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The Journal of Biological Chemistry Apr 2024Bathy phytochromes are a subclass of bacterial biliprotein photoreceptors that carry a biliverdin IXα chromophore. In contrast to prototypical phytochromes that adopt a...
Bathy phytochromes are a subclass of bacterial biliprotein photoreceptors that carry a biliverdin IXα chromophore. In contrast to prototypical phytochromes that adopt a red-light-absorbing Pr ground state, the far-red light-absorbing Pfr-form is the thermally stable ground state of bathy phytochromes. Although the photobiology of bacterial phytochromes has been extensively studied since their discovery in the late 1990s, our understanding of the signal transduction process to the connected transmitter domains, which are often histidine kinases, remains insufficient. Initiated by the analysis of the bathy phytochrome PaBphP from Pseudomonas aeruginosa, we performed a systematic analysis of five different bathy phytochromes with the aim to derive a general statement on the correlation of photostate and autokinase output. While all proteins adopt different Pr/Pfr-fractions in response to red, blue, and far-red light, only darkness leads to a pure or highly enriched Pfr-form, directly correlated with the lowest level of autokinase activity. Using this information, we developed a method to quantitatively correlate the autokinase activity of phytochrome samples with well-defined stationary Pr/Pfr-fractions. We demonstrate that the off-state of the phytochromes is the Pfr-form and that different Pr/Pfr-fractions enable the organisms to fine-tune their kinase output in response to a certain light environment. Furthermore, the output response is regulated by the rate of dark reversion, which differs significantly from 5 s to 50 min half-life. Overall, our study indicates that bathy phytochromes function as sensors of light and darkness, rather than red and far-red light, as originally postulated.
Topics: Bacterial Proteins; Darkness; Histidine Kinase; Light; Photoreceptors, Microbial; Phytochrome; Pseudomonas aeruginosa; Enzyme Activation
PubMed: 38462162
DOI: 10.1016/j.jbc.2024.107148 -
Science Advances Feb 2024is a unique cyanobacterium using chlorophyll (Chl ) as its major pigment and thus can use far-red light for photosynthesis. Photosystem II (PSII) of associates with a...
is a unique cyanobacterium using chlorophyll (Chl ) as its major pigment and thus can use far-red light for photosynthesis. Photosystem II (PSII) of associates with a number of prochlorophyte Chl-binding (Pcb) proteins to act as the light-harvesting system. We report here the cryo-electron microscopic structure of a PSII-Pcb megacomplex from at a 3.6-angstrom overall resolution and a 3.3-angstrom local resolution. The megacomplex is organized as a tetramer consisting of two PSII core dimers flanked by sixteen symmetrically related Pcb proteins, with a total molecular weight of 1.9 megadaltons. The structure reveals the detailed organization of PSII core consisting of 15 known protein subunits and an unknown subunit, the assembly of 4 Pcb antennas within each PSII monomer, and possible pathways of energy transfer within the megacomplex, providing deep insights into energy transfer and dissipation mechanisms within the PSII-Pcb megacomplex involved in far-red light utilization.
Topics: Photosystem II Protein Complex; Prochlorophytes; Chlorophyll; Photosynthesis
PubMed: 38394197
DOI: 10.1126/sciadv.adk7140 -
Acta Dermato-venereologica Feb 2024Acne in adult females is triggered mainly by hormones. Doxycycline is a reference treatment in acne. Spironolactone targets the androgen receptor of sebaceous glands and... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy of Spironolactone Compared with Doxycycline in Moderate Acne in Adult Females: Results of the Multicentre, Controlled, Randomized, Double-blind Prospective and Parallel Female Acne Spironolactone vs doxyCycline Efficacy (FASCE) Study.
Acne in adult females is triggered mainly by hormones. Doxycycline is a reference treatment in acne. Spironolactone targets the androgen receptor of sebaceous glands and is prescribed off-label for female adult acne. This multicentre, controlled, randomized, double-blind prospective and parallel study assessed the efficacy of spironolactone compared with doxycycline in adult female acne. A total of 133 women with moderate acne were randomized to receive treatment with: (i) doxycycline and benzoyl peroxide for 3 months followed by a 3-month treatment with its placebo and benzoyl peroxide, or (ii) spironolactone and benzoyl peroxide for 6 months. Successfully treated patients continued with benzoyl peroxide or spironolactone alone for a further 6 months. Primary endpoints were treatment success at month 4 and month 6 with the AFAST score. At all visits, the ECLA score, lesion counts, local and systemic safety and quality of life were assessed. Spironolactone performed better at month 4 and showed a statistically significant better treatment success after 6 months than doxycycline (p = 0.007). Spironolactone was 1.37-times and 2.87-times more successful compared with doxycycline at respective time-points. AFAST and ECLA scores, as well as lesion counts always improved more with spironolactone. Patients' quality of life was better with spironolactone at month 4 and month 6. Spironolactone was very well tolerated. This is the first study to show that, in female adults with moderate acne, treatment with spironolactone is significantly more successful than doxycycline and very well tolerated.
