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13 pages, 335 KB  
Article
Knowledge, Attitudes and Practices of Audiologists in India Towards Audiological Care of Individuals with Cognitive Impairments—A Preliminary Exploratory Study
by Dhanshree R. Gunjawate, Poorva Advait Patki, Twinkle Lijo Kirianthan and Rohit Ravi
Audiol. Res. 2026, 16(5), 121; https://doi.org/10.3390/audiolres16050121 - 23 Aug 2026
Viewed by 133
Abstract
Background/Objectives: The present study aimed to explore the knowledge, attitudes and practices of audiologists in India towards audiological care of individuals with cognitive impairments. Methods: The questionnaire was adapted from a previously published questionnaire designed to explore knowledge, attitude, and practices [...] Read more.
Background/Objectives: The present study aimed to explore the knowledge, attitudes and practices of audiologists in India towards audiological care of individuals with cognitive impairments. Methods: The questionnaire was adapted from a previously published questionnaire designed to explore knowledge, attitude, and practices regarding comorbid hearing loss and cognitive impairment among Australian allied hearing healthcare professionals. Participants included audiologists with at least a bachelor’s degree in audiology and speech-language pathology, a minimum of one year of work experience and registration with the Rehabilitation Council of India. An online questionnaire was created using Google Forms and disseminated via social media and personal emails. Continuous variables were summarized using means and standard deviation, while categorical variables were reported as frequencies and percentages. Results: A total of 140 audiologists participated in the study. Overall, the responses indicated a generally positive awareness towards managing individuals with comorbid hearing loss and cognitive impairment. Most respondents were mindful about the coexistence of hearing loss and cognitive impairment while working with older adults, with 74.3% either agreeing or strongly agreeing. This self-reported awareness was not consistently reflected in reported practice, with only 31.4% having used a formal cognitive screening test as part of their clinical practice. Conclusions: Overall, the findings suggest that while audiologists report a degree of self-perceived awareness regarding cognitive impairment, this does not consistently translate into practice. Notable gaps remain in training, awareness of appropriate screening tools, and actual implementation of cognitive screening, highlighting the need for greater clinical support, structured training, and clearer referral pathways to bridge the gap between self-reported awareness and evidence-based practice. Full article
(This article belongs to the Special Issue Hearing Loss and Cognition: New Frontiers)
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31 pages, 9145 KB  
Review
Yield Gaps in Major Crops of India: A Review of Drivers and Sustainable Intensification Pathways
by Prajwal Ghanshyam Dodewar, Ram Swaroop Bana, Yadunath Bajgai, Arpula Sairam, Pothula Srinivasa Brahmanand, Khajanchi Lal, Hide Omae, Twinkle Jena, Ch. Srinivasa Rao and Rattan Lal
Land 2026, 15(8), 1453; https://doi.org/10.3390/land15081453 - 12 Aug 2026
Viewed by 408
Abstract
India faces large, persistent yield gaps across eight major crops—wheat, rice, maize, soybean, pulses, mustard, cotton, and sugarcane—that collectively limit food security and rural income. This review synthesises evidence from over 100 peer-reviewed studies (1990–2024) to provide the first comprehensive, multi-crop, agro-climatically resolved [...] Read more.
