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Abstract The number of tRNA isodecoders has increased dramatically in mammals, but the specific molecular and physiological reasons for this expansion remain elusive. To address this fundamental question we used CRISPR editing to knockout the seven-membered phenylalanine tRNA gene family in mice, both individually and combinatorially. Using ATAC-Seq, RNA-seq, ribo-profiling and proteomics we observed distinct molecular consequences of single tRNA deletions. We show that tRNA-Phe-1-1 is required for neuronal function and its loss is partially compensated by increased expression of other tRNAs but results in mistranslation. In contrast, the other tRNA-Phe isodecoder genes buffer the loss of each of the remaining six tRNA-Phe genes. In the tRNA-Phe gene family, the expression of at least six tRNA-Phe alleles is required for embryonic viability and tRNA-Phe-1-1 is most important for development and survival. Our results reveal that the multi-copy configuration of tRNA genes is required to buffer translation and viability in mammals.

Abstract Prostate cancer is the most commonly diagnosed malignancy and the third leading cause of cancer deaths. GWAS have identified variants associated with prostate cancer susceptibility; however, mechanistic and functional validation of these mutations is lacking. We used CRISPR‐Cas9 genome editing to introduce a missense variant identified in the ELAC2 gene, which encodes a dually localised nuclear and mitochondrial RNA processing enzyme, into the mouse Elac2 gene as well as to generate a prostate‐specific knockout of Elac2. These mutations caused enlargement and inflammation of the prostate and nodule formation. The Elac2 variant or knockout mice on the background of the transgenic adenocarcinoma of the mouse prostate (TRAMP) model show that Elac2 mutation with a secondary genetic insult exacerbated the onset and progression of prostate cancer. Multiomic profiling revealed defects in energy metabolism that activated proinflammatory and tumorigenic pathways as a consequence of impaired noncoding RNA processing and reduced protein synthesis. Our physiologically relevant models show that the ELAC2 variant is a predisposing factor for prostate cancer and identify changes that underlie the pathogenesis of this cancer.

Summary: Platelets are anucleate blood cells that contain mitochondria and regulate blood clotting in response to injury. Mitochondria contain their own gene expression machinery that relies on nuclear-encoded factors for the biogenesis of the oxidative phosphorylation system to produce energy required for thrombosis. The autonomy of the mitochondrial gene expression machinery from the nucleus is unclear, and platelets provide a valuable model to understand its importance in anucleate cells. Here, we conditionally delete Elac2, Ptcd1, or Mtif3 in platelets, which are essential for mitochondrial gene expression at the level of RNA processing, stability, or translation, respectively. Loss of ELAC2, PTCD1, or MTIF3 leads to increased megakaryocyte ploidy, elevated circulating levels of reticulated platelets, thrombocytopenia, and consequent extended bleeding time. Impaired mitochondrial gene expression reduces agonist-induced platelet activation. Transcriptomic and proteomic analyses show that mitochondrial gene expression is required for fibrinolysis, hemostasis, and blood coagulation in response to injury.

IntroductionThe CIAO project was launched in Spring 2020 to address the need to make sense of the numerous and disparate data available on COVID-19 pathogenesis. Based on a crowdsourcing model of large-scale collaboration, the project has exploited the Adverse Outcome Pathway (AOP) knowledge management framework built to support chemical risk assessment driven by mechanistic understanding of the biological perturbations at the different organizational levels. Hence the AOPs might have real potential to integrate data produced through different approaches and from different disciplines as experienced in the context of COVID-19. In this study, we aim to address the effectiveness of the AOP framework (i) in supporting an interdisciplinary collaboration for a viral disease and (ii) in working as the conceptual mediator of a crowdsourcing model of collaboration.MethodsWe used a survey disseminated among the CIAO participants, a workshop open to all interested CIAO contributors, a series of interviews with some participants and a self-reflection on the processes.ResultsThe project has supported genuine interdisciplinarity with exchange of knowledge. The framework provided a common reference point for discussion and collaboration. The diagram used in the AOPs assisted with making explicit what are the different perspectives brought to the knowledge about the pathways. The AOP-Wiki showed up many aspects about its usability for those not already in the world of AOPs. Meanwhile their use in CIAO highlighted needed adaptations. Introduction of new Wiki elements for modulating factors was potentially the most disruptive one. Regarding how well AOPs support a crowdsourcing model of large-scale collaboration, the CIAO project showed that this is successful when there is a strong central organizational impetus and when clarity about the terms of the collaboration is brought as early as possible.DiscussionExtrapolate the successful CIAO approach and related processes to other areas of science where the AOP could foster interdisciplinary and systematic organization of the knowledge is an exciting perspective.

