A detailed description of the distress trajectory from pre- to post-treatment in breast cancer patients receiving neoadjuvant chemotherapy.

PURPOSE: To characterize the distress trajectory in patients with newly diagnosed, non-metastatic breast cancer from pre-neoadjuvant chemotherapy until 12 months after onset of treatment and to identify demographic and clinical predictors of distress in these patients. METHODS: In a retrospective, longitudinal study, chart review data were abstracted for 252 eligible patients treated at a comprehensive cancer care center. The center screens for distress at least monthly with the distress thermometer; the highest distress score per month was included in the analyses. The growth trajectory was established using mixed modeling and predictors were added to the initial growth model in subsequent models. RESULTS: Distress showed a cubic growth trajectory with highest distress prior to treatment onset followed by a steep decline in the first three months of treatment. A slight increase in distress was apparent over months 6-10. Being Hispanic was associated with a stronger increase in distress in the second half of the year (p = 0.012). NACT was associated with lower distress and surgery with higher distress (both: p < 0.001). CONCLUSION: Distress is at its peak prior to treatment onset and rapidly decreases once treatment has started. Oncologist should be aware that both completion of NACT and undergoing surgery are associated with increases in distress and Hispanic patients may be more at risk for an increase in distress at these times; this suggests that careful monitoring of distress during the treatment trajectory and in Hispanic patients in particular in order to provide timely support.

Gene modification by fast-track recombineering for cellular localization and isolation of components of plant protein complexes.

To accelerate the isolation of plant protein complexes and study cellular localization and interaction of their components, an improved recombineering protocol is described for simple and fast site-directed modification of plant genes in bacterial artificial chromosomes (BACs). Coding sequences of fluorescent and affinity tags were inserted into genes and transferred together with flanking genomic sequences of desired size by recombination into Agrobacterium plant transformation vectors using three steps of E. coli transformation with PCR-amplified DNA fragments. Application of fast-track recombineering is illustrated by the simultaneous labelling of CYCLIN-DEPENDENT KINASE D (CDKD) and CYCLIN H (CYCH) subunits of kinase module of TFIIH general transcription factor and the CDKD-activating CDKF;1 kinase with green fluorescent protein (GFP) and mCherry (green and red fluorescent protein) tags, and a PIPL (His18 -StrepII-HA) epitope. Functionality of modified CDKF;1 gene constructs is verified by complementation of corresponding T-DNA insertion mutation. Interaction of CYCH with all three known CDKD homologues is confirmed by their co-localization and co-immunoprecipitation. Affinity purification and mass spectrometry analyses of CDKD;2, CYCH, and DNA-replication-coupled HISTONE H3.1 validate their association with conserved TFIIH subunits and components of CHROMATIN ASSEMBLY FACTOR 1, respectively. The results document that simple modification of plant gene products with suitable tags by fast-track recombineering is well suited to promote a wide range of protein interaction and proteomics studies.

[Areas and challenges of oncopsychological rehabilitation]. / Az onkopszichológiai rehabilitáció területei és kihívásai.

Patients with cancer present a number of different difficulties that adversely affect their health care and recovery (e.g. poor communication with physicians, lack of knowledge about their illness and its management, financial problems). Furthermore, mental health problems, such as distress, depression and anxiety, are common amongst patients with cancer. These mental health problems are additional contributors to functional impairment in carrying out family, work, and other social roles, poor adherence to medical treatments, and adverse medical outcomes. Oncopsychosocial rehabilitation aims to optimize the possibilities of medical health care through psychological interventions by helping cancer patients and their families and/or health care workers with the management of the psychological and social aspects of the illness. Oncopsychosocial rehabilitation includes all psychosocial interventions that are designed to positively influence patient psychosocial adaptation and adjustment to diagnosis, treatment, and survivorship. Oncopsychological rehabilitation could also manage cancer related distress and other psychosocial problems with specific types of treatments or interventions including prevention, relaxation techniques, structured psychoeducational interventions including sexual information and/or preparation for surgery, and various methods of psychotherapy.

[Breast cancer: patient care, rehabilitation, psychooncology]. / Emlõrák: gondozás, rehabilitáció, pszichoonkológia.