India faces large, persistent yield gaps across eight major crops—wheat, rice, maize, soybean, pulses, mustard, cotton, and sugarcane—that collectively limit food security and rural income. This review synthesises evidence from over 100 peer-reviewed studies (1990–2024) to provide the first comprehensive, multi-crop, agro-climatically resolved yield gap analysis for India. Applying the three-tier framework of potential yield (Yp), attainable yield (Ya), and farmer yield (Yf), exploitable yield gaps are quantified at national and agro-climatic zone level, ranked limiting factors are identified, and projected climate change impacts are assessed. Yield gaps range from 20 to 35% in irrigated rice of the north-western Indo-Gangetic Plain to 60–75% in rainfed cotton and pulses of the semi-arid tropics. Yield gaps of blackgram across 20 major districts average 515 kg ha−1, driven by moisture stress, biotic pressure, and management constraints. Nitrogen management, irrigation access, variety adoption, and sowing-date optimisation collectively explain 80–85% of exploitable gaps, while nitrogen and irrigation alone account for 40–58%. Closing 50% of exploitable yield gaps could add approximately 100 million tonnes of food grain annually without expanding cultivated area, directly supporting Sustainable Development Goal (SDG 2). However, climate change is projected to widen yield gaps of rainfed rice by 15–30% by the 2040s under Representative Concentration Pathway (RCP) 8.5. Beyond this crop-by-crop synthesis, the review proposes a constraint-transition framework in which the dominant type of limiting factor shifts predictably from biophysical (water, climate) in the largest-gap rainfed systems to agronomic management (nitrogen, sowing date, variety) at intermediate gap levels and to institutional and socioeconomic constraints (credit, extension, land tenure, gender) as gaps narrow in the best-resourced irrigated systems, thus offering a conceptual lens for prioritising interventions by development stage rather than by crop alone. Full article
(This article belongs to the Special Issue Young Researchers in Land, Soil, and Water)
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16 pages, 2252 KB  
Article
Simple Blue LED-Excited Fluorescence and Chromaticity Measurements as Screening Indices for Avocado Ripeness
by Ichiro Tono, Makoto Saito, Fujio Terai, Yoshiro Baba and Hiroyasu Ishikawa
Int. J. Plant Biol. 2026, 17(7), 51; https://doi.org/10.3390/ijpb17070051 - 28 Jun 2026
Viewed by 307
Abstract
In response to the need for a simple, non-destructive method for evaluating avocado ripeness, we measured chlorophyll-related fluorescence and chromaticity of the outer skin using simple optical equipment and evaluated their relationship with whole-fruit compression (wfc), which was used as a firmness-based ripeness [...] Read more.
In response to the need for a simple, non-destructive method for evaluating avocado ripeness, we measured chlorophyll-related fluorescence and chromaticity of the outer skin using simple optical equipment and evaluated their relationship with whole-fruit compression (wfc), which was used as a firmness-based ripeness index. A compact system consisting of a blue LED excitation source and a small spectrometer was used to measure fluorescence spectra, and a commercially available colorimeter was used to evaluate chromaticity. Hass avocado samples purchased from multiple retail stores in Japan and stored for different periods were examined. The combination of the fluorescence intensity ratio I740/I685 and the lightness parameter L* showed a moderate correlation with wfc, with R2 = 0.48. The fluorescence ratio I740/I685 was treated not as a direct measure of chlorophyll content, but as a spectral index associated with ripening-related changes in avocado skin, including chlorophyll-related fluorescence and skin optical properties. These results suggest that the combination of simple blue LED-excited fluorescence and chromaticity measurements may be useful as a practical screening approach for roughly estimating avocado ripeness in commercially available fruit. Full article
(This article belongs to the Section Plant Physiology)
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24 pages, 289 KB  
Case Report
The Use of Research Findings on Self-Regulated Learning by Teachers and Students in an Australian High School
by Michael J. Lawson, Stella Vosniadou, Helen Stephenson, Lachlan McFarlane, Jason Loke, Tracy Robinson, Ben Cullen, Jess Rogers, Stew Nancarrow, Brenna Andrews, Nathan General, Twinkle Gomes, Sophie Calliss and Paige Harrison
Behav. Sci. 2025, 15(12), 1644; https://doi.org/10.3390/bs15121644 - 30 Nov 2025
Cited by 1 | Viewed by 946
Abstract
Reviews of the use of research ideas by teachers indicate that such use is less frequent than it could be. One area in which such a pattern of use is apparent concerns the effective promotion by teachers of strategies for the self-regulation of [...] Read more.