A subset of mitochondrial transcripts is not flanked by tRNAs and thus does not conform to the canonical mode of processing. Here, Clemente et al. demonstrate that phosphatase activity of ANGEL2 is required for correct processing of these transcripts.

The ability to alter the genomes of living cells is key to understanding how genes influence the functions of organisms and will be critical to modify living systems for useful purposes. Here, the authors use computational design to discover Cas9 enzymes with increased activity.

There are different approaches used to reduce reading skills deficits. One such approach, which belongs to the group of visual adaptations, is to change the font used in the texts. The main research goal is to assess the level of reading success in people with dyslexia (reading difficulties) by using a specialized Cyrillic font - Dyslexic FZF. The research was conducted on 24 persons with dyslexia from North Macedonia and obtained data about oral reading fluency and reading lists of meaningful and meaningless words with the Dyslexic FZF font and the font Times New Roman. The data of the two consecutive readings were compared. Results suggest that when using the new dyslexia typeface, Dyslexic FZF, participants were able to read more words per minute than with the Times New Roman font. A statistically significant difference in the results occurs in the errors made while reading.

Mammalian mitoribosomes feature dramatically reduced ribosomal RNAs and follow mitochondria specific assembly pathways. Here the authors describe the process of human mitochondrial ribosome maturation that results in the formation of the ribosomal active site region, including the peptidyl transferase loop and the two tRNA-binding loops.

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are formed as a result of natural cellular processes, intracellular signaling, or as adverse responses associated with diseases or exposure to oxidizing chemical and non-chemical stressors. The action of ROS and RNS, collectively referred to as reactive oxygen and nitrogen species (RONS), has recently become highly relevant in a number of adverse outcome pathways (AOPs) that capture, organize, evaluate and portray causal relationships pertinent to adversity or disease progression. RONS can potentially act as a key event (KE) in the cascade of responses leading to an adverse outcome (AO) within such AOPs, but are also known to modulate responses of events along the AOP continuum without being an AOP event itself. A substantial discussion has therefore been undertaken in a series of workshops named “Mystery or ROS” to elucidate the role of RONS in disease and adverse effects associated with exposure to stressors such as nanoparticles, chemical, and ionizing and non-ionizing radiation. This review introduces the background for RONS production, reflects on the direct and indirect effects of RONS, addresses the diversity of terminology used in different fields of research, and provides guidance for developing a harmonized approach for defining a common event terminology within the AOP developer community.

Transcription of the human mitochondrial genome and correct processing of the two long polycistronic transcripts are crucial for oxidative phosphorylation. According to the tRNA punctuation model, nucleolytic processing of these large precursor transcripts occurs mainly through the excision of the tRNAs that flank most rRNAs and mRNAs. However, some mRNAs are not punctuated by tRNAs, and it remains largely unknown how these non-canonical junctions are resolved. The FASTK family proteins are emerging as key players in non-canonical RNA processing. Here, we have generated human cell lines carrying single or combined knockouts of several FASTK family members to investigate their roles in non-canonical RNA processing. The most striking phenotypes were obtained with loss of FASTKD4 and FASTKD5 and with their combined double knockout. Comprehensive mitochondrial transcriptome analyses of these cell lines revealed a defect in processing at several canonical and non-canonical RNA junctions, accompanied by an increase in specific antisense transcripts. Loss of FASTKD5 led to the most severe phenotype with marked defects in mitochondrial translation of key components of the electron transport chain complexes and in oxidative phosphorylation. We reveal that the FASTK protein family members are crucial regulators of non-canonical junction and non-coding mitochondrial RNA processing.

