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1.
Heliyon ; 10(9): e30293, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38737239

ABSTRACT

Objective: To determine if dermoscopy, a technique widely utilized in dermatology for improved diagnosis of skin lesions, can be used comfortably for evaluating periorbital, eyelid, and conjunctival lesions. Design: Proof-of-concept study in which a technique for performing dermoscopy near the eye was developed, related educational material was prepared, and a protocol for dermoscopic image capture was created. Methods: Technicians used the developed materials to learn to take high-quality pictures with a 10x dermoscope attached to a standard cell phone camera. The images were assessed for diagnostic utility by an oculoplastic surgeon and two dermatologists. Participants: 115 patients recruited from ophthalmology clinics from July 2021 to April 2023 were photographed, yielding 129 lesions with high-quality dermoscopic images as assessed by an oculoplastic surgeon and two dermatologists. Results: Technicians reported a significant increase in confidence (measured on a 1-10 scale) with dermoscopy after training (pre-instruction mean = 1.72, median = 1, mode = 1, IQR = 1.25 vs mean = 7.69, median = 7.75, mode = 7 and 8, IQR = 1.5 post-instruction. Wilcoxon rank sum test with continuity correction, W = 0, p < 0.001, paired t = 13.95, p < 0.0001). Incorporating a contact plate with a 4 × 4mm reticule on the dermoscope aided in photographing ocular and periocular lesions. Conclusion: Medical support staff in eye-care offices can be taught to use dermoscopes to capture high-quality images of periorbital, eyelid, and conjunctival lesions. Dermoscopy illuminates diagnostic features of lesions and thus offers a new avenue to improve decision-making in ophthalmology. Dermoscopy can be incorporated into telemedicine evaluations by ophthalmologists, oculoplastic surgeons, or affiliated dermatologists for triage of or rendering advice to patients and for planning of surgery if needed.

2.
medRxiv ; 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38496401

ABSTRACT

Individuals with schizophrenia suffer from higher morbidity and mortality throughout life partly due to acceleration of aging-related diseases and conditions. Systemic inflammation is a hallmark of aging and is also observed in schizophrenia. An improved understanding of how inflammation and accelerated aging contribute to long-term health outcomes in schizophrenia could provide more effective treatments to preserve long-term cognitive and physical function. In this pilot cross-sectional study, 24 older adults (≥55 years old) with schizophrenia were assessed on symptoms (Positive and Negative Syndrome Scale), neurocognition (Matrics Consensus Cognitive Battery), mobility (Timed Get Up and Go), and general health (SF-12). Serum levels of 112 different cytokines were measured, from which we derived estimated senescence-associated secretory phenotype (SASP) scores for each participant. Two-tailed Pearson's bivariate correlations were computed to test the associations between schizophrenia clinical outcomes with individual cytokines, and SASP. Higher levels of eotaxin, IL-1α, IL-1ß, and IFNα are associated with both worse PANSS negative and depressive symptoms scores. IL-1α and IL-1ß negatively associated with general physical health whereas eotaxin negatively associated with mobility and global cognition. Overall, we found that specific inflammatory cytokines, but not composite measurements of SASP, are associated with clinical outcomes in older adults with schizophrenia.

3.
Biol Psychiatry ; 2024 Jan 18.
Article in English | MEDLINE | ID: mdl-38244753

ABSTRACT

BACKGROUND: A key challenge in developing treatments for neuropsychiatric illness is the disconnect between preclinical models and the complexity of human social behavior. We integrate voluntary social self-administration into a rodent model of social stress as a platform for the identification of fundamental brain and behavior mechanisms underlying stress-induced individual differences in social motivation. METHODS: Here, we introduced an operant social stress procedure in male and female mice composed of 3 phases: 1) social self-administration training, 2) social stress exposure concurrent with reinforced self-administration testing, and 3) poststress operant testing under nonreinforced and reinforced conditions. We used social-defeat and witness-defeat stress in male and female mice. RESULTS: Social defeat attenuated social reward seeking in males but not females, whereas witness defeat had no effect in males but promoted seeking behavior in females. We resolved social stress-induced changes to social motivation by aggregating z-scored operant metrics into a cumulative social index score to describe the spectrum of individual differences exhibited during operant social stress. Clustering does not adequately describe the relative distributions of social motivation following stress and is better described as a nonbinary behavioral distribution defined by the social index score, capturing a dynamic range of stress-related alterations in social motivation inclusive of sex as a biological variable. CONCLUSIONS: We demonstrated that operant social stress can detect stable individual differences in stress-induced changes to social motivation. The inclusion of volitional behavior in social procedures may enhance the understanding of behavioral adaptations that promote stress resiliency and their mechanisms under more naturalistic conditions.

