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Frontiers in Cellular and Infection... 2024Dual-specificity LAMMER kinases are highly evolutionarily conserved in eukaryotes and play pivotal roles in diverse physiological processes, such as growth,...
Dual-specificity LAMMER kinases are highly evolutionarily conserved in eukaryotes and play pivotal roles in diverse physiological processes, such as growth, differentiation, and stress responses. Although the functions of LAMMER kinase in fungal pathogens in pathogenicity and stress responses have been characterized, its role in , a human fungal pathogen and a model yeast of basidiomycetes, remains elusive. In this study, we identified a homologous gene and constructed a strain with a deleted and a complemented strain. Similar to other fungi, the Δ mutant showed intrinsic growth defects. We observed that Lkh1 was involved in diverse stress responses, including oxidative stress and cell wall stress. Particularly, Lkh1 regulates DNA damage responses in Rad53-dependent and -independent manners. Furthermore, the absence of reduced basidiospore formation. Our observations indicate that Lkh1 becomes hyperphosphorylated upon treatment with rapamycin, a TOR protein inhibitor. Notably, deletion led to defects in melanin synthesis and capsule formation. Furthermore, we found that the deletion of led to the avirulence of in a systemic cryptococcosis murine model. Taken together, Lkh1 is required for the stress response, sexual differentiation, and virulence of .
Topics: Animals; Female; Humans; Mice; Cell Wall; Cryptococcosis; Cryptococcus neoformans; Disease Models, Animal; DNA Damage; Fungal Capsules; Fungal Proteins; Gene Deletion; Gene Expression Regulation, Fungal; Melanins; Mice, Inbred BALB C; Oxidative Stress; Phosphorylation; Sirolimus; Spores, Fungal; Stress, Physiological; Virulence
PubMed: 38774630
DOI: 10.3389/fcimb.2024.1369301 -
Heliyon May 2024The focus on reducing organic solvent usage, owing to their negative environmental and health impacts, is driving a search for innovative green alternative solvents in...
The focus on reducing organic solvent usage, owing to their negative environmental and health impacts, is driving a search for innovative green alternative solvents in academia and industry. Blume (CH) exhibits many therapeutic activities, including antioxidant and anti-inflammatory efficacy. The objective of this study is to evaluate the optimal solvent concentration using a simplex-lattice design with an aqueous-polyols mixture and to optimize the parameters for extracting bioactive compounds and antioxidant activities from ultrasound-assisted extraction (UAE) of CH leaves through central composite design (CCD) in response surface methodology (RSM). This study examines the total phenolic content (TPC), antioxidant activities, comparison of different extraction conditions, identification of bioactive compounds, cell cytotoxicity, cellular antioxidant activity, and melanin content reduction efficacy of the extracts. According to the findings from the simplex-lattice model, the ideal solvent composition consisted of 32.57%w/w butylene glycol, 32.92%w/w glycerine, and 34.51%w/w water. Furthermore, based on the response model, optimal extraction conditions were identified as a 15-min extraction time and a solvent-to-sample ratio of 32.94:1. In comparison to alternative extraction methods, ultrasonic-assisted extraction using the aqueous-glycerine-butylene glycol (GB-UAE) extract resulted in notably elevated TPC and antioxidant responses (p < 0.05). Major antioxidant bioactive compounds included 4-(Butoxymethyl) phenol, 3--Caffeoyl-4--methylquinic acid, Quercetin 3-(2G-glucosylrutinoside), 2,4-Dihydroxybenzoic acid and other bioactive compounds. The GB-UAE extract revealed greater cell viability than UAE using ethanol (EtOH-UAE) extract in both cytotoxicity and cellular antioxidant assays at the same concentration. Additionally, it exhibited comparable melanin content reduction efficacy at a higher concentration compared to that of EtOH-UAE extract. The researcher anticipates that the current study will advance the utilization of an aqueous-polyols system for extracting bioactive compounds extending beyond CH leaves. Although the potential applications of CH leaves in cosmetics and pharmaceutical formulations have been identified, further comprehensive mechanistic and clinical studies are required to fully understand their effects.
PubMed: 38774328
DOI: 10.1016/j.heliyon.2024.e31150 -
Nature Communications May 2024Fossil feathers have transformed our understanding of integumentary evolution in vertebrates. The evolution of feathers is associated with novel skin ultrastructures,...