Transcription of the human mitochondrial genome and correct processing of the two long polycistronic transcripts are crucial for oxidative phosphorylation. According to the tRNA punctuation model, nucleolytic processing of these large precursor transcripts occurs mainly through the excision of the tRNAs that flank most rRNAs and mRNAs. However, some mRNAs are not punctuated by tRNAs, and it remains largely unknown how these non-canonical junctions are resolved. The FASTK family proteins are emerging as key players in non-canonical RNA processing. Here, we have generated human cell lines carrying single or combined knockouts of several FASTK family members to investigate their roles in non-canonical RNA processing. The most striking phenotypes were obtained with loss of FASTKD4 and FASTKD5 and with their combined double knockout. Comprehensive mitochondrial transcriptome analyses of these cell lines revealed a defect in processing at several canonical and non-canonical RNA junctions, accompanied by an increase in specific antisense transcripts. Loss of FASTKD5 led to the most severe phenotype with marked defects in mitochondrial translation of key components of the electron transport chain complexes and in oxidative phosphorylation. We reveal that the FASTK protein family members are crucial regulators of non-canonical junction and non-coding mitochondrial RNA processing. Author summary As a legacy of their bacterial origin, mitochondria have retained their own genome with a unique gene expression system. All mitochondrially encoded proteins are essential components of the respiratory chain. Therefore, the mitochondrial gene expression is crucial for their iconic role as the ‘powerhouse of the cell’–ATP synthesis through oxidative phosphorylation. Consistently, defects in enzymes involved in this gene expression system are a common source of incurable inherited metabolic disorders, called mitochondrial diseases. The human mitochondrial transcription generates long polycistronic transcripts that carry information for multiple genes, so that the expression level of each gene is mainly regulated through post-transcriptional events. The polycistronic transcript first undergoes RNA processing, where individual mRNA, rRNA, and tRNA are cleaved off. However, its entire molecular mechanism remains unclear, and in particular, ‘non-canonical’ RNA processing has been poorly understood. To address this question, we studied the FASTK family proteins, emerging key mitochondrial post-transcriptional regulators. We generated different human cell lines carrying single or combined disruption of FASTKD3, FASTKD4, and FASTKD5 genes, and analyzed them using biochemical and genetic approaches. We show that the FASTK family members fine-tune the processing of both ‘canonical’ and ‘non-canonical’ mitochondrial RNA junctions.

Summary: Advances in omics technologies have generated exponentially larger volumes of biological data; however, their analyses and interpretation are limited to computationally proficient scientists. We created OmicsVolcano, an interactive open-source software tool to enable visualization and exploration of high-throughput biological data, while highlighting features of interest using a volcano plot interface. In contrast to existing tools, our software and user-interface design allow it to be used without requiring any programming skills to generate high-quality and presentation-ready images.

Abstract Background Prioritisation of gene ontology terms from differential gene expression analyses in a two-dimensional format remains a challenge with exponentially growing data volumes. Typically, gene ontology terms are represented as tree-maps that enclose all data into defined space. However, large datasets make this type of visualisation appear cluttered and busy, and often not informative as some labels are omitted due space limits, especially when published in two-dimensional (2D) figures. Results Here we present an open source CirGO (Circular Gene Ontology) software that visualises non-redundant two-level hierarchically structured ontology terms from gene expression data in a 2D space. Gene ontology terms based on statistical significance were summarised with a semantic similarity algorithm and grouped by hierarchical clustering. This software visualises the most enriched gene ontology terms in an informative, comprehensive and intuitive format that is achieved by organising data from the most relevant to the least, as well as the appropriate use of colours and supporting information. Additionally, CirGO is an easy to use software that supports researchers with little computational background to present their gene ontology data in a publication ready format. Conclusions Our easy to use open source CirGO Python software package provides biologists with a succinct presentation of terms and functions that are most represented in a specific gene expression data set in a visually appealing 2D format (e.g. for reporting research results in scientific articles). CirGO is freely available at https://github.com/IrinaVKuznetsova/CirGO.git.

Pentatricopeptide repeat proteins bind single-stranded RNA and have been used to study ssRNA biology. Here the authors co-opt these proteins to target ssDNA and demonstrate specific binding of telomere sequences, the structural basis for ssDNA wrapping, and use them as potent telomerase inhibitors.