4.
J Fish Biol ; 104(3): 517-535, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37984834

ABSTRACT

Determining how environmental conditions contribute to divergence among populations and drive speciation is fundamental to resolving mechanisms and understanding outcomes in evolutionary biology. Postglacial freshwater fish species in the Northern Hemisphere are ideal biological systems to explore the effects of environment on diversification in morphology, ecology, and genetics (ecomorph divergences) within lakes. To date, various environmental factors have been implicated in the presence of multiple ecomorphs within particular lakes or regions. However, concerted evidence for generalizable patterns in environmental variables associated with speciation across geographical regions and across species and genera has been lacking. Here, we aimed to identify key biotic and abiotic factors associated with ecological divergence of postglacial freshwater fish species into multiple sympatric ecomorphs, focusing on species in the well-studied, widespread, and co-distributed genera Gasterosteus, Salvelinus, and Coregonus (stickleback, charr, and whitefish, respectively). We found that the presence of multiple sympatric ecomorphs tended to be associated with increasing lake surface area, maximum depth, and nutrient availability. In addition, predation, competition, and prey availability were suggested to play a role in divergence into multiple ecomorphs, but the effects of biotic factors require further study. Although we identified several environmental factors correlated with the presence of multiple ecomorphs, there were substantial data gaps across species and regions. An improved understanding of these systems may provide insight into both generalizable environmental factors involved in speciation in other systems, and potential ecological and evolutionary responses of species complexes when these variables are altered by environmental change.


Subject(s)
Salmonidae , Smegmamorpha , Animals , Biological Evolution , Trout , Lakes , Genetic Speciation
5.
Neurosurg Rev ; 47(1): 16, 2023 Dec 19.
Article in English | MEDLINE | ID: mdl-38110768

ABSTRACT

The mastoid foramen (MF) is located on the mastoid process of the temporal bone, adjacent to the occipitomastoid suture or the parietomastoid suture, and contains the mastoid emissary vein (MEV). In retrosigmoid craniotomy, the MEV has been used to localize the position of the sigmoid sinus and, thus, the placement of the initial burr hole. Therefore, this study aimed to examine the exact location and variants of the MF and MEV to determine if their use in localizing the sigmoid sinus is reasonable. The sample in this study comprised 22 adult dried skulls (44 sides). MF were identified and classified into five types based on location, prevalence, whether they communicated with the sigmoid sinus and exact entrance into the groove of the sigmoid sinus. The diameters and relative locations of the MF in the skull were measured and recorded. Finally, the skulls were drilled to investigate the course of the MEV. Additionally, ten latex-injected sides from human cadavers were also dissected to follow the MEV, especially in cases with more than one vein. We found that type I MFs (single foramen) were the most prevalent (50%). These MFs were mainly located on the occipitomastoid suture; only one case on the right side was adjacent to the parietomastoid suture. Type II (paired foramina) was the second most prevalent (22.73%), followed by type III (13.64%), type 0 (9.09%), and type IV (4.55%). The diameter of the external opening in a connecting MF (2.43 ± 0.79) was twice that of a non-connecting MF (1.14 ± 0.56). Interestingly, on one side, two MFs on the external surface shared a single internal opening; the MEV bifurcated. MFs followed three different courses: ascending, almost horizontal, and descending. Regardless of how many external openings there were for the MF, these all ended at a single opening in the groove for the sigmoid sinus. For cadaveric specimens with multiple MEVs, all terminated in the sigmoid sinus as a single vein, with the more medial veins terminating more medially into the sinus. Based on our study, the MF/MEV can guide the surgeon and help localize the deeper-lying sigmoid sinus. Knowledge of this anatomical relationship could be an adjunct to neuronavigational technologies.