Fossil feathers have transformed our understanding of integumentary evolution in vertebrates. The evolution of feathers is associated with novel skin ultrastructures, but the fossil record of these changes is poor and thus the critical transition from scaled to feathered skin is poorly understood. Here we shed light on this issue using preserved skin in the non-avian feathered dinosaur Psittacosaurus. Skin in the non-feathered, scaled torso is three-dimensionally replicated in silica and preserves epidermal layers, corneocytes and melanosomes. The morphology of the preserved stratum corneum is consistent with an original composition rich in corneous beta proteins, rather than (alpha-) keratins as in the feathered skin of birds. The stratum corneum is relatively thin in the ventral torso compared to extant quadrupedal reptiles, reflecting a reduced demand for mechanical protection in an elevated bipedal stance. The distribution of the melanosomes in the fossil skin is consistent with melanin-based colouration in extant crocodilians. Collectively, the fossil evidence supports partitioning of skin development in Psittacosaurus: a reptile-type condition in non-feathered regions and an avian-like condition in feathered regions. Retention of reptile-type skin in non-feathered regions would have ensured essential skin functions during the early, experimental stages of feather evolution.
Topics: Animals; Feathers; Dinosaurs; Fossils; Biological Evolution; Skin; Reptiles; Melanosomes; Animal Scales; Epidermis; beta-Keratins
PubMed: 38773066
DOI: 10.1038/s41467-024-48400-3 -
Clinical Case Reports May 2024In extradigital glomus tumors, (1) noncontact and (2) contact dermoscopy show (1) a central purplish-white area corresponding to tumor nests surrounding enlarged...
In extradigital glomus tumors, (1) noncontact and (2) contact dermoscopy show (1) a central purplish-white area corresponding to tumor nests surrounding enlarged vessels, a peripheral yellow-white area corresponding to mucin deposition, melanin granules, and fibrous tissue, and (2) white reticular and linear cord areas corresponding to pseudocapsules and collagen fibers.
PubMed: 38770410
DOI: 10.1002/ccr3.8907 -
Photoacoustics Aug 2024Psoriasis is a chronic inflammatory skin disease, characterized by thick scaly plaques. It imposes a notable disease burden with varying levels of severity affecting the...
Psoriasis is a chronic inflammatory skin disease, characterized by thick scaly plaques. It imposes a notable disease burden with varying levels of severity affecting the quality of life significantly. Current disease severity assessment relies on semi-objective visual inspection based on the Psoriasis Area and Severity index (PASI) score that might not be sensitive to sub-clinical changes. Histology of psoriasis skin lesions necessitate invasive skin biopsies. This indicates an unmet need for a non-invasive, objective and quantitative approach to assess disease severity serially. Herein, we employ multispectral Raster-Scanning Optoacoustic Mesoscopy (ms-RSOM) derived structural and microvascular functional imaging metrics to examine the lesional and non-lesional skin in psoriasis subjects across different severities and also evaluate the treatment outcome in a subject with topical steroids and biologics, such as adalimumab. ms-RSOM derived structural metrics like epidermal thickness and total blood volume (TBV) and microvascular functional information such as oxygen saturation (sO) are evaluated by spectrally resolving the endogenous chromophores like melanin, oxy-, and deoxy-hemoglobin. Initial findings reveal an elevated sO and TBV with severity in lesional and non-lesional psoriasis skin, thus representing increasing inflammation. An increase in epidermal thickness is also noted with the degree of severity, corresponding to the inflammation and increased abnormal cell growth. As a marker to evaluate the treatment response, we observed a decrease in epidermal thickness, sO and TBV in a psoriasis patient post-treatment, which is consistent with the decrease in the PASI score from 4.1 to 1.9. We envision that ms-RSOM has a huge potential to be translated into routine clinical setting for the diagnosis of severity and assessment of treatment monitoring in psoriasis subjects.
PubMed: 38764522
DOI: 10.1016/j.pacs.2024.100611 -
BMC Biology May 2024Verticillium wilt, caused by the fungus Verticillium dahliae, is a soil-borne vascular fungal disease, which has caused great losses to cotton yield and quality...
BACKGROUND
Verticillium wilt, caused by the fungus Verticillium dahliae, is a soil-borne vascular fungal disease, which has caused great losses to cotton yield and quality worldwide. The strain KRS010 was isolated from the seed of Verticillium wilt-resistant Gossypium hirsutum cultivar "Zhongzhimian No. 2."
RESULTS
The strain KRS010 has a broad-spectrum antifungal activity to various pathogenic fungi as Verticillium dahliae, Botrytis cinerea, Fusarium spp., Colletotrichum spp., and Magnaporthe oryzae, of which the inhibition rate of V. dahliae mycelial growth was 73.97% and 84.39% respectively through confrontation test and volatile organic compounds (VOCs) treatments. The strain was identified as Bacillus altitudinis by phylogenetic analysis based on complete genome sequences, and the strain physio-biochemical characteristics were detected, including growth-promoting ability and active enzymes. Moreover, the control efficiency of KRS010 against Verticillium wilt of cotton was 93.59%. After treatment with KRS010 culture, the biomass of V. dahliae was reduced. The biomass of V. dahliae in the control group (Vd991 alone) was 30.76-folds higher than that in the treatment group (KRS010+Vd991). From a molecular biological aspect, KRS010 could trigger plant immunity by inducing systemic resistance (ISR) activated by salicylic acid (SA) and jasmonic acid (JA) signaling pathways. Its extracellular metabolites and VOCs inhibited the melanin biosynthesis of V. dahliae. In addition, KRS010 had been characterized as the ability to promote plant growth.