Reviews of the use of research ideas by teachers indicate that such use is less frequent than it could be. One area in which such a pattern of use is apparent concerns the effective promotion by teachers of strategies for the self-regulation of learning (SRL). Despite evidence of the importance of explicit SRL promotion, it is apparent that findings from research are not being used by many teachers. This report provides details of an instance of effective use of research findings by both teachers and students in one Australian secondary school following the involvement of a group of teachers from the school in a professional development program related to SRL and to the ICAP framework for cognitive engagement The report provides details of teacher-designed classroom interventions and activities of a student group which included use of the research findings with other students. From the research, two factors seen to have stimulated use of the research ideas emerge. The first is the contiguity of the professional development program and the actions of school leaders, teachers, and students. The second factor is the continuing involvement of researchers with teachers. The report provides an example of how students can engage in promotion of SRL strategies to other students. Full article
(This article belongs to the Special Issue The Promotion of Self-Regulated Learning (SRL) in the Classroom)
12 pages, 2253 KB  
Article
Enhancing Migraine Trigger Surprisal Predictions: A Bayesian Approach to Establishing Prospective Expectations
by Dana P. Turner, Emily Caplis, Twinkle Patel and Timothy T. Houle
Entropy 2025, 27(11), 1102; https://doi.org/10.3390/e27111102 - 25 Oct 2025
Viewed by 1200
Abstract
Prior work has demonstrated that higher surprisal, a measure quantifying the unexpectedness of a trigger exposure, predicts headache onset over 12 to 24 h. However, these analyses relied on retrospective expectations of trigger exposure formed after extended data collection. To operationalize surprisal prospectively, [...] Read more.
Prior work has demonstrated that higher surprisal, a measure quantifying the unexpectedness of a trigger exposure, predicts headache onset over 12 to 24 h. However, these analyses relied on retrospective expectations of trigger exposure formed after extended data collection. To operationalize surprisal prospectively, Bayesian methods could update expectations dynamically over time. The objective of this study was to extend the application of surprisal theory for predicting migraine attack risk by developing methods to estimate trigger variable likelihood in real time, under conditions of limited personal observation. In a prospective daily diary study of individuals with migraine (N = 104), data were collected over 28 days, including stress, sleep, and exercise exposures. Bayesian models were applied to estimate daily expectations for each variable under uninformative and empirical priors derived from the sample. Stress was modeled using a hurdle-Gamma distribution, sleep using discrete outcomes from a Normal distribution, and exercise using a Bernoulli distribution. Surprisal was calculated based on the predictive distribution at each time point and compared to static empirical surprisal values obtained after full data collection. Dynamic Bayesian surprisal values systematically differed from retrospective empirical estimates, particularly early in the observation period. Divergence was larger and more variable under uninformative priors but attenuated over time. Empirically informed priors produced more stable, lower-bias surprisal trajectories. Substantial individual variability was observed across exposure types, especially for exercise behavior. Prospective surprisal modeling is feasible but highly sensitive to prior specification, especially in sparse data contexts (e.g., a binary exposure). Incorporating empirical or individually informed priors may improve early model calibration, though individual learning remains essential. These methods offer a foundation for real-time headache forecasting and dynamic modeling of brain–environment interactions. Full article
(This article belongs to the Section Information Theory, Probability and Statistics)
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32 pages, 1092 KB  
Review
Mitochondrial DNA Replication and Disease: A Historical Perspective on Molecular Insights and Therapeutic Advances
by Shruti Somai, Chioma H. Aloh, Dillon E. King and William C. Copeland
Int. J. Mol. Sci. 2025, 26(21), 10275; https://doi.org/10.3390/ijms262110275 - 22 Oct 2025
Cited by 1 | Viewed by 3552
Abstract
Mitochondria are vital for cellular energy production, as these organelles generate most of the cellular energy required for various metabolic processes. Mitochondria contain their own circular DNA, which is present in multiple copies and is exclusively maternally inherited. Cellular energy in the form [...] Read more.
