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Abstract Background Microplastics are ubiquitous, widespread environmental pollutants with unavoidable human exposure. Herein, it was aimed to investigate the presence of microplastics in prostate tissue. Methods Prostate tissues from 12 patients who underwent Trans Urethral Resection of the Prostate (TUR-P) were analyzed to investigate the presence of microplastics. Initially, the prostate tissues were analyzed for microplastic particles using a light microscope after extraction. Subsequently, the chemical composition of the particles found in the prostate tissues was characterized using Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) spectrophotometry. Results Microplastic particles of various types were detected in 6 out of 12 patients. All detected plastic particles in this study were microplastics, with sizes below 26 μm in size. These microplastics exhibited different shapes as pellets, spheres or fibers. Overall, among the 12 analyzed prostate tissue samples, four different types of plastic were identified in six samples. The most common type of microplastic detected was Polyamide (Nylon 6), found in samples from three patients. Other detected types, Polypropylene, Polyacrylic Acid and Poly (dimethylsiloxane) were each determined in samples from one patient. Conclusions This is the first study to demonstrate the presence of microplastics in prostate tissue, serving as an exploratory investigation, which can trigger further research to validate the results in a larger patient cohort.

PURPOSEWe aimed to investigate the accuracy of Vesical Imaging - Reporting and Data System (VI-RADS) in the detection of muscle-invasive bladder cancer (MIBC) and to determine which factors affect the results of this scoring system.METHODSA prospective data analysis of 80 patients who were detected to have bladder tumor was performed between March 2019 and October 2020. VI-RADS scoring was used to determine the probability of muscle invasion. The scores were compared with pathological results to evaluate the accuracy of the VI-RADS scoring system. Interobserver agreement was assessed by VI-RADS scoring of 20 randomly chosen patients by a different experienced radiologist.RESULTSUsing the VI-RADS scoring system, the sensitivity, specificity, positive predictive value, and negative predictive value of multiparametric magnetic resonance imaging (mpMRI) were 87.5%, 87.5%, 63.6%, and 96.6%, respectively. The interobserver agreement expressed as the interclass correlation coefficient (ICC) was 0.72 (95% CI: 0.44-0.84, P < .001). In addition, the flat appearance of the tumor was an important factor affecting the accuracy of the VI-RADS score (odds ratio: 5.3 [95% CI: 1.1-27.0] and relative risk: 1.87 [95% CI: 1.24-2.82]).CONCLUSIONThe mpMRI, used in conjunction with VI-RADS, has proven to be an effective imaging method for detecting muscle invasion in cases of bladder cancer. VI-RADS scoring system can distinguish whether there is a muscle-invasive and non-muscle invasive bladder cancer with acceptable accuracy. In addition, the flat appearance of the tumor is an important entity that can affect the accuracy of the VI-RADS scoring system.

Bu çalışmanın amacı, Türkiye’nin başta Azerbaycan olmak üzere, Gürcistan ile kurduğu ekonomik ve siyasi ilişkilerine askeri boyutu da dâhil etmesinin bölgesel güvenliğe olumlu yönde katkı sağlayacağını ortaya koymaktır. Türkiye, ekonomik ve siyasi alanlarda başlattığı ilişkileri her üç ülkenin de çıkarına uygun olacak şekilde güvenlik alanına taşımak istemekte; böylece Güney Kafkasya’yı bir “güvenlik bölgesi” haline getirmeye çalışmaktadır. Bu sayede bölgede Rusya Federasyonu ve Ermenistan’a karşı da bir denge sağlanmakla birlikte, kendisine doğudan gelecek tehditlere karşı bir ittifak kurulmuş olacaktır. Ayrıca, Türkiye NATO üyeliği kapsamında edindiği bilgi ve tecrübeyi gerek Azerbaycan’a gerekse Gürcistan’a aktararak bu ülkelerin NATO üyeliğine hazırlanmalarına da katkı sağlayacaktır.

