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Abstract Background People who have had anterior cruciate ligament reconstruction (ACLR) are at a high risk of developing tibiofemoral joint (TFJ) osteoarthritis (OA), with concomitant meniscal injury elevating this risk. This study aimed to investigate OA-related morphological change over 2 years in the TFJ among individuals who have undergone ACLR with or without concomitant meniscal pathology and in healthy controls. A secondary aim was to examine associations of baseline TFJ cartilage defects and bone marrow lesions (BML) scores with tibial cartilage volume change in ACLR groups. Methods Fifty seven ACLR participants aged 18–40 years (32 isolated ACLR, 25 combined meniscal pathology) underwent knee magnetic resonance imaging (MRI) 2.5 and 4.5 years post-surgery. Nine healthy controls underwent knee MRI at the ~ 2-year intervals. Tibial cartilage volume, TFJ cartilage defects and BMLs were assessed from MRI. Results For both ACLR groups, medial and lateral tibial cartilage volume increased over 2 years (P

Environmental DNA metabarcoding of benthic bacterial communities emerged as a very powerful technology to assess environmental disturbance effects of coastal salmon aquaculture. A prerequisite for the implementation of this approach into compliance monitoring regulations is its robustness and reproducibility of obtained results. In the framework of regular compliance monitoring of a Scottish salmon farm, we therefore collected sediment samples along a transect from the salmon cages to reference sites in duplicates (biological replicates). Aliquots of both biological replicate samples were then processed by two different laboratories using independently the same eDNA metabarcoding protocol (technical replicates). Measures of alpha diversity and beta diversity, as well as taxonomic profiles of benthic bacterial communities were highly congruent among technical replicates, which even showed less variations then the biological replicates that were processed within each laboratory. Both technical replicate datasets identified the same bacterial indicator taxon groups and ASVs that are characteristic for the environmental quality (EQ) categories to which each of the samples was assigned based on traditional macroinvertebrate biomonitoring of the same samples. In a supervised machine learning (SML) approach, we could classify all individual samples from one technical replicate dataset into the correct EQ category using all samples of the other technical replicate dataset as a training dataset for the SML algorithm. We conclude that eDNA metabarcoding is sufficiently robust that different laboratories come to the same conclusions regarding officially regulated action criteria for environmental impact assessments in salmon aquaculture.

Abstract Background The programmed cell death 4 (PDCD4) protein is induced in animals during apoptosis and functions to inhibit translation and tumor promoter-induced neoplastic transformation. PDCD4 is composed of two MA3 domains that share similarity with the single MA3 domain present in the eukaryotic translation initiation factor (eIF) 4G, which serves as a scaffold protein to assemble several initiation factors needed for the recruitment of the 40S ribosomal subunit to an mRNA. Although eIF4A is an ATP-dependent RNA helicase that binds the MA3 domain of eIF4G to promote translation initiation, binding of eIF4A to the MA3 domains of PDCD4 inhibits protein synthesis. Genes encoding PDCD4 are present in many lower eukaryotes and in plants, but PDCD4 in higher plants is unique in that it contains four MA3 domains and has been implicated in ethylene signaling and abiotic stress responses. Here, we examine the evolution of PDCD4 in plants. Results In older algal lineages, PDCD4 contains two MA3 domains similar to the homolog in animals. By the appearance of early land plants, however, PDCD4 is composed of four MA3 domains which likely is the result of a duplication of the two MA3 domain form of the protein. Evidence from fresh water algae, from which land plants evolved, suggests that the duplication event occurred prior to the colonization of land. PDCD4 in more recently evolved chlorophytes also contains four MA3 domains but this may have resulted from an independent duplication event. Expansion and divergence of the PDCD4 gene family occurred during land plant evolution with the appearance of a distinct gene member following the evolution of basal angiosperms. Conclusions The appearance of a unique form of PDCD4 in plants correlates with the appearance of components of the ethylene signaling pathway, suggesting that it may represent the adaptation of an existing protein involved in programmed cell death to one that functions in abiotic stress responses through hormone signaling.

The authors use data from the British Skills and Employment Surveys to document and to try to account for sustained work intensification between 2001 and 2017. They estimate the determinants of work intensity, first using four waves of the pooled cross-section data, then using a constructed pseudo-panel of occupation–industry cells. The latter approach suggests biases in cross-section models of work intensity, associated with unobserved fixed effects in specific occupations and industries. The pseudo-panel analysis can account for slightly more than half (51%) of work intensification using variables that measure effort-biased technological change, effort-biased organizational change, the growing requirement for learning new things, and the rise of self-employment. The authors interpret the work intensification and these effects within a power-resources framework. [ABSTRACT FROM AUTHOR]