Summary: The regulation of mitochondrial RNA life cycles and their roles in ribosome biogenesis and energy metabolism are not fully understood. We used CRISPR/Cas9 to generate heart- and skeletal-muscle-specific knockout mice of the pentatricopeptide repeat domain protein 1, PTCD1, and show that its loss leads to severe cardiomyopathy and premature death. Our detailed transcriptome-wide and functional analyses of these mice enabled us to identify the molecular role of PTCD1 as a 16S rRNA-binding protein essential for its stability, pseudouridylation, and correct biogenesis of the mitochondrial large ribosomal subunit. We show that impaired mitoribosome biogenesis can have retrograde signaling effects on nuclear gene expression through the transcriptional activation of the mTOR pathway and upregulation of cytoplasmic protein synthesis and pro-survival factors in the absence of mitochondrial translation. Taken together, our data show that impaired assembly of the mitoribosome exerts its consequences via differential regulation of mitochondrial and cytoplasmic protein synthesis. : Perks et al. engineered intron-exon boundaries using CRISPR/Cas9 to conditionally knock out Ptcd1 in mice. The RNA-binding protein PTCD1 is essential for heart function and regulates the stability and maturation of the 16S rRNA. PTCD1 is required for mitoribosome biogenesis, mitochondrial function, and coordinated nuclear transcription. Keywords: RNA, cardiomyopathy, regulatory RNAs, RNA-seq, mitochondrial ribosome, RNA-binding proteins, mitochondria, mitochondrial gene expression, ribosome biogenesis

It has been debated whether premature ageing in mitochondrial DNA mutator mice is driven by point mutations or deletions of mtDNA. Matic et al generate Mgme1 knockout mice and show here that these mice have tissue-specific replication stalling and accumulate deleted mtDNA, without developing progeria.

Introduction Musculoskeletal disorders (MSDs) are one of the most common types of work-related diseases that affect health workers, especially dentists. The aim of our study was to examine the presence of musculoskeletal disorders among dentists at the university dental clinic in correlation with risk factors. Materials and methods A questionnaire survey was carried out among 78 dental practitioners aged between 20 to 60 years old, employed at the university dental clinic. Questions included data on physical and psychosocial workload, perceived general health and occurrence of musculoskeletal complaints in the past 12 months, chronic complaints, frequency and length of breaks, exercising habits as well as medical care seeking. Results Pain in the back, neck and shoulders (84.6% / 85.9%) was the most common complaint among the majority of respondents, while reduced range of movement was noticed among significantly fewer subjects, mostly between 40-60 years of age. Prolonged statistic position was considered to be one of the main causes of MSDs (82.05%) while 73.08% of respondents stated at least two more reasons beside this one. Conclusion The percentage of MSDs prevalence among dentists in public health sector is high. More extensive surveys should be undertaken to cover larger group of dentists from both private and public sector, in order to obtain complete analysis of the prevalence of occupational disorders in our country.

The mitochondrial genome, being compressed to 16 kb, is an attractive model system to investigate how RNA-binding proteins chaperone mRNA lifecycles. Here the authors use RNase footprinting and PAR-CLIP to show that the LRPPRC–SLIRP complex stabilizes mRNA structures to expose sites required for translation and polyadenylation.

The influence of environmental insults on the onset and progression of mitochondrial diseases is unknown. To evaluate the effects of infection on mitochondrial disease we used a mouse model of Leigh Syndrome, where a missense mutation in the Taco1 gene results in the loss of the translation activator of cytochrome c oxidase subunit I (TACO1) protein. The mutation leads to an isolated complex IV deficiency that mimics the disease pathology observed in human patients with TACO1 mutations. We infected Taco1 mutant and wild-type mice with a murine cytomegalovirus and show that a common viral infection exacerbates the complex IV deficiency in a tissue-specific manner. We identified changes in neuromuscular morphology and tissue-specific regulation of the mammalian target of rapamycin pathway in response to viral infection. Taken together, we report for the first time that a common stress condition, such as viral infection, can exacerbate mitochondrial dysfunction in a genetic model of mitochondrial disease.