The development of a recommendation was intended for the follow-up of breast cancer patients treated with curative intent in Hungary. Follow-up includes the permanent contact with and health education of the patient, the surveillance and control of the adverse effects of oncological therapies or radiotherapy, the screening of metachron cancers, and the comprehensive (physical, psychological and social) rehabilitation of the patient. The early detection of local/regional tumor relapse is essential with careful follow-up, but there is no need for screening of distant metastases by means of imaging studies or tumor marker tests. If adjuvant endocrine therapy is needed, optimal adherence should be ensured with supportive therapy. In rare cases, special issues such as breast cancer risk/genetic mutation, pregnancy are raised, which should be thoughtfully discussed in view of recent advances in oncology. Follow-up is generally practised by the oncologist, however, in some cases the social worker, the physiotherapist, the psychooncologist, or in special cases, the lymphoedema expert is to be involved. The follow-up approach should be comprehensive and holistic.

CDKF;1 and CDKD protein kinases regulate phosphorylation of serine residues in the C-terminal domain of Arabidopsis RNA polymerase II.

Phosphorylation of conserved Y1S2P3T4S5P6S7 repeats in the C-terminal domain of largest subunit of RNA polymerase II (RNAPII CTD) plays a central role in the regulation of transcription and cotranscriptional RNA processing. Here, we show that Ser phosphorylation of Arabidopsis thaliana RNAPII CTD is governed by CYCLIN-DEPENDENT KINASE F;1 (CDKF;1), a unique plant-specific CTD S7-kinase. CDKF;1 is required for in vivo activation of functionally redundant CYCLIN-DEPENDENT KINASE Ds (CDKDs), which are major CTD S5-kinases that also phosphorylate in vitro the S2 and S7 CTD residues. Inactivation of CDKF;1 causes extreme dwarfism and sterility. Inhibition of CTD S7-phosphorylation in germinating cdkf;1 seedlings is accompanied by 3'-polyadenylation defects of pre-microRNAs and transcripts encoding key regulators of small RNA biogenesis pathways. The cdkf;1 mutation also decreases the levels of both precursor and mature small RNAs without causing global downregulation of the protein-coding transcriptome and enhances the removal of introns that carry pre-microRNA stem-loops. A triple cdkd knockout mutant is not viable, but a combination of null and weak cdkd;3 alleles in a triple cdkd123* mutant permits semidwarf growth. Germinating cdkd123* seedlings show reduced CTD S5-phosphorylation, accumulation of uncapped precursor microRNAs, and a parallel decrease in mature microRNA. During later development of cdkd123* seedlings, however, S7-phosphorylation and unprocessed small RNA levels decline similarly as in the cdkf;1 mutant. Taken together, cotranscriptional processing and stability of a set of small RNAs and transcripts involved in their biogenesis are sensitive to changes in the phosphorylation of RNAPII CTD by CDKF;1 and CDKDs.

Perioperative attitudes of breast cancer patients towards the complementary and alternative medicine based on a survey conducted at the National Institute of Oncology in Hungary. / Emlorákban megbetegedett nok perioperatív viszonyulása a komplementer és alternatív medicinához az Országos Onkológiai Intézetben végzett felmérés alapján.

