSP22 are downregulated in the T cells of human SLE patients. In contrast, MAP4K3 (GLK) is a positive regulator of T-cell signaling and T-cell-mediated immune responses. MAP4K3 overexpression-induced RORγt–AhR complex specifically controls interleukin 17A (IL-17A) production in T cells, leading to autoimmune responses. Consistently, MAP4K3 and the RORγt–AhR complex are overexpressed in the T cells of human SLE patients, as are DUSP4 and DUSP23. In addition, DUSPs are also involved in either human autoimmune diseases (DUSP2, DUSP7, DUSP10, and DUSP12) or T-cell activation (DUSP1, DUSP5, and DUSP14). In this review, we summarize the MAP4Ks and DUSPs that are potential biomarkers and/or therapeutic targets for SLE. Full article

In this study, isotropic pitch-based carbon fibers were prepared from a mixture of petroleum residue and graphene nanoplatelets with different contents. The softening point and synthetic yield of synthesized isotropic pitches were analyzed and compared to characterize the nature of the pitches. The surface and thermal characteristics of the fibers were observed using scanning electron microscopy and thermogravimetric analysis (TGA), respectively. From the results, it was observed that the prepared carbon fibers had an interesting core-shell structure. In the TGA analysis with air, the carbon fiber having 0.1 wt.% of graphene showed a higher residue yield than that of the sample having 1.0 wt.% of graphene. This result can be explained due to the graphene being placed on the surface region of the carbon fibers and directly helping to increase the surface area of the carbon fibers, resulting in rapid oxidation due to the enhanced contact area with oxygen. Full article