Subject(s)
Mastoid , Skull , Adult , Humans , Mastoid/surgery , Skull/surgery , Cranial Sinuses/surgery , Craniotomy , Jugular Veins/surgery
6.
Polymers (Basel) ; 15(19)2023 Sep 29.
Article in English | MEDLINE | ID: mdl-37835999

ABSTRACT

Due to its chemical structure and the resulting dielectric properties, the processing of the commonly used particle foam material, expanded polypropylene (ePP), is limited. Processing within the radio-frequency welding process is therefore only possible with the use of processing aids. In this paper, a new approach for the use of a solid and dielectric heatable coating for the production of three-dimensional welded components out of ePP is presented. For this purpose, three different types of water-soluble polymer polyvinyl alcohol (PVA) were analyzed as potential coating materials. The thermal and dielectric properties of the coating were further adjusted by a modification with glycerol. The maximum amount of glycerol tested was 25% by volume. It influences both the temperature development in the radio-frequency (RF) welding process as well as the adhesive bond between the ePP foam particles. It is shown that the 120 °C approach in the RF welding process resulted in a cohesive bond between the coating layers. In this way, bonded plates can be produced. In mechanical tests with compression of 20%, the manufactured plates show sufficient load capacity. Furthermore, it can be shown that a separation of PVA and ePP by type, and thereby a separation of the foam particles, is possible with the use of hot water. This might open a new way for recycling of particle foams.

7.
Plant J ; 116(4): 974-988, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37818860

ABSTRACT

In modern reproducible, hypothesis-driven plant research, scientists are increasingly relying on research data management (RDM) services and infrastructures to streamline the processes of collecting, processing, sharing, and archiving research data. FAIR (i.e., findable, accessible, interoperable, and reusable) research data play a pivotal role in enabling the integration of interdisciplinary knowledge and facilitating the comparison and synthesis of a wide range of analytical findings. The PLANTdataHUB offers a solution that realizes RDM of scientific (meta)data as evolving collections of files in a directory - yielding FAIR digital objects called ARCs - with tools that enable scientists to plan, communicate, collaborate, publish, and reuse data on the same platform while gaining continuous quality control insights. The centralized platform is scalable from personal use to global communities and provides advanced federation capabilities for institutions that prefer to host their own satellite instances. This approach borrows many concepts from software development and adapts them to fit the challenges of the field of modern plant science undergoing digital transformation. The PLANTdataHUB supports researchers in each stage of a scientific project with adaptable continuous quality control insights, from the early planning phase to data publication. The central live instance of PLANTdataHUB is accessible at (https://git.nfdi4plants.org), and it will continue to evolve as a community-driven and dynamic resource that serves the needs of contemporary plant science.


Subject(s)
Databases as Topic , Information Dissemination , Plants
8.
Nat Food ; 4(9): 746-750, 2023 09.
Article in English | MEDLINE | ID: mdl-37735511

ABSTRACT

Recent studies have estimated the potential yield impacts of pesticide reductions in the European Union. While these estimates guide policy design, they are often based on worst-case assumptions and rarely account for positive ecological feedbacks that would contribute to sustainable crop yields in the long term.


Subject(s)
Food , Pesticides , Europe , European Union , Policy
9.
Immunol Rev ; 319(1): 142-150, 2023 10.
Article in English | MEDLINE | ID: mdl-37507355

ABSTRACT

Rheumatoid arthritis (RA) is a chronic inflammatory disease of the synovial joints that affects ~1% of the human population. Joint swelling and bone erosion, hallmarks of RA, contribute to disability and, sometimes, loss of life. Mechanistically, disease is driven by immune dysregulation characterized by circulating autoantibodies, inflammatory mediators, tissue degradative enzymes, and metabolic dysfunction of resident stromal and recruited immune cells. Cell death by apoptosis has been therapeutically explored in animal models of RA due to the comparisons drawn between synovial hyperplasia and paucity of apoptosis in RA with the malignant transformation of cancer cells. Several efforts to induce cell death have shown benefits in reducing the development and/or severity of the disease. Apoptotic cells are cleared by phagocytes in a process known as efferocytosis, which differs from microbial phagocytosis in its "immuno-silent," or anti-inflammatory, nature. Failures in efferocytosis have been linked to autoimmune disease, whereas administration of apoptotic cells in RA models effectively inhibits inflammatory indices, likely though efferocytosis-mediated resolution-promoting mechanisms. However, the nature of signaling pathways elicited and the molecular identity of clearance mediators in RA are understudied. Furthermore, canonical efferocytosis machinery elements also play important non-canonical functions in homeostasis and pathology. Here, we discuss the roles of efferocytosis machinery components in models of RA and discuss their potential involvement in disease pathophysiology.