Összefoglaló. Bevezetés: A komplementer és alternatív medicina (KAM) egyre népszerubb a daganatos betegek körében világszerte. Az emlorákkal diagnosztizált nok 45%-a használ KAM-ot, a fiatalabb betegek 62,5%-a. Magyarországon eddig egyetlen tanulmány jelent meg a témában, mely szerint a magyar, emlodaganattal küzdo nok 84,4%-a használ valamilyen komplementer terápiát. Egyes KAM-modalitások alkalmazása a gyógyszerkölcsönhatások miatt kockázatot hordoz. Fontos megismernünk a magyar páciensek igényeit és szokásait a KAM-használattal kapcsolatban, mely ismeret a klinikai gyakorlatban közvetlenül hasznosítható. Célkituzés: Vizsgálatunk célja a magyar emlorákos nok körében felmérni a KAM alkalmazásának mértékét, megvizsgálni ennek okait és az ezzel összefüggo demográfiai, pszichológiai és klinikai faktorokat. Módszer: Kérdoíves vizsgálatunkat az Országos Onkológiai Intézet Emlo- és Lágyrészsebészeti Osztályán végeztük az osztályon bent fekvok körében (n = 146). Felmértük a szociodemográfiai adatokat, a KAM-használat jellemzoit, a KAM iránti attitudöt és az egészségkontroll-igényt. A kérdoív adatait klinikai adatokkal egészítettük ki. Eredmények: A válaszadók 36%-a felkeresett KAM-szolgáltatót, 71%-a használ KAM-készítményt, és 64%-a alkalmaz önsegíto gyakorlatot. Ezekrol a betegek többsége egészségügyi szakembertol tájékozódik. A mintában a holisztikus szemlélet, valamint a belso és a társas külso kontroll dominál. A KAM-szolgáltatókat felkeresoknek és a KAM-készítményt alkalmazóknak erosebb a belsokontroll-igényük. A KAM-szolgáltatást vagy önsegíto gyakorlatot alkalmazók kedvezobben ítélik meg saját egészségi állapotukat. Következtetés: A betegeknek a számukra fontos személyektol, elsosorban a kezeloszemélyzettol kapott információ dönto az egészségükkel kapcsolatos viselkedésben, közöttük a KAM-választásban. Fontos látnunk a páciensek nagyfokú bizalmát az egészségügyi szakemberek iránt és eros igényét a KAM-mal kapcsolatos információk megbeszélésére, valamint az egészségük iránt érzett felelosségvállalásra és a kezelésben való aktív részvételre. Orv Hetil. 2022; 163(9): 350-361. INTRODUCTION: The popularity of complementary and alternative medicine (CAM) is increasing among cancer patients worldwide. 45% of women diagnosed with breast cancer use CAM, 62.5% of younger patients do so. So far, only one study has been published in Hungary, according to which 84.4% of Hungarian women with breast cancer use some form of complementary medicine. The utilization of some CAM modalities carries risks due to drug interactions. It is important to get to know the needs and habits of Hungarian patients in relation to CAM, which knowledge can be directly used in clinical practice. OBJECTIVE: The aim of our study was to assess the extent of CAM utilization among Hungarian breast cancer patients, to examine the reasons behind this choice, and to see the relating/connecting demographic, psychological and clinical factors. METHOD: In a cross-sectional survey, a self-administered questionnaire was used among inpatients at the Department of Breast and Soft Tissue Surgery in the National Institute of Oncology (n = 146). We assessed socio-demographic data, characteristics of CAM use, attitudes toward CAM, and the need for health control. Clinical data were added to the questionnaire data. RESULTS: 36% of the respondents visited some CAM providers, 71% used CAM preparation and 64% utilized self-help practices. Most patients are informed about these by a healthcare professional. The holistic approach is dominant in the sample as well as internal and social external control. Visitors to CAM providers and CAM preparation users have a stronger need for internal control. Visitors to CAM providers and self-help practitioners judge their own health status more favorable. CONCLUSION: The information that patients receive from people who are important to them, especially the caregiver, is crucial in their health-related behavior, including the choice of CAM. It is important to see such a high level of patient trust in health professionals and a strong need to discuss information about CAM, as well as a sense of responsibility for their health and active participation in treatment. Orv Hetil. 2022; 163(9): 350-361.

Breast Cancer Survivorship Programme: Follow-Up, Rehabilitation, Psychosocial Oncology Care. 1st Central-Eastern European Professional Consensus Statement on Breast Cancer.

Follow-up includes ongoing contact with and health education of the patient, surveillance and control of the adverse effects of surgery, oncological therapies or radiotherapy, screening of metachronous cancers, and comprehensive (physical, psychological and social) patient rehabilitation, which may be enhanced by a healthy lifestyle. Primary attention should be paid to early detection and, when needed, curative treatment of local/regional tumour recurrences. Similarly, with the hope of curative solution, it is important to recognize the entity of a low-mass and relatively indolent recurrence or metastasis (oligometastasis); however, there is still no need to investigate distant metastases by routine diagnostic imaging or assess tumour markers. Below there is a list of possible sources of support, with respect to adjuvant hormone therapy continued during long-term care, social support resources, pivotal points and professional opportunities for physical and mental rehabilitation. Individual solutions for specific issues (breast cancer risk/genetic mutation, pregnancy) are provided by constantly widening options. Ideally, a complex breast cancer survivorship programme is practised by a specially trained expert supported by a cooperative team of oncologists, surgeons, breast radiologists, social workers, physiotherapists, psycho-oncologists and psychiatrists. The approach of follow-up should be comprehensive and holistic.

Transcriptional control of aspartate kinase expression during darkness and sugar depletion in Arabidopsis: involvement of bZIP transcription factors.