Organisms differ in the types and numbers of tRNA genes that they carry. While the evolutionary mechanisms behind tRNA gene set evolution have been investigated theoretically and computationally, direct observations of tRNA gene set evolution remain rare. Here, we report the evolution of a tRNA gene set in laboratory populations of the bacterium Pseudomonas fluorescens SBW25. The growth defect caused by deleting the single-copy tRNA gene, serCGA, is rapidly compensated by large-scale (45–290 kb) duplications in the chromosome. Each duplication encompasses a second, compensatory tRNA gene (serTGA) and is associated with a rise in tRNA-Ser(UGA) in the mature tRNA pool. We postulate that tRNA-Ser(CGA) elimination increases the translational demand for tRNA-Ser(UGA), a pressure relieved by increasing serTGA copy number. This work demonstrates that tRNA gene sets can evolve through duplication of existing tRNA genes, a phenomenon that may contribute to the presence of multiple, identical tRNA gene copies within genomes.

Ethylene, a regulator of plant growth and development, is perceived by specific receptors that act as negative regulators of the ethylene response. Five ethylene receptors, i.e., ETR1, ERS1, EIN4, ETR2, and ERS2, are present in Arabidopsis and dominant negative mutants of each that confer ethylene insensitivity have been reported. In contrast, maize contains just two types of ethylene receptors: ZmERS1, encoded by ZmERS1a and ZmERS1b, and ZmETR2, encoded by ZmETR2a and ZmETR2b. In this study, we introduced a Cys to Tyr mutation in the transmembrane domain of ZmERS1b and ZmETR2b that is present in the etr1-1 dominant negative mutant and expressed each protein in Arabidopsis. Mutant Zmers1b and Zmetr2b receptors conferred ethylene insensitivity and Arabidopsis expressing Zmers1b or Zmetr2b were larger and exhibited a delay in leaf senescence characteristic of ethylene insensitive Arabidopsis mutants. Zmers1b and Zmetr2b were dominant and functioned equally well in a hemizygous or homozygous state. Expression of the Zmers1b N-terminal transmembrane domain was sufficient to exert dominance over endogenous Arabidopsis ethylene receptors whereas the Zmetr2b N-terminal domain failed to do so. Neither Zmers1b nor Zmetr2b functioned in the absence of subfamily 1 ethylene receptors, i.e., ETR1 and ERS1. These results suggest that Cys65 in maize ZmERS1b and ZmETR2b plays the same role that it does in Arabidopsis receptors. Moreover, the results demonstrate that the mutant maize ethylene receptors are functionally dependent on subfamily 1 ethylene receptors in Arabidopsis, indicating substantial functional conservation between maize and Arabidopsis ethylene receptors despite their sequence divergence.

Arabidopsis thaliana knockout lines for the plant-specific eukaryotic translation initiation factors eIFiso4G1 (i4g1) and eIFiso4G2 (i4g2) genes have been obtained. To address the potential for functional redundancy of these genes, homozygous double mutant lines were generated by crossing individual knockout lines. Both single and double mutant plants were analyzed for changes in gross morphology, development, and responses to selected environmental stressors. Single gene knockouts appear to have minimal effect on morphology, germination rate, growth rate, flowering time, or fertility. However, double mutant i4g1/i4g2 knockout plants show reduced germination rates, slow growth rates, moderate chlorosis, impaired fertility and reduced long term seed viability. Double mutant plants also exhibit altered responses to dehydration, salinity, and heat stress. The i4g2 and i4g1/i4g2 double mutant has reduced amounts of chlorophyll a and b suggesting a role in the expression of chloroplast proteins. General protein synthesis did not appear to be affected as the levels of gross protein expression did not appear to change in the mutants. The lack of a phenotype for either of the single mutants suggests there is considerable functional overlap. However, the strong phenotypes observed for the double mutant indicates that the individual gene products may have specialized roles in the expression of proteins involved in plant growth and development.

Primary enucleation of the eye with retinoblastoma is a widely accessible, life-saving treatment for retinoblastoma. This study evaluated the survival of patients following primary enucleation based on AJCC 8th edition staging. Included were 700 consecutive patients (700 eyes) treated with primary enucleation at 29 Chinese treatment centers between 2006 and 2015. Excluded were patients with less than one year follow-up, bilateral retinoblastoma, clinical evidence of extraocular disease at diagnosis, or prior focal or systemic therapy. The 5-year overall survival was 95.5%, and 5-year disease-specific survival (DSS) was 95.7%. Survival was better when enucleation was 26 days (96.1% vs. 86.9%; p = 0.017). Patients with eyes presenting with raised intraocular pressure with neovascularization and/or buphthalmos (cT3c) had worse 5-year DSS (87.1%) than those without (cT2b, 99.1%; cT3b, 98.7%; cT3d, 97.2%) (p < 0.05). The 5-year DSS based on pathological staging was pT1 (99.5%), pT2a (95.5%), pT3a (100%), pT3b (93.0%), pT3c/d (92.3%), and pT4 (40.9%). Patients with pT3 pathology who received six cycles of adjuvant chemotherapy had better 5-year DSS (97.7%) than those with no chemotherapy (88.1%; p = 0.06) and those who underwent 1–3 cycles (86.9%, p = 0.02) or 4–5 cycles (89.3%, p = 0.06). Patients with pT4 pathology who received six cycles of chemotherapy had better 5-year DSS than those with 0–5 cycles (63.6% vs. 16.7%; p = 0.02). Prompt primary enucleation yielded high long-term survival for children with retinoblastoma. The AJCC 8th edition staging is predictive of survival.