Sixty-four lentil genotypes from ICARDA were evaluated at Diyarbakir, Turkey in 2003/2004 season. Eleven characters were studied. Days to maturity ranged from 188 to 196 days, and some genotypes were earlier than the local check, or same. Total 42 genotypes, suitable for mechanical harvest, were taller than 25 cm plant height. Seed yield per plant varied from 0.5 g to 2.366 g. The genotypes for cold tolerance were determined, and the genotypes of 1-3 scale were selected future lentil-breeding programme. Grain yield ranged from 776.8 kg/ha for FLIP 96-47L to 3242.3 kg/ha for FLIP 2004-49L. Grain yield was positively correlated with days to maturity, biological yield per plant, and plant height, number of seeds and pods per plant and seed yield per plant, negatively correlated with days to flowering and number of branches per plant.

Twenty-nine lentil (Lens culinaris Medik) genotypes were grown from 1997/98 to 1998/2001 at Dicle University, Faculty of Agriculture in Diyarbakir The heritability for days to fl owering and maturity, plant height, height of lowest pod, number of pod per plant, 1000 seed weight and seed yield were estimated as 0.94, 0.78, 0.52, 0.72, 0.37, 0.87 and 0.53, respectively. The path analysis indicated that total biological yield and number of clusters and pods per plant had very high positive direct effect on seed yield.

Chickpea (Cicer arietinum L.) is the third most important pulse crop (after dry bean and pea) and makes up 20% of the world pulse production. Twelve chickpea crosses, from ILC482 and Diyar 95 crossing, and four chickpea varieties were evaluated for yield and its components over three years in Diyarbakir, Turkey. Days to flowering in crosses was changed from 75.42 to 79.92 days. Days to maturity were varied from 109.0 to 120.2 days. Parents had the minimum and maximum time to flowering and maturity. Some crosses were taller than their parents were. Seed weight of all crosses was larger than the small seeded parent ILC 482. Grain yield was not changed among lines, and selection was done for earliness, plant height and seed weight.

Fourteen lentil genotypes were tested for grain yield in Southeastern Anatolia ecological conditions, over our consecutive years to classify these cultivars for yield stability. Seed yield ranged from 1.903 t/ha to 1.367 t/ha. RM76, RM601 and RM152 showed regression coeffi cient above 1.00, but RM76 among these lines was consistently produced the highest yields. The unstable cultivars, RM601 and RM152 had the highest S2 values and high C.V. for grain yield.

Transcoding is an effective method to provide video adaptation for heterogeneous internetwork video access and communication environments, which require the tailoring (i.e., repurposing) of coded video properties to channel conditions, terminal capabilities, and user preferences. This paper presents a video transcoding system that is capable of applying a suite of error resilience tools on the input compressed video streams while controlling the output rates to provide robust communications over error-prone and bandwidth-limited 3G wireless networks. The transcoder is also designed to employ a new adaptive intra-refresh algorithm, which is responsive to the detected scene activity inherently embedded into the video content and the reported time-varying channel error conditions of the wireless network. Comprehensive computer simulations demonstrate significant improvements in the received video quality performances using the new transcoding architecture without an extra computational cost.

Cystathionine beta-synthase deficiency (CBSD) is the most prevalent inherited disorder of homocysteine metabolism in the transsulphuration pathway. Research have suggested oxidative stress and inflammation as candidate pathogenic mechanisms in CBSD. This study aims to evaluate mitochondrial dysfunction and oxidative stress biomarkers in cystathionine beta-synthase deficiency (CBSD) patients, which may aid in understanding the pathogenesis of CBSD and improving treatment. The study group comprised 23 patients with a diagnosis of CBSD and healthy controls. We analysed serum levels of NAD + and NADH by fluorometric assay, FGF-21 and GDF-15 by ELISA, mitochondrial DAMPs by real time qRT-PCR, total homocysteine levels in plasma by enzymatic test and compared the results in CBSD group with healthy controls. In patient group, a positive correlation was found between the total homocysteine level and both GDF-15 and NAD + /NADH levels. Furthermore, there was a negative correlation between total homocysteine levels and both total NAD + +NADH and NADH levels. The alterations in NAD + , FGF-21, GDF-15 levels, and NAD + /NADH ratio in patients suggest that oxidative damage coexists with mitochondrial dysfunction in CBSD. Assessment of oxidative damage and addition of anti-oxidant therapy together with mitochondrial support may have additional benefits in reducing long-term morbidity in CBSD patients., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: An ethical approval (file number; 2023/1637) was obtained from Istanbul Faculty of Medicine Ethics Committee before the study and written informed consent was obtained from each patient or guardian., (© 2024. The Author(s).)