Initial steps of aspartate-derived biosynthesis pathway (Asp pathway) producing Lys, Thr, Met and Ile are catalyzed by bifunctional (AK/HSD) and monofunctional (AK-lys) aspartate kinase (AK) enzymes. Here, we show that transcription of all AK genes is negatively regulated under darkness and low sugar conditions. By using yeast one-hybrid assays and complementary chromatin immunoprecipitation analyses in Arabidopsis cells, the bZIP transcription factors ABI5 and DPBF4 were identified, capable of interacting with the G-box-containing enhancer of AK/HSD1 promoter. Elevated transcript levels of DPBF4 and ABI5 under darkness and low sugar conditions coincide with the repression of AK gene expression. Overexpression of ABI5, but not DPBF4, further increases this AK transcription suppression. Concomitantly, it also increases the expression of asparagines synthetase 1 (ASN1) that shifts aspartate utilization towards asparagine formation. However, in abi5 or dpbf4 mutant and abi5, dpbf4 double mutant the repression of AK expression is maintained, indicating a functional redundancy with other bZIP-TFs. A dominant-negative version of DPBF4 fused to the SRDX repressor domain of SUPERMAN could counteract the repression and stimulate AK expression under low sugar and darkness in planta. This effect was verified by showing that DPBF4-SRDX fails to recognize the AK/HSD1 enhancer sequence in yeast one-hybrid assays, but increases heterodimmer formation with DPBF4 and ABI5, as estimated by yeast two-hybrid assays. Hence it is likely that heterodimerization with DPBF4-SRDX inhibits the binding of redundantly functioning bZIP-TFs to the promoters of AK genes and thereby releases the repressing effect. These data highlight a novel transcription control of the chloroplast aspartate pathway that operates under energy limiting conditions.

[Breast cancer: follow-up, rehabilitation, psycho- oncology]. / Emlorák: gondozás, rehabilitáció, pszichoonkológia Ajánlás a IV. Emlorák Konszenzus Konferencia alapján.

Follow-up includes the permanent contact with and health education of the patient, the surveillance and control of the adverse effects of surgery, oncological therapies or radiotherapy, the screening of metachronous cancers, and the comprehensive (physical, psychological and social) rehabilitation of the patient which may be enhanced by healthy life-style. The early detection and curative management if necessary, of local/regional tumor relapse is still a priority but the routine screening of distant metastases by means of imaging studies or tumor marker tests is not justified. Supportive therapy means to endocrine therapy, available social support in Hungary, and the key issues and managing tools of physical and psychooncological care are provided. Individual solution of special issues (breast cancer risk/genetic mutation, pregnancy) may be served by widening options. Ideally, follow-up is practised by a cooperative team of oncologists, surgeons, breast radiologists, social workers, physiotherapists, psychiatrists. The follow-up approach should be comprehensive and holistic.

"Clicks, likes, shares and comments" a systematic review of breast cancer screening discourse in social media.

BACKGROUND: Unsatisfactory participation rate at population based organised breast cancer screening is a long standing problem. Social media, with 3.2 billion users in 2019, is potentially an important site of breast cancer related discourse. Determining whether these platforms might be used as channels by screening providers to reach under-screened women may have considerable public health significance. OBJECTIVES: By systematically reviewing original research studies on breast cancer related social media discourse, we had two aims: first, to assess the volume, participants and content of breast screening social media communication and second, to find out whether social media can be used by screening organisers as a channel of patient education. METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). After searching PubMed, ScienceDirect, Web of Science, Springer and Ebsco, 17 studies were found that met our criteria. A systematic narrative framework was used for data synthesis. Owing to the high degree of heterogeneity in social media channels, outcomes and measurement included in this study, a meta-analytic approach was not appropriate. RESULTS: The volume of breast cancer related social media discourse is considerable. The majority of participants are lay individuals as opposed to healthcare professionals or advocacy groups. The lay misunderstandings surrounding the harms and benefits of mammography is well mirrored in the content of social media discourse. Although there is criticism, breast cancer screening sentiment on the social media ranges from the neutral to the positive. Social media is suitable for offering peer emotional support for potential participants. CONCLUSION: Dedicated breast screening websites operated by screening organisers would ensure much needed quality controlled information and also provide space for reliable question and answer forums, the sharing of personal experience and the provision of peer and professional support.

SELENOPROTEIN O is a chloroplast protein involved in ROS scavenging and its absence increases dehydration tolerance in Arabidopsis thaliana.