CONCLUSIONS
This study indicated that B. altitudinis KRS010 is a beneficial microbe with a potential for controlling Verticillium wilt of cotton, as well as promoting plant growth.
Topics: Plant Diseases; Bacillus; Gossypium; Ascomycota; Verticillium; Phylogeny; Biological Control Agents
PubMed: 38764012
DOI: 10.1186/s12915-024-01913-1 -
Investigative Ophthalmology & Visual... May 2024To demonstrate the first near-infrared adaptive optics fluorescence lifetime imaging ophthalmoscopy (NIR-AOFLIO) measurements in vivo of the human retinal pigment...
PURPOSE
To demonstrate the first near-infrared adaptive optics fluorescence lifetime imaging ophthalmoscopy (NIR-AOFLIO) measurements in vivo of the human retinal pigment epithelial (RPE) cellular mosaic and to visualize lifetime changes at different retinal eccentricities.
METHODS
NIR reflectance and autofluorescence were captured using a custom adaptive optics scanning light ophthalmoscope in 10 healthy subjects (23-64 years old) at seven eccentricities and in two eyes with retinal abnormalities. Repeatability was assessed across two visits up to 8 weeks apart. Endogenous retinal fluorophores and hydrophobic whole retinal extracts of Abca4-/- pigmented and albino mice were imaged to probe the fluorescence origin of NIR-AOFLIO.
RESULTS
The RPE mosaic was resolved at all locations in five of seven younger subjects (<35 years old). The mean lifetime across near-peripheral regions (8° and 12°) was longer compared to near-foveal regions (0° and 2°). Repeatability across two visits showed moderate to excellent correlation (intraclass correlation: 0.88 [τm], 0.75 [τ1], 0.65 [τ2], 0.98 [a1]). The mean lifetime across drusen-containing eyes was longer than in age-matched healthy eyes. Fluorescence was observed in only the extracts from pigmented Abca4-/- mouse.
CONCLUSIONS
NIR-AOFLIO was repeatable and allowed visualization of the RPE cellular mosaic. An observed signal in only the pigmented mouse extract infers the fluorescence signal originates predominantly from melanin. Variations observed across the retina with intermediate age-related macular degeneration suggest NIR-AOFLIO may act as a functional measure of a biomarker for in vivo monitoring of early alterations in retinal health.
Topics: Humans; Retinal Pigment Epithelium; Ophthalmoscopy; Adult; Middle Aged; Animals; Female; Mice; Male; Young Adult; Optical Imaging; Reproducibility of Results; Infrared Rays; ATP-Binding Cassette Transporters; Fluorescein Angiography
PubMed: 38758638
DOI: 10.1167/iovs.65.5.27 -
Dermatology and Therapy Jun 2024Vitiligo is a chronic autoimmune disease characterized by destruction of melanocytes, leading to skin depigmentation. Vitiligo can have a high quality-of-life burden and...
INTRODUCTION
Vitiligo is a chronic autoimmune disease characterized by destruction of melanocytes, leading to skin depigmentation. Vitiligo can have a high quality-of-life burden and profound impact on psychosocial well-being. The objectives of this study were to describe the self-reported patient burden among patients with nonsegmental vitiligo with ≤ 10% affected body surface area, summarize the physician-reported psychosocial and psychological impact of vitiligo on patient lives, and describe disease characteristics and treatment history, goals, and satisfaction.
METHODS
Data were drawn from the Adelphi Vitiligo Disease Specific Programme™, a real-world, cross-sectional survey with retrospective data collection of physicians and patients with vitiligo, collected in the United States between October 2021 and April 2022. Separate surveys for dermatologists and patients contained questions on clinical and demographic characteristics of patients with vitiligo and burden of vitiligo. Treatment history, goals, and satisfaction were assessed together with the impact of vitiligo on quality of life.
RESULTS
Sixty-one dermatologists provided data for 326 patients with ≤ 10% affected body surface area (adults, n = 221; adolescents, n = 105); 90 of those patients also responded to the survey. The most common treatments were topical corticosteroids, topical calcineurin inhibitors, and narrow-band ultraviolet-B phototherapy, with the main treatment goal being repigmentation. Physician-reported treatment satisfaction was 56%; 25% of patients reported frustration with treatment options. Physicians reported impact of vitiligo on everyday life in 46% of patients. Patients reported 12.7% overall work impairment; mean scores for Hospital Anxiety and Depression Scale anxiety and depression domains were 3.5 and 2.2, respectively, and mean Vitiligo-specific Quality of Life index score was 26.9. Patients with facial involvement experienced higher burden than those without.