Topics: Adult; Humans; Female; Doxycycline; Spironolactone; Quality of Life; Prospective Studies; Acne Vulgaris; Benzoyl Peroxide; Treatment Outcome; Double-Blind Method
PubMed: 38380975
DOI: 10.2340/actadv.v104.26002 -
ACS Omega Feb 2024The restoration process of burned and rough skin takes a long time and remains a critical challenge. It can be repaired through a combination of proper care, hydration,...
The restoration process of burned and rough skin takes a long time and remains a critical challenge. It can be repaired through a combination of proper care, hydration, and topical therapies. In this study, a novel nanoemulsion was synthesized through the high-energy ultrasonication method. A total of five nanoemulsions (NE1-5) were prepared with varying concentrations of sandalwood oil, a nonionic surfactant (polysorbate 80), and water. Among them, NE3 had a number of appropriate physicochemical characteristics, such as physiological pH (5.58 ± 0.09), refractive index (∼1.34), electrical conductivity (115 ± 0.23 mS cm), and transmittance (∼96.5%), which were suitable for skin care applications. The NE3 had a strong surface potential of -18.5 ± 0.15 mV and a hydrodynamic size of 61.99 ± 0.22 nm with a polydispersity index of 0.204. The structural integrity and a distinct droplet size range between 50 and 100 nm were confirmed by transmission electron microscopic analysis. The skin regeneration and restoration abilities of synthesized nanoemulsions were examined by conducting an in vivo study on Sprague-Dawley rats. Exposure to NE3 significantly increased the healing process in burned skin as compared to untreated control and nonemulsified sandalwood oil. In another set of experiments, the NE3-treated rough skin became softer, smoother, and less scaly than all other treatments. Enhanced fatty acids, i.e., palmitic acid, stearic acid, and cholesterol, were recorded in NE3-supplemented burned and rough skin compared to the untreated control. The NE3 had outstanding compatibility with key components of skincare products without any stability issues. Its biocompatibility with the cellular system was established by the negligible generation of reactive oxygen species (ROS) and a lack of genotoxicity. Considering these results, NE3 can be used in cosmetic products such as creams, lotions, and serums, allowing industries to achieve improved product formulations and provide better healthcare benefits to humanity.
PubMed: 38371762
DOI: 10.1021/acsomega.3c03811 -
Molecular Medicine (Cambridge, Mass.) Feb 2024Scleral extracellular matrix (ECM) remodeling plays a crucial role in the development of myopia, particularly in ocular axial elongation. Thrombospondin-1 (THBS1), also...
BACKGROUND
Scleral extracellular matrix (ECM) remodeling plays a crucial role in the development of myopia, particularly in ocular axial elongation. Thrombospondin-1 (THBS1), also known as TSP-1, is a significant cellular protein involved in matrix remodeling in various tissues. However, the specific role of THBS1 in myopia development remains unclear.
METHOD
We employed the HumanNet database to predict genes related to myopic sclera remodeling, followed by screening and visualization of the predicted genes using bioinformatics tools. To investigate the potential target gene Thbs1, we utilized lens-induced myopia models in male C57BL/6J mice and performed Western blot analysis to detect the expression level of scleral THBS1 during myopia development. Additionally, we evaluated the effects of scleral THBS1 knockdown on myopia development through AAV sub-Tenon's injection. The refractive status and axial length were measured using a refractometer and SD-OCT system.
RESULTS
During lens-induced myopia, THBS1 protein expression in the sclera was downregulated, particularly in the early stages of myopia induction. Moreover, the mice in the THBS1 knockdown group exhibited alterations in myopia development in both refraction and axial length changed compared to the control group. Western blotting analysis confirmed the effectiveness of AAV-mediated knockdown, demonstrating a decrease in COLA1 expression and an increase in MMP9 levels in the sclera.