The evolutionary conserved family of Selenoproteins performs redox-regulatory functions in bacteria, archaea and eukaryotes. Among them, members of the SELENOPROTEIN O (SELO) subfamily are located in mammalian and yeast mitochondria, but their functions are thus far enigmatic. Screening of T-DNA knockout mutants for resistance to the proline analogue thioproline (T4C), identified mutant alleles of the plant SELO homologue in Arabidopsis thaliana. Absence of SELO resulted in a stress-induced transcriptional activation instead of silencing of mitochondrial proline dehydrogenase, and also high elevation of Δ(1)-pyrroline-5-carboxylate dehydrogenase involved in degradation of proline, thereby alleviating T4C inhibition and lessening drought-induced proline accumulation. Unlike its animal homologues, SELO was localized to chloroplasts of plants ectopically expressing SELO-GFP. The protein was co-fractionated with thylakoid membrane complexes, and co-immunoprecipitated with FNR, PGRL1 and STN7, all involved in regulating PSI and downstream electron flow. The selo mutants displayed extended survival under dehydration, accompanied by longer photosynthetic activity, compared with wild-type plants. Enhanced expression of genes encoding ROS scavenging enzymes in the unstressed selo mutant correlated with higher oxidant scavenging capacity and reduced methyl viologen damage. The study elucidates SELO as a PSI-related component involved in regulating ROS levels and stress responses.

Factor XIII, clot structure, thrombosis.

Blood coagulation factor XIII (FXIII) is a tetrameric protein consisting of two catalytic A (FXIII-A) and two carrier/inhibitory B (FXIII-B) subunits. It is a zymogen, which becomes transformed into an active transglutaminase (FXIIIa) in the final phase of coagulation cascade by thrombin and Ca(2+). FXIII is essential for hemostasis, its deficiency results in severe bleeding diathesis. FXIIIa mechanically stabilizes fibrin by cross-linking its α-, and γ-chains. It also protects newly formed fibrin from fibrinolysis, primarily by cross-linking α(2)-plasmin inhibitor to fibrin. Beside the above prothrombotic effects, it is involved in limiting thrombus growth by down-regulating platelet adhesion to fibrin. Elevated FXIII level seems to be a gender-specific risk factor of both coronary artery disease and peripheral arterial disease, it represents an increased risk only in females. The association of FXIII level with the risk of ischemic stroke and venous thromboembolism was investigated only in a few studies from which no clear conclusion could be drawn. Among the FXIII subunit polymorphisms, concerning their effect on the risk of thrombotic diseases, only FXIII-A p.Val34Leu was investigated extensively. Meta-analyses of reported data suggest that this polymorphism provides a moderate protection against coronary artery disease and venous thromboembolism, but not against ischemic stroke. Gene-gene and gene-environmental interactions might modify its effect. Further studies are required to explore the effect of other FXIII subunit polymorphism on the risk of thrombotic diseases.

The spliceosome-activating complex: molecular mechanisms underlying the function of a pleiotropic regulator.

Correct interpretation of the coding capacity of RNA polymerase II transcribed eukaryotic genes is determined by the recognition and removal of intronic sequences of pre-mRNAs by the spliceosome. Our current knowledge on dynamic assembly and subunit interactions of the spliceosome mostly derived from the characterization of yeast, Drosophila, and human spliceosomal complexes formed on model pre-mRNA templates in cell extracts. In addition to sequential structural rearrangements catalyzed by ATP-dependent DExH/D-box RNA helicases, catalytic activation of the spliceosome is critically dependent on its association with the NineTeen Complex (NTC) named after its core E3 ubiquitin ligase subunit PRP19. NTC, isolated recently from Arabidopsis, occurs in a complex with the essential RNA helicase and GTPase subunits of the U5 small nuclear RNA particle that are required for both transesterification reactions of splicing. A compilation of mass spectrometry data available on the composition of NTC and spliceosome complexes purified from different organisms indicates that about half of their conserved homologs are encoded by duplicated genes in Arabidopsis. Thus, while mutations of single genes encoding essential spliceosome and NTC components lead to cell death in other organisms, differential regulation of some of their functionally redundant Arabidopsis homologs permits the isolation of partial loss of function mutations. Non-lethal pleiotropic defects of these mutations provide a unique means for studying the roles of NTC in co-transcriptional assembly of the spliceosome and its crosstalk with DNA repair and cell death signaling pathways.

Thrombomodulin-dependent effect of factor VLeiden mutation on factor XIII activation.