Subject(s)
Arthritis, Rheumatoid , Autoimmune Diseases , Animals , Humans , Phagocytosis , Phagocytes , Apoptosis
10.
Trends Biotechnol ; 41(8): 1027-1040, 2023 08.
Article in English | MEDLINE | ID: mdl-37419837

ABSTRACT

Significant shares of harvests are lost to pests and diseases, therefore, minimizing these losses could solve part of the supply constraints to feed the world. Cisgenesis is defined as the insertion of genetic material into a recipient organism from a donor that is sexually compatible. Here, we review (i) conventional plant breeding, (ii) cisgenesis, (iii) current pesticide-based disease management, (iv) potential economic implications of cultivating cisgenic crops with durable disease resistances, and (v) potential environmental implications of cultivating such crops; focusing mostly on potatoes, but also apples, with resistances to Phytophthora infestans and Venturia inaequalis, respectively. Adopting cisgenic varieties could provide benefits to farmers and to the environment through lower pesticide use, thus contributing to the European Green Deal target.


Subject(s)
Disease Resistance , Pesticides , Plants, Genetically Modified/genetics , Disease Resistance/genetics , Plant Breeding , Crops, Agricultural/genetics
11.
Sci Rep ; 13(1): 3818, 2023 03 07.
Article in English | MEDLINE | ID: mdl-36882486

ABSTRACT

Diabetic retinopathy (DR) is the most common diabetic microvascular complication and cause of blindness in adults under the age of 65. Our results suggest that, when comparing transcriptomes of cultures grown in hypoxic conditions versus room-air, cybrids containing mitochondria from African and Asian diabetic subjects ([Afr + Asi]/DM) have some uniquely different transcriptome profiles compared to European/diabetic (Euro/DM) cybrids (e.g., fatty acid metabolism: EnrichR rank 10 in [Afr + Asi]/DM, rank 85 in Euro/DM; Endocytosis: rank 25 in [Afr + Asi]/DM, rank 5 in Euro/DM; Ubiquitin Mediated Proteolysis: rank 34 in [Afr + Asi]/DM, rank 7 in Euro/DM). As determined by both RNA-seq and qRT-PCR results, transcription of the gene encoding oleoyl-ACP hydrolase (OLAH) was significantly increased in [Afr + Asi]/DM cybrids compared to Euro/DM cybrids in hypoxic conditions. Additionally, our results show that in hypoxic conditions, Euro/DM cybrids and [Afr + Asi]/DM cybrids show similar decreases in ROS production. All cybrids showed decreased ZO1-minus protein levels, but their phagocytic functions were not significantly altered in hypoxic conditions. In conclusion, our findings suggest that the "molecular memory" imparted by [Afr + Asi]/DM mtDNA may act through one of the molecular pathways seen in transcriptome analysis, such as fatty acid metabolism, without significantly changing essential RPE functions.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Adult , Humans , Diabetic Retinopathy/genetics , Asian , Black People , Hypoxia/genetics , Fatty Acids , Diabetes Mellitus/genetics
12.
Nutrients ; 14(21)2022 Oct 25.
Article in English | MEDLINE | ID: mdl-36364734