Mitochondria are vital for cellular energy production, as these organelles generate most of the cellular energy required for various metabolic processes. Mitochondria contain their own circular DNA, which is present in multiple copies and is exclusively maternally inherited. Cellular energy in the form of adenosine 5′-triphosphate is produced via oxidative phosphorylation and involves the coordinated expression of genes encoded by both the nuclear and mitochondrial genomes. Mitochondrial DNA itself is replicated by a dedicated set of nuclear-encoded proteins composed of the DNA polymerase gamma, the Twinkle helicase, the mitochondrial single-stranded DNA binding protein, as well as several accessory factors. Mutations in these genes, as well as in the genes involved in nucleotide metabolism, are associated with a spectrum of mitochondrial disorders that can affect individuals from infancy to old age. Additionally, mitochondrial disease can arise as a result of point mutations, deletions, or depletion in the mitochondrial DNA or in genes involved in mitochondrial transcription, replication, maintenance, and repair. Although a cure for mitochondrial diseases is currently elusive, several treatment options have been explored. In this review, we explore the molecular insights of the core mitochondrial replisome proteins that have aided our understanding of mitochondrial diseases and influenced current therapies. Full article
(This article belongs to the Special Issue Eukaryotic DNA Replication—from Bench to Bedside)
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14 pages, 3484 KB  
Article
The First Heterozygous TWNK Nonsense Mutation Associated with Progressive External Ophthalmoplegia: Evidence for a New Piece in the Puzzle of Mitochondrial Diseases
by Diego Lopergolo, Gianna Berti, Gian Nicola Gallus, Silvia Bianchi, Filippo Maria Santorelli, Alessandro Malandrini and Nicola De Stefano
Biomolecules 2025, 15(9), 1337; https://doi.org/10.3390/biom15091337 - 18 Sep 2025
Viewed by 1677
Abstract
Background: The TWNK gene encodes a protein that colocalizes with mitochondrial DNA (mtDNA) in mitochondrial nucleoids. It acts as mtDNA helicase during replication, thus playing a pivotal role in the replication and maintenance of mtDNA stability. TWNK mutations are associated with a wide [...] Read more.
Background: The TWNK gene encodes a protein that colocalizes with mitochondrial DNA (mtDNA) in mitochondrial nucleoids. It acts as mtDNA helicase during replication, thus playing a pivotal role in the replication and maintenance of mtDNA stability. TWNK mutations are associated with a wide spectrum of clinical phenotypes and a marked heterogeneity. However, heterozygous nonsense variants in the gene have never been described in association with disease. Methods: We analyzed a next-generation sequencing (NGS) targeted gene panel in a cohort including 40 patients with high clinical suspicion of mitochondrial disorders. Selected patients underwent a complete neurological examination, electrophysiology tests, and muscle biopsy. Segregation analysis was performed in available family members. The 3D structure of twinkle was visualized and analyzed using Swiss Model and Pymol version 3.1.6.1. Results: We found four TWNK-mutated subjects from two unrelated families. They exhibited a variable clinical spectrum, ranging from asymptomatic individuals to subjects with psychiatric disorder, chronic progressive external ophthalmoplegia (CPEO), and CPEO-plus. All the subjects shared the heterozygous TWNK p.Glu665Ter variant. Discussion and Conclusions: We describe the clinical phenotype and muscle biopsy findings associated with the first reported heterozygous nonsense TWNK variant, thus expanding the current knowledge of Twinkle-related disorders. Our findings are in line with the high intrafamilial clinical variability associated with TWNK mutations. Although PEO and skeletal muscle involvement remain hallmarks of the disease, extra-muscular features should be carefully assessed. Full article
(This article belongs to the Special Issue Molecular Diagnosis and Regulation of Mitochondrial Dysfunction)
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7 pages, 1733 KB  
Case Report
Bilateral Symmetrical Brain MRI Findings in Acute Necrotising Encephalopathy Type 1
by Alexander T. Hoppe, Twinkle Ghia, Richard Warne, Peter Shipman and Rahul Lakshmanan
Children 2025, 12(8), 974; https://doi.org/10.3390/children12080974 - 24 Jul 2025
Cited by 1 | Viewed by 2825
Abstract
Background: Acute necrotising encephalopathy (ANE) is a rare and severe type of encephalopathy with bilateral symmetrical brain lesions, often following a viral prodrome. ANE type 1 (ANE1) is a disease subtype with a predisposing mutation in the gene encoding RAN binding protein 2 [...] Read more.