Esthetic and minimally invasive restorative techniques are current topics in dentistry. Introduction of modern composite materials and adhesive technology provided numerous options for design of esthetic restorations without invasive teeth preparation common for traditional prostodontic restorations. Modern esthetic dentistry can provide solutions for simple as well as complex cases by implementation of various alternatives.

The regulation of mitochondrial RNA processing and its importance for ribosome biogenesis and energy metabolism are not clear. We generated conditional knockout mice of the endoribonuclease component of the RNase P complex, MRPP3, and report that it is essential for life and that heart and skeletal-muscle-specific knockout leads to severe cardiomyopathy, indicating that its activity is non-redundant. Transcriptome-wide parallel analyses of RNA ends (PARE) and RNA-seq enabled us to identify that in vivo 5′ tRNA cleavage precedes 3′ tRNA processing, and this is required for the correct biogenesis of the mitochondrial ribosomal subunits. We identify that mitoribosomal biogenesis proceeds co-transcriptionally because large mitoribosomal proteins can form a subcomplex on an unprocessed RNA containing the 16S rRNA. Taken together, our data show that RNA processing links transcription to translation via assembly of the mitoribosome.

Aim To determine frequency and type of thyroid cancer (TC) as well as gender and age distribution of patients operated at the Department of Ear, Nose and Throat (ENT), Cantonal Hospital Zenica, Bosnia and Herzegovina. Methods A retrospective analysis of data obtained from an operating protocol and disease history of patients operated in the eightyear period (2007- 2014) was made according to the frequency and type of thyroid cancer, as well as age and gender of the patients. χ2 test was used for statistical with p˂0.05. Results A total of 818 surgeries of the thyroid gland were conducted, in 714 (87.29%) female and 104 (12.71%) male patients. Malignancies were diagnosed in 74 (9.05%) patients, of whom 64 (86.49%) were females and 10 (13.51%) were males, resulting in the gender prevalence of 8.96% and 9.62%, respectively. The most often presented type was papillary carcinoma, in 48 (out of 74, 64.86%) patients, followed by follicular carcinoma in 10 (13.51%), medullary carcinoma in four (5.41%), Hurthle cell carcinoma in four (5.41%) patients, while anaplastic carcinoma was found in one (1.35%) patient. The number of diagnosed malignancy varied from 0% (in 2007) to 13.91% (in 2014) (p=0.05). Conclusion The prevalence of thyroid cancer is low, but has an increasing trend. A large number of unnecessary surgeries on thyroid gland was performed. Preoperative diagnostic procedures for diseases of the thyroid gland in Cantonal Hospital Zenica should be improved in order to avoid unessential surgeries.

Mutations in the translational activator of cytochrome c oxidase subunit I (TACO1) causes cytochrome c oxidase deficiency and Leigh Syndrome in patients. Here, the authors characterize mice with a mutation that causes lack of TACO1 expression, identifying a mouse model that could be useful for preclinical trials.

Heterozygous mice (αMHC403/+) expressing the human disease-causing mutation Arg403Gln exhibit cardinal features of hypertrophic cardiomyopathy (HCM) including hypertrophy, myocyte disarray, and increased myocardial fibrosis. Treatment of αMHC403/+mice with the L-type calcium channel (ICa-L) antagonist diltiazem has been shown to decrease left ventricular anterior wall thickness, cardiac myocyte hypertrophy, disarray, and fibrosis. However, the role of the ICa-L in the development of HCM is not known. In addition to maintaining cardiac excitation and contraction in myocytes, the ICa-L also regulates mitochondrial function through transmission of movement of ICa-L via cytoskeletal proteins to mitochondrial voltage-dependent anion channel. Here, the authors investigated the role of ICa-L in regulating mitochondrial function in αMHC403/+mice. Whole-cell patch clamp studies showed that ICa-L current inactivation kinetics were significantly increased in αMHC403/+cardiac myocytes, but that current density and channel expression were similar to wild-type cardiac myocytes. Activation of ICa-L caused a significantly greater increase in mitochondrial membrane potential and metabolic activity in αMHC403/+. These increases were attenuated with ICa-L antagonists and following F-actin or β-tubulin depolymerization. The authors observed increased levels of fibroblast growth factor-21 in αMHC403/+mice, and altered mitochondrial DNA copy number consistent with altered mitochondrial activity and the development of cardiomyopathy. These studies suggest that the Arg403Gln mutation leads to altered functional communication between ICa-L and mitochondria that is associated with increased metabolic activity, which may contribute to the development of cardiomyopathy. ICa-L antagonists may be effective in reducing the cardiomyopathy in HCM by altering metabolic activity.