ABSTRACT

Despite being largely preventable, cardiovascular disease (CVD) is still the leading cause of death globally. Recent studies suggest that the immune system, particularly a form of systemic chronic inflammation (SCI), is involved in the mechanisms leading to CVD; thus, targeting SCI may help prevent or delay the onset of CVD. In a recent placebo-controlled randomized clinical trial, an oat product providing 3 g of ß-Glucan improved cholesterol low-density lipoprotein (LDL) levels and lowered cardiovascular risk in adults with borderline high cholesterol. Here, we conducted a secondary measurement of the serum samples to test whether the oat product has the potential to reduce SCI and improve other clinical outcomes related to healthy aging. We investigated the effects of the oat product on a novel metric for SCI called Inflammatory Age® (iAge®), derived from the Stanford 1000 Immunomes Project. The iAge® predicts multimorbidity, frailty, immune decline, premature cardiovascular aging, and all-cause mortality on a personalized level. A beneficial effect of the oat product was observed in subjects with elevated levels of iAge® at baseline (>49.6 iAge® years) as early as two weeks post-treatment. The rice control group did not show any significant change in iAge®. Interestingly, the effects of the oat product on iAge® were largely driven by a decrease in the Eotaxin-1 protein, an aging-related chemokine, independent of a person's gender, body mass index, or chronological age. Thus, we describe a novel anti-SCI role for oats that could have a major impact on functional, preventative, and personalized medicine.


Subject(s)
Avena , Cardiovascular Diseases , Adult , Humans , Cholesterol, LDL , Cardiovascular Diseases/etiology , Dietary Fiber/analysis , Cholesterol , Edible Grain/chemistry , Inflammation/drug therapy
13.
FASEB Bioadv ; 4(10): 675-689, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36238361

ABSTRACT

Activation of the Simulator of Interferon Genes (STING) system by mitochondrial (mt) DNA can upregulate type 1 interferon genes and enhance immune responses to combat bacterial and viral infections. In cancers, the tumor-derived DNA activates STING leading to upregulation of IFN-beta and induction of antitumor T cells. The entire mtDNA from the cell lines was sequenced using next-generation sequencing (NGS) technology with independent sequencing of both strands in both directions, allowing identification of low-frequency heteroplasmy SNPs. There were 15 heteroplasmy SNPs showing a range from 3.4% to 40.5% occurrence in the K cybrid cell lines. Three H haplogroup cybrids possessed SNP heteroplasmy that ranged from 4.39% to 30.7%. The present study used qRT-PCR to determine if cybrids of H and K haplogroups differentially regulate expression levels of five cancer genes (BRAC1, ALK, PD1, EGFR, and HER2) and seven STING subunits genes (CGAS, TBK1, IRF3, IκBa, NFκB, TRAF2, and TNFRSF19). Some cybrids underwent siRNA knockdown of STING followed by qRT-PCR in order to determine the impact of STING on gene expression. Rho0 (lacking mtDNA) ARPE-19 cells were used to determine if mtDNA is required for the expression of the cancer genes studied. Our results showed that (a) K cybrids have lower expression levels for BRAC1, ALK, PD1, EGFR, IRF3, and TNFRSF19 genes but increased transcription for IκBa and NFκB compared to H cybrids; (b) STING KD decreases expression of EGFR in both H and K cybrids, and (c) PD1 expression is negligible in Rho0 cells. Our findings suggest that the STING DNA sensing pathway may be a previously unrecognized pathway to target modulation of cancer-related genes and the PD1 expression requires the presence of mtDNA.

14.
Front Syst Neurosci ; 16: 926388, 2022.
Article in English | MEDLINE | ID: mdl-35993086

ABSTRACT

In 2014, we participated in a special issue of Frontiers examining the neural processing of appetitive and aversive events. Specifically, we reviewed brain areas that contribute to the encoding of prediction errors and value versus salience, attention and motivation. Further, we described how we disambiguated these cognitive processes and their neural substrates by using paradigms that incorporate both appetitive and aversive stimuli. We described a circuit in which the orbitofrontal cortex (OFC) signals expected value and the basolateral amygdala (BLA) encodes the salience and valence of both appetitive and aversive events. This information is integrated by the nucleus accumbens (NAc) and dopaminergic (DA) signaling in order to generate prediction and prediction error signals, which guide decision-making and learning via the dorsal striatum (DS). Lastly, the anterior cingulate cortex (ACC) is monitoring actions and outcomes, and signals the need to engage attentional control in order to optimize behavioral output. Here, we expand upon this framework, and review our recent work in which within-task manipulations of both appetitive and aversive stimuli allow us to uncover the neural processes that contribute to the detection of outcomes delivered to a conspecific and behaviors in social contexts. Specifically, we discuss the involvement of single-unit firing in the ACC and DA signals in the NAc during the processing of appetitive and aversive events in both social and non-social contexts.