Background: Acute necrotising encephalopathy (ANE) is a rare and severe type of encephalopathy with bilateral symmetrical brain lesions, often following a viral prodrome. ANE type 1 (ANE1) is a disease subtype with a predisposing mutation in the gene encoding RAN binding protein 2 (RANBP2). Methods: We report a case of a 3-year-old girl with clinical symptoms of ANE and brain MRI findings suggesting ANE1, which was subsequently confirmed by genetic analysis. Results: MRI of the brain demonstrated symmetrical high T2/FLAIR signal changes in the lateral geniculate bodies, claustrum, ventromedial thalami, subthalamic nuclei, mamillary bodies, and brainstem, with partly corresponding diffusion restriction, as well as additional haemorrhagic changes in the lateral geniculate bodies on susceptibility weighted imaging. Genetic analysis revealed a heterozygous pathogenic variant of the RANBP2 gene. With immunosuppressive and supportive treatment, the patient fully recovered and was discharged after 10 days in the hospital with no residual symptoms. Conclusions: Recognition of the characteristic MRI findings in ANE1 can facilitate a timely diagnosis and enhance the clinical management of the patient and their relatives, especially given the high risk of disease recurrence. Full article
(This article belongs to the Special Issue Genetic Rare Diseases in Children)
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21 pages, 3964 KB  
Article
Emission and Transcriptional Regulation of Aroma Variation in Oncidium Twinkle ‘Red Fantasy’ Under Diel Rhythm
by Yan Chen, Shengyuan Zhong, Lan Kong, Ronghui Fan, Yan Xu, Yiquan Chen and Huaiqin Zhong
Plants 2024, 13(22), 3232; https://doi.org/10.3390/plants13223232 - 17 Nov 2024
Cited by 5 | Viewed by 1956
Abstract
Oncidium hybridum is one of the important cut-flowers in the world. However, the lack of aroma in its cut-flower varieties greatly limits the sustainable development of the Oncidium hybridum cut-flowers industry. This paper is an integral investigation of the diel pattern and influencing [...] Read more.
Oncidium hybridum is one of the important cut-flowers in the world. However, the lack of aroma in its cut-flower varieties greatly limits the sustainable development of the Oncidium hybridum cut-flowers industry. This paper is an integral investigation of the diel pattern and influencing factors of the aroma release of Oncidium Twinkle ‘Red Fantasy’. GC-MS analysis revealed that the release of 3-Carene peaked at 10:00, while Butyl tiglate and Prenyl senecioate did so at 14:00, with a diel rhythm. By analyzing the correlation network between aroma component synthesis and differentially expressed genes, 15 key structural genes were detected and regulated by multiple circadian rhythm-related transcription factors. Cluster-17371.18_TPS, Cluster-65495.1_TPS, Cluster-46699.0_TPS, Cluster-60935.10_DXS, Cluster-47205.4_IDI, and Cluster-65313.7_LOX were key genes in the terpenoid and fatty acid derivative biosynthetic pathway, which were co-expressed with aroma release. Constant light/dark treatments revealed that the diurnal release of 3-Carene may be influenced by light and the circadian clock, and Butyl tiglate and Prenyl senecioate may be mainly determined by endogenous circadian clock. Under constant light treatment, the TPS, DXS, IDI, and LOX genes seem to lose their regulatory role in the release of aroma compounds from Oncidium Twinkle ‘Red Fantasy’. Under constant dark treatment, the TPS genes were consistent with the release pattern of 3-Carene, which may be a key factor in regulating the diel rhythm of 3-Carene biosynthesis. These results laid a theoretical foundation for the study of floral transcriptional regulation and genetic engineering technology breeding of Oncidium hybridum. Full article
(This article belongs to the Special Issue Recent Advances in Horticultural Plant Genomics)
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16 pages, 322 KB  
Article
Reality Does Not Shine, It Twinkles
by William Sulis
Quantum Rep. 2023, 5(4), 609-624; https://doi.org/10.3390/quantum5040040 - 25 Sep 2023
Cited by 3 | Viewed by 2214
Abstract
Arguments have been made that the violation of the CHSH and similar inequalities shows that reality at the quantum level must be non-local. The derivation of Bell inequality is re-examined, and it is shown that violations of these inequalities merely demonstrate the existence [...] Read more.