This year as well, the Institute of Special education and rehabilitation celebrated the International day of persons with disabilities. In that occasion, two different events were organized by the Institute at the Faculty of Philosophy. The first event was held on 03.12.2015 and was organized in collaboration with the students of the Institute of Special education and rehabilitation, Faculty of pedagogy “St. Kliment Ohridski” form Skopje, Faculty of architecture, Faculty of Fine Arts and Faculty of Music. In the official part of the program, speeches were held by Stefani Nakova, student at the Institute of Special Education and rehabilitation, dr. Zora Jachova, PhD, head of the Institute of special education and rehabilitation and dr. Velimir Stojkovski, PhD, rector of the University “Ss Cyril and Methodius” – Skopje. Beside the mentioned speeches, the event was enriched by the students from the Faculty of pedagogy “St. Kliment Ohridski” from Skopje with the performance of “Tajno moja” in sign language by Dzengis Memedovski and the presentation of Aleksandar Matovski called “Youth and the Down syndrome”.

Dysfunction of the oxidative phosphorylation (OXPHOS) system is a major cause of human disease and the cellular consequences are highly complex. Here, we present comparative analyses of mitochondrial proteomes, cellular transcriptomes and targeted metabolomics of five knockout mouse strains deficient in essential factors required for mitochondrial DNA gene expression, leading to OXPHOS dysfunction. Moreover, we describe sequential protein changes during post-natal development and progressive OXPHOS dysfunction in time course analyses in control mice and a middle lifespan knockout, respectively. Very unexpectedly, we identify a new response pathway to OXPHOS dysfunction in which the intra-mitochondrial synthesis of coenzyme Q (ubiquinone, Q) and Q levels are profoundly decreased, pointing towards novel possibilities for therapy. Our extensive omics analyses provide a high-quality resource of altered gene expression patterns under severe OXPHOS deficiency comparing several mouse models, that will deepen our understanding, open avenues for research and provide an important reference for diagnosis and treatment.

Human mitochondrial DNA is transcribed as long polycistronic transcripts that encompass each strand of the genome and are processed subsequently into mature mRNAs, tRNAs, and rRNAs, necessitating widespread posttranscriptional regulation. Here, we establish methods for massively parallel sequencing and analyses of RNase-accessible regions of human mitochondrial RNA and thereby identify specific regions within mitochondrial transcripts that are bound by proteins. This approach provides a range of insights into the contribution of RNA-binding proteins to the regulation of mitochondrial gene expression.

We have studied the in vivo role of SLIRP in regulation of mitochondrial DNA (mtDNA) gene expression and show here that it stabilizes its interacting partner protein LRPPRC by protecting it from degradation. Although SLIRP is completely dependent on LRPPRC for its stability, reduced levels of LRPPRC persist in the absence of SLIRP in vivo. Surprisingly, Slirp knockout mice are apparently healthy and only display a minor weight loss, despite a 50-70% reduction in the steady-state levels of mtDNA-encoded mRNAs. In contrast to LRPPRC, SLIRP is dispensable for polyadenylation of mtDNA-encoded mRNAs. Instead, deep RNA sequencing (RNAseq) of mitochondrial ribosomal fractions and additional molecular analyses show that SLIRP is required for proper association of mRNAs to the mitochondrial ribosome and efficient translation. Our findings thus establish distinct functions for SLIRP and LRPPRC within the LRPPRC-SLIRP complex, with a novel role for SLIRP in mitochondrial translation. Very surprisingly, our results also demonstrate that mammalian mitochondria have a great excess of transcripts under basal physiological conditions in vivo.