Background: Tumour-induced skeletal muscle wasting in the context of cancer cachexia is a condition with profound implications for patient survival. The loss of muscle mass is a significant clinical obstacle and is linked to reduced tolerance to chemotherapy and increased frailty. Understanding the molecular mechanisms driving muscle atrophy is crucial for the design of new therapeutics., Methods: Lewis lung carcinoma tumours were utilized to induce cachexia and muscle atrophy in mice. Single-nucleus libraries of the tibialis anterior (TA) muscle from tumour-bearing mice and their non-tumour-bearing controls were constructed using 10X Genomics applications following the manufacturer's guidelines. RNA sequencing results were analysed with Cell Ranger software and the Seurat R package. Oxygen consumption of mitochondria isolated from TA muscle was measured using an Oroboros O2k-FluoRespirometer. Mouse primary myotubes were treated with a recombinant ectodysplasin A2 (EDA-A2) protein to activate EDA-A2 receptor (EDA2R) signalling and study changes in gene expression and oxygen consumption., Results: Tumour-bearing mice were sacrificed while exhibiting moderate cachexia. Average TA muscle weight was reduced by 11% (P = 0.0207) in these mice. A total of 12 335 nuclei, comprising 6422 nuclei from the control group and 5892 nuclei from atrophying muscles, were studied. The analysis of single-nucleus transcriptomes identified distinct myonuclear gene signatures and a shift towards type IIb myonuclei. Muscle atrophy-related genes, including Atrogin1, MuRF1 and Eda2r, were upregulated in these myonuclei, emphasizing their crucial roles in muscle wasting. Gene set enrichment analysis demonstrated that EDA2R activation and tumour inoculation led to similar expression patterns in muscle cells, including the stimulation of nuclear factor-kappa B, Janus kinase-signal transducer and activator of transcription and transforming growth factor-beta pathways and the suppression of myogenesis and oxidative phosphorylation. Muscle oxidative metabolism was suppressed by both tumours and EDA2R activation., Conclusions: This study identified tumour-induced transcriptional changes in muscle tissue at single-nucleus resolution and highlighted the negative impact of tumours on oxidative metabolism. These findings contribute to a deeper understanding of the molecular mechanisms underlying muscle wasting., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Significance: Reactive oxygen species (ROS) are highly reactive compounds that behave like a double-edged sword; they damage cellular structures and act as second messengers in signal transduction. Mitochondria and endoplasmic reticulum (ER) are interconnected organelles with a central role in ROS production, detoxification, and oxidative stress response. Skeletal muscle is the most abundant tissue in mammals and one of the most metabolically active ones and thus relies mainly on oxidative phosphorylation (OxPhos) to synthesize adenosine triphosphate. The impairment of OxPhos leads to myopathy and increased ROS production, thus affecting both redox poise and signaling. In addition, ROS enter the ER and trigger ER stress and its maladaptive response, which also lead to a myopathic phenotype with mitochondrial involvement. Here, we review the role of ROS signaling in myopathies due to either mitochondrial or ER dysfunction. Recent Advances: Relevant advances have been evolving over the last 10 years on the intricate ROS-dependent pathways that act as modifiers of the disease course in several myopathies. To this end, pathways related to mitochondrial biogenesis, satellite cell differentiation, and ER stress have been studied extensively in myopathies. Critical Issues: The analysis of the chemistry and the exact quantitation, as well as the localization of ROS, are still challenging due to the intrinsic labile nature of ROS and the technical limitations of their sensors. Future Directions: The mechanistic studies of the pathogenesis of mitochondrial and ER-related myopathies offer a unique possibility to discover novel ROS-dependent pathways. Antioxid. Redox Signal . 37, 301-323.