CONCLUSION
Our findings indicate that sclera THBS1 levels decreased during myopia development and subsequent THBS1 knockdown showed a decrease in scleral COLA1 expression. Taken together, these results suggest that THBS1 plays a role in maintaining the homeostasis of scleral extracellular matrix, and the reduction of THBS1 may promote the remodeling process and then affect ocular axial elongation during myopia progression.
Topics: Animals; Male; Mice; Disease Models, Animal; Mice, Inbred C57BL; Myopia; Sclera; Thrombospondin 1
PubMed: 38355399
DOI: 10.1186/s10020-024-00795-x -
Communications Biology Feb 2024The mesophilic purple sulfur phototrophic bacterium Allochromatium (Alc.) vinosum (bacterial family Chromatiaceae) has been a favored model for studies of bacterial...
The mesophilic purple sulfur phototrophic bacterium Allochromatium (Alc.) vinosum (bacterial family Chromatiaceae) has been a favored model for studies of bacterial photosynthesis and sulfur metabolism, and its core light-harvesting (LH1) complex has been a focus of numerous studies of photosynthetic light reactions. However, despite intense efforts, no high-resolution structure and thorough biochemical analysis of the Alc. vinosum LH1 complex have been reported. Here we present cryo-EM structures of the Alc. vinosum LH1 complex associated with reaction center (RC) at 2.24 Å resolution. The overall structure of the Alc. vinosum LH1 resembles that of its moderately thermophilic relative Alc. tepidum in that it contains multiple pigment-binding α- and β-polypeptides. Unexpectedly, however, six Ca ions were identified in the Alc. vinosum LH1 bound to certain α1/β1- or α1/β3-polypeptides through a different Ca-binding motif from that seen in Alc. tepidum and other Chromatiaceae that contain Ca-bound LH1 complexes. Two water molecules were identified as additional Ca-coordinating ligands. Based on these results, we reexamined biochemical and spectroscopic properties of the Alc. vinosum LH1-RC. While modest but distinct effects of Ca were detected in the absorption spectrum of the Alc. vinosum LH1 complex, a marked decrease in thermostability of its LH1-RC complex was observed upon removal of Ca. The presence of Ca in the photocomplex of Alc. vinosum suggests that Ca-binding to LH1 complexes may be a common adaptation in species of Chromatiaceae for conferring spectral and thermal flexibility on this key component of their photosynthetic machinery.
Topics: Light-Harvesting Protein Complexes; Chromatiaceae; Photosynthesis; Peptides
PubMed: 38347078
DOI: 10.1038/s42003-024-05863-w -
Photodiagnosis and Photodynamic Therapy Apr 2024Cutaneous leishmaniasis is a neglected disease prevalent in tropical countries, and conventional treatment can cause several serious side effects. Photodynamic therapy...
Cutaneous leishmaniasis is a neglected disease prevalent in tropical countries, and conventional treatment can cause several serious side effects. Photodynamic therapy (PDT) can be considered a promising treatment alternative, as it is non-invasive therapy that has no side effects and uses accessible and low-cost substances, such as curcumin. This study evaluated the PDT response with cationic and anionic BSA nanoparticles encapsulated with curcumin in macrophages infected with L. braziliensis, L. major, and L. amazonensis. The nanoparticle system was characterized using a steady-state technique, scanning electron microscopy (SEM) study, and its biological activity was evaluated using macrophage cell lines infected with different Leishmania species. All spectroscopy measurements demonstrated that BSA curcumin (BSACur) has good photophysical properties, and confocal microscopy shows that macrophages and protozoa internalized the nanoparticles. The viability test demonstrated that at low concentrations, such as 0.1, 0.7, and 1.0 µmol. L, there was a decrease in cell viability after PDT application. Furthermore, a decrease in the number of parasites recovered was observed in the PDT groups. The results allowed us to conclude that curcumin loaded into BSA nanoparticles may have potential application in drug delivery systems for PDT protocols, demonstrating reduced cell viability at lower concentrations than free curcumin.