On December 2nd 2016 in the main amphitheater at the Faculty of Philosophy in Skopje, was held the celebration of December 3rd, the International Day of Persons with Disabilities, in organization of the Institute of Special Education and Rehabilitation. The official part of the program was started with a speech by Goran Ajdinski, PhD, the Dean of the Faculty of Philosophy in Skopje. The guests at the celebration were also greeted by the Rector of the University “Ss. Cyril and Methodius” – Skopje, Nikola Jankulovski, PhD and the Minister of Labor and Social Policy of Republic of Macedonia, Frosina Tashevska-Remenski, PhD. After the speeches, which highlighted the current efforts and future commitment to inclusion and accessibility of persons with disabilities, two awards were presented by the Humanitarian foundation “Prof. d-r Ljupco Ajdinski”. The first award was given to Simona Kostadinova as the student with achieved highest grade point average of 9.65 in the generation 2011/12 during the studies of Special education and rehabilitation. The second award was intended for the highest ranked student at the university admission in 2016/2017. This award belonged to Nadica Gjerasimova who had 97.70 points on the official rank list. Beside the awards, two acknowledgements for humanity were also given by the Foundation “Prof. d-r Ljupco Ajdinski”. For the longstanding human activity in preparation of special education and rehabilitation staff and education and rehabilitation of persons with disabilities, the first acknowledgement was given to the Institute of Special education and rehabilitation. The second acknowledgement was meant for Kiril Temkov, PhD, about his numerous initiated and organized human activities, especially for the published paper on the ethical dimensions of special education and rehabilitation and introduction of Ethics in the education system in Republic of Macedonia. The last part of the program was intended for cultural and art performances of the students from special and regular schools and institutions for education and rehabilitation in the country. In this part of the celebration, the students from the Institute for Rehabilitation of Children and Youth-Skopje took part by poetry reading, the students form DUCOR “Partenija Zografski” performed a dance on music from Michael Jackson, and the students from the elementary school “Vlado Taseski” had a music performance of two songs with sign language translation. The program was enriched with the ballet performance of the students from the special school “Idnina” and the students from DURDMOV “Dimitar Vlahov” had two music performances, vocal and instrumental. The program was completed with a folklore dance of the students from the Center for rehabilitation of children with impaired hearing, speech and voice and other development problems “Kocho Racin” – Bitola.

The evolutionary divergence of mitochondrial ribosomes from their bacterial and cytoplasmic ancestors has resulted in reduced RNA content and the acquisition of mitochondria-specific proteins. The mitochondrial ribosomal protein of the small subunit 34 (MRPS34) is a mitochondria-specific ribosomal protein found only in chordates, whose function we investigated in mice carrying a homozygous mutation in the nuclear gene encoding this protein. The Mrps34 mutation causes a significant decrease of this protein, which we show is required for the stability of the 12S rRNA, the small ribosomal subunit and actively translating ribosomes. The synthesis of all 13 mitochondrially-encoded polypeptides is compromised in the mutant mice, resulting in reduced levels of mitochondrial proteins and complexes, which leads to decreased oxygen consumption and respiratory complex activity. The Mrps34 mutation causes tissue-specific molecular changes that result in heterogeneous pathology involving alterations in fractional shortening of the heart and pronounced liver dysfunction that is exacerbated with age. The defects in mitochondrial protein synthesis in the mutant mice are caused by destabilization of the small ribosomal subunit that affects the stability of the mitochondrial ribosome with age.

Traditionally, this year as well, during the period from 7th to 9th November 2014, the 8-th International scientific conference “Special education and rehabilitation today” was held at the Faculty of Special Education and Rehabilitation in Belgrade, Republic of Serbia,. During the three conference days, many papers were presented by reputable researchers and practitioners form Republic of Serbia, but also form the abroad countries Montenegro, Croatia, Bosnia and Herzegovina, Slovenia, Macedonia, Russia, Italy and Greece. All paper presentations were separated in the following fields, according to which the conference sessions were organized: Assessment techniques in special education and rehabilitation; Forms of treatment in special education and rehabilitation; Behavioral disorders, delinquency, addictive behavior and crime: prevention and early intervention; Behavioral disorders, delinquency, addictive behavior and crime: treatment and relapse prevention; Education of persons with disabilities and developmental disorders; Quality of life of persons with disabilities.