Mutations in POLG, encoding POLγA, the catalytic subunit of the mitochondrial DNA polymerase, cause a spectrum of disorders characterized by mtDNA instability. However, the molecular pathogenesis of POLG-related diseases is poorly understood and efficient treatments are missing. Here, we generate the PolgA449T/A449T mouse model, which reproduces the A467T change, the most common human recessive mutation of POLG. We show that the mouse A449T mutation impairs DNA binding and mtDNA synthesis activities of POLγ, leading to a stalling phenotype. Most importantly, the A449T mutation also strongly impairs interactions with POLγB, the accessory subunit of the POLγ holoenzyme. This allows the free POLγA to become a substrate for LONP1 protease degradation, leading to dramatically reduced levels of POLγA in A449T mouse tissues. Therefore, in addition to its role as a processivity factor, POLγB acts to stabilize POLγA and to prevent LONP1-dependent degradation. Notably, we validated this mechanism for other disease-associated mutations affecting the interaction between the two POLγ subunits. We suggest that targeting POLγA turnover can be exploited as a target for the development of future therapies., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Alternative oxidases (AOXs) bypass respiratory complexes III and IV by transferring electrons from coenzyme Q directly to O 2 . They have therefore been proposed as a potential therapeutic tool for mitochondrial diseases. We crossed the severely myopathic skeletal muscle-specific COX15 knockout (KO) mouse with an AOX-transgenic mouse. Surprisingly, the double KO-AOX mutants had decreased lifespan and a substantial worsening of the myopathy compared with KO alone. Decreased ROS production in KO-AOX versus KO mice led to impaired AMPK/PGC-1α signaling and PAX7/MYOD-dependent muscle regeneration, blunting compensatory responses. Importantly, the antioxidant N-acetylcysteine had a similar effect, decreasing the lifespan of KO mice. Our findings have major implications for understanding pathogenic mechanisms in mitochondrial diseases and for the design of therapies, highlighting the benefits of ROS signaling and the potential hazards of antioxidant treatment., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

The mTOR inhibitor rapamycin ameliorates the clinical and biochemical phenotype of mouse, worm, and cellular models of mitochondrial disease, via an unclear mechanism. Here, we show that prolonged rapamycin treatment improved motor endurance, corrected morphological abnormalities of muscle, and increased cytochrome c oxidase (COX) activity of a muscle-specific Cox15 knockout mouse ( Cox15 sm / sm ). Rapamycin treatment restored autophagic flux, which was impaired in naïve Cox15 sm / sm muscle, and reduced the number of damaged mitochondria, which accumulated in untreated Cox15 sm / sm mice. Conversely, rilmenidine, an mTORC1-independent autophagy inducer, was ineffective on the myopathic features of Cox15 sm / sm animals. This stark difference supports the idea that inhibition of mTORC1 by rapamycin has a key role in the improvement of the mitochondrial function in Cox15 sm / sm muscle. In contrast to rilmenidine, rapamycin treatment also activated lysosomal biogenesis in muscle. This effect was associated with increased nuclear localization of TFEB, a master regulator of lysosomal biogenesis, which is inhibited by mTORC1-dependent phosphorylation. We propose that the coordinated activation of autophagic flux and lysosomal biogenesis contribute to the effective clearance of dysfunctional mitochondria by rapamycin., (© 2018 The Authors. Published under the terms of the CC BY 4.0 license.)