Topics: Curcumin; Photochemotherapy; Photosensitizing Agents; Serum Albumin, Bovine; Nanoparticles; Animals; Cell Survival; Leishmania braziliensis; Mice; Cations; Leishmaniasis, Cutaneous; Leishmania major; Macrophages
PubMed: 38342387
DOI: 10.1016/j.pdpdt.2024.104001 -
Plant Biotechnology Journal Jul 2024In maize, two pyruvate orthophosphate dikinase (PPDK) regulatory proteins, ZmPDRP1 and ZmPDRP2, are respectively specific to the chloroplast of mesophyll cells (MCs) and...
The C4 photosynthesis bifunctional enzymes, PDRPs, of maize are co-opted to cytoplasmic viral replication complexes to promote infection of a prevalent potyvirus sugarcane mosaic virus.
In maize, two pyruvate orthophosphate dikinase (PPDK) regulatory proteins, ZmPDRP1 and ZmPDRP2, are respectively specific to the chloroplast of mesophyll cells (MCs) and bundle sheath cells (BSCs). Functionally, ZmPDRP1/2 catalyse both phosphorylation/inactivation and dephosphorylation/activation of ZmPPDK, which is implicated as a major rate-limiting enzyme in C4 photosynthesis of maize. Our study here showed that maize plants lacking ZmPDRP1 or silencing of ZmPDRP1/2 confer resistance to a prevalent potyvirus sugarcane mosaic virus (SCMV). We verified that the C-terminal domain (CTD) of ZmPDRP1 plays a key role in promoting viral infection while independent of enzyme activity. Intriguingly, ZmPDRP1 and ZmPDRP2 re-localize to cytoplasmic viral replication complexes (VRCs) following SCMV infection. We identified that SCMV-encoded cytoplasmic inclusions protein CI targets directly ZmPDRP1 or ZmPDRP2 or their CTDs, leading to their re-localization to cytoplasmic VRCs. Moreover, we found that CI could be degraded by the 26S proteasome system, while ZmPDRP1 and ZmPDRP2 could up-regulate the accumulation level of CI through their CTDs by a yet unknown mechanism. Most importantly, with genetic, cell biological and biochemical approaches, we provide evidence that BSCs-specific ZmPDRP2 could accumulate in MCs of Zmpdrp1 knockout (KO) lines, revealing a unique regulatory mechanism crossing different cell types to maintain balanced ZmPPDK phosphorylation, thereby to keep maize normal growth. Together, our findings uncover the genetic link of the two cell-specific maize PDRPs, both of which are co-opted to VRCs to promote viral protein accumulation for robust virus infection.
Topics: Potyvirus; Zea mays; Virus Replication; Plant Proteins; Plant Diseases; Photosynthesis; Pyruvate, Orthophosphate Dikinase; Chloroplasts
PubMed: 38339894
DOI: 10.1111/pbi.14304 -
JID Innovations : Skin Science From... Mar 2024Recent studies have provided information about digital eye strain and the potential damage that blue light from digital devices can cause to the eyes. In this study, we...
Recent studies have provided information about digital eye strain and the potential damage that blue light from digital devices can cause to the eyes. In this study, we analyzed the influence of blue light exposure on reconstructed 3-dimensional skin model using RNA sequencing to identify the expression of transcripts and abnormal events. Three-dimensional skin was exposed to visible light spectrum and isolated blue wavelength for 1, 2, and 4 hours to represent acute exposure and 1 hour over 4 sequential days to represent repeated exposure, respectively, in this in vitro model. We compared gene expression levels with those of unexposed control. Samples submitted to repeated exposure showed reduced and , whereas they showed increased gene expression, revealing a significantly negative impact. RT-PCR validation assay with exposed 3-dimensional skin compared with unexposed control regarding 1 and 4 days of incubation showed increased IL-6 signaling mechanism activation and signal transducer and activator of transcription 3 gene gene expression, whereas it showed decreased peroxisome proliferator-activated receptor signaling mechanism activation, suggesting an influence on inflammatory pathways. We also demonstrate upregulated gene expression of , , and in samples from exposed condition, corroborating previous findings related to pigmentation signaling stimuli. These results reveal, to our knowledge, previously unreported data that enable studies on molecular response correlation of in vitro digital blue light exposure and human skin studies.
PubMed: 38328595
DOI: 10.1016/j.xjidi.2023.100252 -
Actas Dermo-sifiliograficas Apr 2024
Topics: Humans; Dermatitis, Atopic; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Hepatitis C; Treatment Outcome; Severity of Illness Index
PubMed: 38325544
DOI: 10.1016/j.ad.2024.02.003