15.
Polymers (Basel) ; 14(14)2022 Jul 08.
Article in English | MEDLINE | ID: mdl-35890575

ABSTRACT

In recent years, the demand for polymer compound solutions for the application of bipolar plates in polymer electrolyte membrane fuel cells (PEMFC) has increased continuously due to significant cost and lifetime advantages compared to metallic solutions. The main challenge of the compounds is the high filler content required to ensure sufficient electrical conductivity of the bipolar plates. The associated increase in viscosity and simultaneously increased thermal conductivity limit the conventional injection molding process in terms of achievable flow path length to wall thickness ratios (plate aspect ratio). In order to evaluate the extent to which highly modified electrically conductive polymer material systems can be processed into thin-walled and highly dimensionally stable bipolar plates, an injection compression molding process with dynamic mold temperature control (ICM-DT) has been developed. For this purpose, a compound was prepared from polypropylene (PP) and graphite-flakes. The compound was characterized with respect to the achieved filler content, the electrical conductivity, as well as the pressure- and temperature-dependent solidification range. The ICM-DT experiments were carried out by varying the maximum mold temperature and the compression force. In addition, the process was designed with multiple compression and decompression steps to account for a possible pressure-dependent solidification of the compound. The plates were characterized with respect to the achieved plate aspect ratio and the flow-path-dependent dimensional thickness stability. It was shown that the plate aspect ratio could be increased by up to 125% with the maximum filler content compared to conventional injection molding processes provided in the literature. With the multi-stage ICM-DT process, it was also possible to optimize the thickness dimensional stability with a maximum deviation of 3% over the flow path.

16.
Polymers (Basel) ; 14(8)2022 Apr 15.
Article in English | MEDLINE | ID: mdl-35458364

ABSTRACT

Expandable graphite (EG) and graphite (G) were assessed as multifunctional additives improving both flame retardancy and thermal conductivity in highly filled, thermal conductive polymeric materials based on polyamide 6 (PA6). Fire testing was conducted using modern UL-94, LOI and cone calorimeter test setups. It is demonstrated that thermal conductivity can significantly influence the time to ignition, although offering little fire resistance once ignited even in highly filled systems. Thus, for PA6 formulations containing solely 70 wt.% G, the peak heat release rate (pHRR) measured in cone calorimeter tests was 193 kW/m², whereas PA6 formulations containing 20 wt.% EG/50 wt.% G did not exhibit a measurable heat development. Particular attention was paid to effect separation between thermal conductivity and residue formation. Good thermal conductivity properties are proven to be particularly effective in test scenarios where the heat impact is comparatively low and the testing environment provides good heat dissipation and convective cooling possibilities. For candle-like ignition scenarios (e.g., LOI), filling levels of >50 wt.% (G or EG/G) are shown to be sufficient to suppress ignition exclusively by thermal conductivity. V0 classifications in UL-94 vertical burning tests were achieved for PA6 formulations containing ≥70 wt.% G, ≥25 wt.% EG and ≥20 wt.% EG/25 wt.% G.

17.
Int J Med Inform ; 159: 104669, 2022 03.
Article in English | MEDLINE | ID: mdl-34979435

ABSTRACT

Colorectal cancer is one of the leading causes of cancer-related death, worldwide. Early detection of suspicious tissues can significantly improve the survival rate. In this study, the performance of a wide variety of deep learning-based architectures is evaluated for automatic tumor segmentation of colorectal tissue samples. The proposed approach highlights the utility of incorporating convolutional neural network modules and transfer learning in the encoder part of a segmentation architecture for histopathology image analysis. A comparative and extensive experiment was conducted on a challenging histopathological segmentation task to demonstrate the effectiveness of incorporating deep modules in the segmentation encoder-decoder network as well as the contributions of its components. Experimental results demonstrate that shared DenseNet and LinkNet architecture is promising, achieves the state-of-the-art performance, and outperforms other methods with a dice similarity index of 82.74%±1.77, accuracy of 87.07%±1.56, and f1-score value of 82.79%±1.79.