Arguments have been made that the violation of the CHSH and similar inequalities shows that reality at the quantum level must be non-local. The derivation of Bell inequality is re-examined, and it is shown that violations of these inequalities merely demonstrate the existence of contextuality—they say nothing about the causal influences underlying such contextuality. It is argued that contextual systems do not possess enduring (propositional) properties, merely contingent properties. An example of a classical situation is presented: a two-player co-operative game, the random variables of which are consistently connected in the sense of Dzhafarov, which is contextual, and violates the CHSH inequality. In fact, it also violates the Tsirel’son bound. The key is that this system is generated, and its properties are disposed of, not determined. Full article
22 pages, 2402 KB  
Review
A Comprehensive Review on Bioactive Compounds Found in Caesalpinia sappan
by Twinkle Vij, Pawase Prashant Anil, Rafeeya Shams, Kshirod Kumar Dash, Rhythm Kalsi, Vinay Kumar Pandey, Endre Harsányi, Béla Kovács and Ayaz Mukarram Shaikh
Molecules 2023, 28(17), 6247; https://doi.org/10.3390/molecules28176247 - 25 Aug 2023
Cited by 78 | Viewed by 14834
Abstract
Sappan wood (Caesalpinia sappan) is a tropical hardwood tree found in Southeast Asia. Sappan wood contains a water-soluble compound, which imparts a red color named brazilin. Sappan wood is utilized to produce dye for fabric and coloring agents for food and [...] Read more.
Sappan wood (Caesalpinia sappan) is a tropical hardwood tree found in Southeast Asia. Sappan wood contains a water-soluble compound, which imparts a red color named brazilin. Sappan wood is utilized to produce dye for fabric and coloring agents for food and beverages, such as wine and meat. As a valuable medicinal plant, the tree is also known for its antioxidant, anti-inflammatory, and anticancer properties. It has been observed that sappan wood contains various bioactive compounds, including brazilin, brazilein, sappan chalcone, and protosappanin A. It has also been discovered that these substances have various health advantages; they lower inflammation, enhance blood circulation, and are anti-oxidative in nature. Sappan wood has been used as a medicine to address a range of illnesses, such as gastrointestinal problems, respiratory infections, and skin conditions. Studies have also suggested that sappan wood may have anticarcinogenic potential as it possesses cytotoxic activity against cancer cells. Based on this, the present review emphasized the different medicinal properties, the role of phytochemicals, their health benefits, and several food and nonfood applications of sappan wood. Overall, sappan wood has demonstrated promising medicinal properties and is an important resource in traditional medicine. The present review has explored the potential role of sappan wood as an essential source of bioactive compounds for drug development. Full article
(This article belongs to the Special Issue Natural Bioactive Compounds and Human Health)
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18 pages, 1537 KB  
Review
Microbe-Plant Interactions Targeting Metal Stress: New Dimensions for Bioremediation Applications
by Baljeet Singh Saharan, Twinkle Chaudhary, Balwan Singh Mandal, Dharmender Kumar, Ravinder Kumar, Pardeep Kumar Sadh and Joginder Singh Duhan
J. Xenobiotics 2023, 13(2), 252-269; https://doi.org/10.3390/jox13020019 - 1 Jun 2023
Cited by 29 | Viewed by 5792
Abstract
In the age of industrialization, numerous non-biodegradable pollutants like plastics, HMs, polychlorinated biphenyls, and various agrochemicals are a serious concern. These harmful toxic compounds pose a serious threat to food security because they enter the food chain through agricultural land and water. Physical [...] Read more.