Although mitochondria are ubiquitous, each mitochondrial disease has surprisingly distinctly different pattern of tissue and organ involvement. Congruently, mutations in genes encoding for different mitochondrial tRNA synthetases result in the development of a very flamboyant group of diseases. Mutations in some of these genes, including aspartyl-tRNA synthetase (DARS2), lead to the onset of a white matter disease-leukoencephalopathy with brainstem and spinal cord involvement, and lactate elevation (LBSL) characterized by progressive spastic ataxia and characteristic leukoencephalopathy signature with multiple long-tract involvements. Puzzled by the white matter disease phenotypes caused by DARS2 deficiency when numerous other mutations in the genes encoding proteins involved in mitochondrial translation have a detrimental effect predominantly on neurons, we generated transgenic mice in which DARS2 was specifically depleted in forebrain-hippocampal neurons or myelin-producing cells. Our results now provide the first evidence that loss of DARS2 in adult neurons leads to strong mitochondrial dysfunction and progressive loss of cells. In contrast, myelin-producing cells seem to be resistant to cell death induced by DARS2 depletion despite robust respiratory chain deficiency arguing that LBSL might originate from the primary neuronal and axonal defect. Remarkably, our results also suggest a role for early neuroinflammation in the disease progression, highlighting the possibility for therapeutic interventions of this process., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Loss-of-function mutations in TTC19 (tetra-tricopeptide repeat domain 19) have been associated with severe neurological phenotypes and mitochondrial respiratory chain complex III deficiency. We previously demonstrated the mitochondrial localization of TTC19 and its link with complex III biogenesis. Here we provide detailed insight into the mechanistic role of TTC19, by investigating a Ttc19 ?/? mouse model that shows progressive neurological and metabolic decline, decreased complex III activity, and increased production of reactive oxygen species. By using both the Ttc19 ?/? mouse model and a range of human cell lines, we demonstrate that TTC19 binds to the fully assembled complex III dimer, i.e., after the incorporation of the iron-sulfur Rieske protein (UQCRFS1). The in situ maturation of UQCRFS1 produces N-terminal polypeptides, which remain bound to holocomplex III. We show that, in normal conditions, these UQCRFS1 fragments are rapidly removed, but when TTC19 is absent they accumulate within complex III, causing its structural and functional impairment., (Copyright © 2017. Published by Elsevier Inc.)

Although mitochondrial dysfunction is often accompanied by excessive reactive oxygen species (ROS) production, we previously showed that an increase in random somatic mtDNA mutations does not result in increased oxidative stress. Normal levels of ROS and oxidative stress could also be a result of an active compensatory mechanism such as a mild increase in proton leak. Uncoupling protein 2 (UCP2) was proposed to play such a role in many physiological situations. However, we show that upregulation of UCP2 in mtDNA mutator mice is not associated with altered proton leak kinetics or ROS production, challenging the current view on the role of UCP2 in energy metabolism. Instead, our results argue that high UCP2 levels allow better utilization of fatty acid oxidation resulting in a beneficial effect on mitochondrial function in heart, postponing systemic lactic acidosis and resulting in longer lifespan in these mice. This study proposes a novel mechanism for an adaptive response to mitochondrial cardiomyopathy that links changes in metabolism to amelioration of respiratory chain deficiency and longer lifespan.

Adaptive stress responses activated upon mitochondrial dysfunction are assumed to arise in order to counteract respiratory chain deficiency. Here, we demonstrate that loss of DARS2 (mitochondrial aspartyl-tRNA synthetase) leads to the activation of various stress responses in a tissue-specific manner independently of respiratory chain deficiency. DARS2 depletion in heart and skeletal muscle leads to the severe deregulation of mitochondrial protein synthesis followed by a strong respiratory chain deficit in both tissues, yet the activation of adaptive responses is observed predominantly in cardiomyocytes. We show that the impairment of mitochondrial proteostasis in the heart activates the expression of mitokine FGF21, which acts as a signal for cell-autonomous and systemic metabolic changes. Conversely, skeletal muscle has an intrinsic mechanism relying on the slow turnover of mitochondrial transcripts and higher proteostatic buffering capacity. Our results show that mitochondrial dysfunction is sensed independently of respiratory chain deficiency, questioning the current view on the role of stress responses in mitochondrial diseases., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Understanding mitochondrial role in normal physiology and pathological conditions has proven to be of high importance as mitochondrial dysfunction is connected with a number of disorders as well as some of the most common diseases (e.g. diabetes or Parkinson's disease). Modeling mitochondrial dysfunction has been difficult mainly due to unique features of mitochondrial genetics. Here we discuss some of the most important mouse models generated so far and lessons learned from them.