CONCLUSION
A high patient burden was reported by dermatologists and their patients with vitiligo who had ≤ 10% affected body surface area, including psychosocial and psychological consequences. These findings highlight an unmet need in the treatment of vitiligo.
PubMed: 38753072
DOI: 10.1007/s13555-024-01165-5 -
Cureus Apr 2024Background Gingival pigmentation (GP), characterized by the presence of melanin in the gingival tissues, is a common aesthetic concern in dental practice. While it poses...
Background Gingival pigmentation (GP), characterized by the presence of melanin in the gingival tissues, is a common aesthetic concern in dental practice. While it poses no inherent health risks, the visible discoloration may cause psychological distress for individuals seeking optimal dental aesthetics. Understanding the efficacy of various methods is essential for refining treatment strategies and enhancing patient satisfaction in the realm of gingival depigmentation (GD). Aim The objective of the study was to compare the effectiveness of scalpel and microneedling (MN) with ascorbic acid in the treatment of GD. Materials and methods Sixteen patients who had a complaint of GP were included in the study, of whom eight were allocated for depigmentation with a scalpel, and the other eight patients were treated with the MN technique with ascorbic acid. Postoperative wound healing scores were evaluated on the first and seventh days, respectively. The intensity of depigmentation was assessed at baseline, in the first month, and at the end of the third month, respectively. Results The mean Dummett-Gupta Oral Pigmentation Index (DOPI) score at baseline was 2.65±0.16 and 2.61±0.17 in the surgical and microneedling groups with ascorbic acid, respectively. The mean DOPI score at the end of the third month was 1.67±0.39 and 0.87±0.17 in the scalpel and MN with ascorbic acid groups, respectively. There was a statistically significant difference between the scalpel and MN with ascorbic acid groups at the end of the first and third months, respectively, where MN with ascorbic acid showed aesthetically pleasing outcomes. Patients treated with the scalpel technique showed incomplete healing and ulceration on the first and seventh days after the procedure when compared to the MN technique with ascorbic acid. The healing index scores were statistically significant in the MN with ascorbic acid group. Conclusion The MN technique with ascorbic acid is a successful technique for treating GD. It showed aesthetically gratifying outcomes when compared to the conventional surgical technique.
PubMed: 38752063
DOI: 10.7759/cureus.58285 -
Frontiers in Endocrinology 2024The brain regulates multiple physiological processes in fish. Despite this, knowledge about the basic structure and function of distinct brain regions in non-model fish...
The brain regulates multiple physiological processes in fish. Despite this, knowledge about the basic structure and function of distinct brain regions in non-model fish species remains limited due to their diversity and the scarcity of common biomarkers. In the present study, four major brain parts, the telencephalon, diencephalon, mesencephalon and rhombencephalon, were isolated in largemouth bass, . Within these parts, nine brain regions and 74 nuclei were further identified through morphological and cytoarchitectonic analysis. Transcriptome analysis revealed a total of 7153 region-highly expressed genes and 176 region-specifically expressed genes. Genes related to growth, reproduction, emotion, learning, and memory were significantly overexpressed in the olfactory bulb and telencephalon (OBT). Feeding and stress-related genes were in the hypothalamus (Hy). Visual system-related genes were predominantly enriched in the optic tectum (OT), while vision and hearing-related genes were widely expressed in the cerebellum (Ce) region. Sensory input and motor output-related genes were in the medulla oblongata (Mo). Osmoregulation, stress response, sleep/wake cycles, and reproduction-related genes were highly expressed in the remaining brain (RB). Three candidate marker genes were further identified for each brain regions, such as neuropeptide FF () for OBT, pro-melanin-concentrating hormone () for Hy, vesicular inhibitory amino acid transporter () for OT, excitatory amino acid transporter 1 () for Ce, peripherin () for Mo, and isotocin neurophysin () for RB. Additionally, the distribution of seven neurotransmitter-type neurons and five types of non-neuronal cells across different brain regions were analyzed by examining the expression of their marker genes. Notably, marker genes for glutamatergic and GABAergic neurons showed the highest expression levels across all brain regions. Similarly, the marker gene for radial astrocytes exhibited high expression compared to other markers, while those for microglia were the least expressed. Overall, our results provide a comprehensive overview of the structural and functional characteristics of distinct brain regions in the largemouth bass, which offers a valuable resource for understanding the role of central nervous system in regulating physiological processes in teleost.
Topics: Animals; Bass; Biomarkers; Brain; Neurons; Gene Expression Profiling; Transcriptome; Telencephalon
PubMed: 38745953
DOI: 10.3389/fendo.2024.1385575