In the age of industrialization, numerous non-biodegradable pollutants like plastics, HMs, polychlorinated biphenyls, and various agrochemicals are a serious concern. These harmful toxic compounds pose a serious threat to food security because they enter the food chain through agricultural land and water. Physical and chemical techniques are used to remove HMs from contaminated soil. Microbial-metal interaction, a novel but underutilized strategy, might be used to lessen the stress caused by metals on plants. For reclaiming areas with high levels of heavy metal contamination, bioremediation is effective and environmentally friendly. In this study, the mechanism of action of endophytic bacteria that promote plant growth and survival in polluted soils—known as heavy metal-tolerant plant growth-promoting (HMT-PGP) microorganisms—and their function in the control of plant metal stress are examined. Numerous bacterial species, such as Arthrobacter, Bacillus, Burkholderia, Pseudomonas, and Stenotrophomonas, as well as a few fungi, such as Mucor, Talaromyces, Trichoderma, and Archaea, such as Natrialba and Haloferax, have also been identified as potent bioresources for biological clean-up. In this study, we additionally emphasize the role of plant growth-promoting bacteria (PGPB) in supporting the economical and environmentally friendly bioremediation of heavy hazardous metals. This study also emphasizes future potential and constraints, integrated metabolomics approaches, and the use of nanoparticles in microbial bioremediation for HMs. Full article
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14 pages, 7742 KB  
Review
Structural and Molecular Basis for Mitochondrial DNA Replication and Transcription in Health and Antiviral Drug Toxicity
by Joon Park, Noe Baruch-Torres and Y. Whitney Yin
Molecules 2023, 28(4), 1796; https://doi.org/10.3390/molecules28041796 - 14 Feb 2023
Cited by 15 | Viewed by 8110
Abstract
Human mitochondrial DNA (mtDNA) is a 16.9 kbp double-stranded, circular DNA, encoding subunits of the oxidative phosphorylation electron transfer chain and essential RNAs for mitochondrial protein translation. The minimal human mtDNA replisome is composed of the DNA helicase Twinkle, DNA polymerase γ, and [...] Read more.
Human mitochondrial DNA (mtDNA) is a 16.9 kbp double-stranded, circular DNA, encoding subunits of the oxidative phosphorylation electron transfer chain and essential RNAs for mitochondrial protein translation. The minimal human mtDNA replisome is composed of the DNA helicase Twinkle, DNA polymerase γ, and mitochondrial single-stranded DNA-binding protein. While the mitochondrial RNA transcription is carried out by mitochondrial RNA polymerase, mitochondrial transcription factors TFAM and TFB2M, and a transcription elongation factor, TEFM, both RNA transcriptions, and DNA replication machineries are intertwined and control mtDNA copy numbers, cellular energy supplies, and cellular metabolism. In this review, we discuss the mechanisms governing these main pathways and the mtDNA diseases that arise from mutations in transcription and replication machineries from a structural point of view. We also address the adverse effect of antiviral drugs mediated by mitochondrial DNA and RNA polymerases as well as possible structural approaches to develop nucleoside reverse transcriptase inhibitor and ribonucleosides analogs with reduced toxicity. Full article
(This article belongs to the Special Issue Small Molecule Inhibitors of Polymerases Involved in Human Diseases)
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14 pages, 1100 KB  
Systematic Review
Echogenic Content in the Fetal Gallbladder: Systematic Review of Ultrasound Features and Clinical Outcome
by Dan Boitor-Borza, Ioana Cristina Rotar, Adelina Staicu, Roxana Constantin and Daniel Muresan
Diagnostics 2023, 13(2), 230; https://doi.org/10.3390/diagnostics13020230 - 8 Jan 2023
Cited by 3 | Viewed by 8679
Abstract
It is rare to detect echogenic content in the fetal gallbladder. The etiology, natural course, and prognosis of this condition remain unclear. In addition to providing a systematic review of this topic, we suggest a plan for patient follow-up. From a total of [...] Read more.