Subject(s)
Colorectal Neoplasms , Neural Networks, Computer , Colorectal Neoplasms/diagnosis , Humans , Image Processing, Computer-Assisted/methods , Machine Learning
19.
Exp Eye Res ; 214: 108857, 2022 01.
Article in English | MEDLINE | ID: mdl-34856207

ABSTRACT

Our goal was to explore the detrimental impacts of ciprofloxacin (CPFX) and tetracycline (TETRA) on human retinal Müller (MIO-M1) cells in vitro. Cells were exposed to 30, 60 and 120 µg/ml of CPFX and TETRA. The cellular metabolism was measured with the MTT assay. The JC-1 and CM-H2DCFDA assays were used to evaluate the levels of mitochondrial membrane potential (MMP) and ROS (reactive oxygen species), respectively. Mitochondrial DNA (mtDNA) copy number, along with gene expression levels associated with apoptotic (BAX, BCL2-L13, BCL2, CASP-3 and CASP-9), inflammatory (IL-6, IL-1ß, TGF-α, TGF-ß1 and TGF-ß2) and antioxidant pathways (SOD2, SOD3, GPX3 and NOX4) were analyzed via Quantitative Real-Time PCR (qRT-PCR). Bioenergetic profiles were measured using the Seahorse® XF Flux Analyzer. Cells exposed 24 h to 120 µg/ml TETRA demonstrated higher cellular metabolism compared to vehicle-treated cells. At each time points, (i) all TETRA concentrations reduced MMP levels and (ii) ROS levels were reduced by TETRA 120 µg/ml treatment. TETRA caused (i) higher expression of CASP-3, CASP-9, TGF-α, IL-1B, GPX3 and SOD3 but (ii) decreased levels of TGF-B2 and SOD2. ATP production and spare respiratory capacity declined with TETRA treatment. Cellular metabolism was reduced with CPFX 120 µg/ml in all cultures and 60 µg/ml after 72 h. The CPFX 120 µg/ml reduced MMP in all cultures and ROS levels (72 h). CPFX treatment (i) increased expression of CASP-3, CASP-9, and BCL2-L13, (ii) elevated the basal oxygen consumption rate, and (iii) lowered the mtDNA copy numbers and expression levels of TGF-B2, IL-6 and IL-1B compared to vehicle-control cells. We conclude that clinically relevant dosages of bactericidal and bacteriostatic antibiotics can have negative effects on the cellular metabolism and mitochondrial membrane potential of the retinal MIO-M1 cells in vitro. It is noteworthy to mention that apoptotic and inflammatory pathways in exposed cells were affected significantly This is the first study showing the negative impact of fluoroquinolones and tetracyclines on mitochondrial behavior of human retinal MIO-M1 cells.


Subject(s)
Anti-Bacterial Agents/pharmacology , Ciprofloxacin/pharmacology , Ependymoglial Cells/drug effects , Mitochondria/drug effects , Tetracycline/pharmacology , Apoptosis Regulatory Proteins/genetics , Cell Survival , Cells, Cultured , DNA Copy Number Variations , DNA, Mitochondrial/genetics , Ependymoglial Cells/metabolism , Humans , Interleukins/genetics , Membrane Potential, Mitochondrial/physiology , Mitochondria/metabolism , Oxidoreductases/genetics , RNA, Messenger/genetics , Reactive Oxygen Species/metabolism , Real-Time Polymerase Chain Reaction
20.
Proc Natl Acad Sci U S A ; 118(51)2021 12 21.
Article in English | MEDLINE | ID: mdl-34903645

ABSTRACT

Fisheries induce one of the strongest anthropogenic selective pressures on natural populations, but the genetic effects of fishing remain unclear. Crucially, we lack knowledge of how capture-associated selection and its interaction with reductions in population density caused by fishing can potentially shift which genes are under selection. Using experimental fish reared at two densities and repeatedly harvested by simulated trawling, we show consistent phenotypic selection on growth, metabolism, and social behavior regardless of density. However, the specific genes under selection-mainly related to brain function and neurogenesis-varied with the population density. This interaction between direct fishing selection and density could fundamentally alter the genomic responses to harvest. The evolutionary consequences of fishing are therefore likely context dependent, possibly varying as exploited populations decline. These results highlight the need to consider environmental factors when predicting effects of human-induced selection and evolution.


Subject(s)
Fisheries , Life History Traits , Selection, Genetic , Aggression , Animals , Energy Metabolism/genetics , Female , Genetic Association Studies , Genome , Male , Phenotype , Population Density , Zebrafish
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