INTRODUCTION: Factor V Leiden mutation (FV(Leiden)) is associated with impaired down-regulation of activated FV procoagulant activity and loss of FV anticoagulant function that result in an increased risk of venous thromboembolism. As the downstream effects of FV(Leiden) on clot formation and fibrinolyis have only partially been revealed, we investigated its effect on the activation of factor XIII (FXIII) and the cross-linking of fibrin. METHODS: In the plasma samples of fifteen healthy individuals with known FV genotypes coagulation was initiated by recombinant human tissue factor and phospholipids with or without recombinant human thrombomodulin (rhTM). FV deficient plasma supplemented with purified wild type FV or FV(Leiden) were also investigated. Clots were recovered and analyzed by SDS-PAGE and quantitative densitometric evaluation of Western blots. RESULTS: rhTM considerably delayed the activation of FXIII in the plasma from FV wild type individuals. This effect of rhTM was significantly impaired in the plasma from FV(Leiden) carriers. The results were confirmed in experiments with FV deficient plasma supplemented by FV prepared from wild type individuals or FV(Leiden) homozygotes. Fibrin γ-chain dimerization was also considerably delayed by rhTM in plasma samples from individuals without Leiden mutation, but not in plasma samples from FV(Leiden) heterozygotes or homozygotes. The difference between heterozygotes and homozygotes was not statistically significant. CONCLUSION: The highly diminished delaying effect of TM on FXIII activation and on the cross-linking of fibrin in FV(Leiden) carriers might represent a novel mechanism contributing to the increased thrombosis risk of these individuals.

Thrombomodulin-dependent effect of factor V Leiden mutation on the cross-linking of α2-plasmin inhibitor to fibrin and its consequences on fibrinolysis.

INTRODUCTION: It has been shown that thrombomodulin (TM) considerably delays factor XIII (FXIII) activation and this effect is abrogated by Factor V Leiden (FV(Leiden)) mutation. The aim of the study was to explore the effect of TM on the cross-linking of α(2)-plasmin inhibitor (α(2)-PI) to fibrin in plasma samples of different FV genotypes and how this effect is related to the impaired fibrinolysis of FV(Leiden) carriers. METHODS: In the plasma samples of fifteen individuals with different FV genotypes and in FV deficient plasma supplemented with wild type FV or FV(Leiden) coagulation was initiated by recombinant human tissue factor and phospholipids with or without recombinant human TM (rhTM). In the recovered clots the extent of α(2)-PI-fibrin cross-linking was evaluated by Western blotting and quantitative densitometry. The effect of rhTM on tissue plasminogen activator (tPA) induced clot lysis was measured by turbidimetric method. RESULTS: rhTM significantly delayed the formation of α(2)-PI-fibrin α-chain heterodimers/oligomers in plasma samples containing wild type FV. This effect of rhTM was impaired in the presence of FV(Leiden). rhTM delayed tPA-induced clot lysis and this effect of rhTM was more pronounced in plasma containing FV(Leiden). When TAFIa was inhibited by potato carboxypeptidase inhibitor, rhTM accelerated clot lysis in the presence of wild type FV, which is explained by the delayed α(2)-PI-fibrin cross-linking. This effect of rhTM did not prevail in the presence of FV(Leiden). CONCLUSION: FV(Leiden) abrogates the delaying effect of rhTM on α(2)-PI-fibrin cross-linking, which contributes to the impaired fibrinolysis observed in FV(Leiden) carriers.

Arabidopsis PPR40 connects abiotic stress responses to mitochondrial electron transport.

Oxidative respiration produces adenosine triphosphate through the mitochondrial electron transport system controlling the energy supply of plant cells. Here we describe a mitochondrial pentatricopeptide repeat (PPR) domain protein, PPR40, which provides a signaling link between mitochondrial electron transport and regulation of stress and hormonal responses in Arabidopsis (Arabidopsis thaliana). Insertion mutations inactivating PPR40 result in semidwarf growth habit and enhanced sensitivity to salt, abscisic acid, and oxidative stress. Genetic complementation by overexpression of PPR40 complementary DNA restores the ppr40 mutant phenotype to wild type. The PPR40 protein is localized in the mitochondria and found in association with Complex III of the electron transport system. In the ppr40-1 mutant the electron transport through Complex III is strongly reduced, whereas Complex IV is functional, indicating that PPR40 is important for the ubiqinol-cytochrome c oxidoreductase activity of Complex III. Enhanced stress sensitivity of the ppr40-1 mutant is accompanied by accumulation of reactive oxygen species, enhanced lipid peroxidation, higher superoxide dismutase activity, and altered activation of several stress-responsive genes including the alternative oxidase AOX1d. These results suggest a close link between regulation of oxidative respiration and environmental adaptation in Arabidopsis.