It is rare to detect echogenic content in the fetal gallbladder. The etiology, natural course, and prognosis of this condition remain unclear. In addition to providing a systematic review of this topic, we suggest a plan for patient follow-up. From a total of 100 database entries identified in PubMed, EMBASE, and ICTRP reviews, we selected 34 studies in which we investigated the ultrasound features and outcome of this condition. There were 226 fetuses with gallbladder echogenic content identified. Seventy-two fetuses were found to have biliary sludge; thirty cases had a single hyperechogenic focus, and one hundred fetuses had multiple foci in the gallbladder. There were 16 cases of distal shadowing, 37 fetuses with comet tail and twinkling, and 26 cases with no acoustic artifacts. Nine cases of spontaneous resolution before birth have been documented; nine fetuses exhibited no echogenic content at birth, and 138 cases of resolution of echogenic content within the first year of life have been described. Typically, the condition resolves spontaneously during the postnatal period. After adequately reassuring the parents, the patients should be monitored for spontaneous resolution; medical or surgical intervention is not indicated. Asymptomatic patients can be managed with a wait-and-see strategy. Full article
(This article belongs to the Special Issue Prenatal Diagnosis: Current Trends and Future Directions)
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33 pages, 3508 KB  
Article
CLPP Depletion Causes Diplotene Arrest; Underlying Testis Mitochondrial Dysfunction Occurs with Accumulation of Perrault Proteins ERAL1, PEO1, and HARS2
by Jana Key, Suzana Gispert, Lieke Koornneef, Esther Sleddens-Linkels, Aneesha Kohli, Sylvia Torres-Odio, Gabriele Koepf, Shady Amr, Marina Reichlmeir, Patrick N. Harter, Andrew Phillip West, Christian Münch, Willy M. Baarends and Georg Auburger
Cells 2023, 12(1), 52; https://doi.org/10.3390/cells12010052 - 22 Dec 2022
Cited by 13 | Viewed by 5050
Abstract
Human Perrault syndrome (PRLTS) is autosomal, recessively inherited, and characterized by ovarian insufficiency with hearing loss. Among the genetic causes are mutations of matrix peptidase CLPP, which trigger additional azoospermia. Here, we analyzed the impact of CLPP deficiency on male mouse meiosis stages. [...] Read more.
Human Perrault syndrome (PRLTS) is autosomal, recessively inherited, and characterized by ovarian insufficiency with hearing loss. Among the genetic causes are mutations of matrix peptidase CLPP, which trigger additional azoospermia. Here, we analyzed the impact of CLPP deficiency on male mouse meiosis stages. Histology, immunocytology, different OMICS and biochemical approaches, and RT-qPCR were employed in CLPP-null mouse testis. Meiotic chromosome pairing and synapsis proceeded normally. However, the foci number of the crossover marker MLH1 was slightly reduced, and foci persisted in diplotene, most likely due to premature desynapsis, associated with an accumulation of the DNA damage marker γH2AX. No meiotic M-phase cells were detected. Proteome profiles identified strong deficits of proteins involved in male meiotic prophase (HSPA2, SHCBP1L, DMRT7, and HSF5), versus an accumulation of AURKAIP1. Histone H3 cleavage, mtDNA extrusion, and cGAMP increase suggested innate immunity activation. However, the deletion of downstream STING/IFNAR failed to alleviate pathology. As markers of underlying mitochondrial pathology, we observed an accumulation of PRLTS proteins ERAL1, PEO1, and HARS2. We propose that the loss of CLPP leads to the extrusion of mitochondrial nucleotide-binding proteins to cytosol and nucleus, affecting late meiotic prophase progression, and causing cell death prior to M-phase entry. This phenotype is more severe than in mito-mice or mutator-mice. Full article
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