Intraocular surgery is tabooed in retinoblastoma management, due to the concern of lethal extraocular spread. We reviewed the outcomes of consecutive children with intraocular retinoblastoma diagnosed at 29 Chinese centers between 2012–2014. We compared the outcomes of three categories of treatment: eye salvage including tylectomy (Group I), eye salvage without tylectomy (Group II), and primary enucleation (Group III). A total of 960 patients (1243 eyes) were diagnosed: 256 in Group I, 370 in Group II, and 293 in Group III; 41 patients abandoned treatment upfront. The estimated 5-year overall survivals (OS) were, for Group I, 94%, for Group II 89%, and for Group III 95%. The estimated 5-year disease-specific survivals (DSS) were, for Group I, 96%, for Group II 90%, and for Group III 95%. Patients in Group I had a significantly higher 5-year DSS than patients in Group II (p = 0.003) and not significantly different than patients in Group III (p = 0.367). Overall survival was not compromised by the inclusion of tylectomy in eye salvage therapy compared to eye salvage without tylectomy or primary enucleation. Disease-specific survival was better when tylectomy was included in eye salvage treatments. Tylectomy as part of multimodal treatment may contribute to the care of retinoblastoma patients with chemotherapy-resistant tumor, eyes with concomitant ocular complications, or at the risk of treatment abandonment.

Treatment abandonment is a leading cause of death in children with retinoblastoma worldwide. We studied children who abandoned treatment upfront at diagnosis to delineate the natural history of untreated retinoblastoma. Studied were children who received no treatment, diagnosed between 2007 and 2017 at 29 Chinese centers. Data were retrospectively collected from medical chart reviews and interviews with each patient’s family. During the study period, 44 children received no treatment after diagnosis of retinoblastoma. Clinical or radiologic evidence of orbital extension was available for 25 children, and radiologic evidence of systemic metastasis was available for 12 children. Median times from diagnosis of intraocular tumor to orbital disease was 13.7 months, orbital disease to metastasis was 2.6 months, and metastasis to death was 2.0 months. Children with brain metastasis had shorter survival than those with metastasis to other sites (median 1.0 vs. 3.1 months; p = 0.015). Overall, 36% of patients died within 12 months of diagnosis, 77% within 24 months, 95% within 36 months and 100% within 48 months. While multiple factors influence refusal of treatment, insights into the natural history of retinoblastoma derived from real-world evidence can inform clinicians and parents that retinoblastoma is life-threatening and encourage urgent treatment at diagnosis.

En prenant pour terrain le Québec et pour objet la mise au rôle du contentieux locatif, un des plus volumineux au Québec comme dans les sociétés occidentales en général, les auteurs interrogent les méthodes et les pratiques administratives mises en œuvre pour réduire les délais judiciaires. Dans la lignée des travaux qui dénoncent l'introduction d'une << rationalité managériale >> et d'une << gouvernance par les nombres >> dans les administrations judiciaires, les auteurs défendent l'hypothèse selon laquelle l'analyse statistique qui organise la lutte contre les délais judiciaires occulte les contradictions et les inégalités sociales qui structurent la société. Cette méthode comptable, qui régule le travail judiciaire et qui fixe les cibles à atteindre en termes de performance, d'efficacité et de célérité des tribunaux, en arrive ainsi à masquer les enjeux sociaux, sanitaires et politiques du temps judiciaire. Elle contribuerait alors à produire et à reproduire les inégalités sociales en matière d'accès à la justice.This article, taking Québec as its field and the scheduling of residential tenancy disputes as its focus (which are amongst the most frequent in Québec, as in most of the Western societies), questions the administrative methods and practices used to reduce judicial delay. In the wake of work that looks at the introduction of 'managerial logic' and a form of 'governance by numbers' in the field of judicial administration, this article defends the hypothesis that the statistical analysis used in the fight against judicial delay obscures the contradictions and social inequalities that structure society. The accounting approach, which regulates judicial work and set targets for performance, efficiency and swiftness in the court system, helps mask social, public health and political issues relating to the allocation of judicial time. As a result, it helps produce and reproduce social inequalities that have an impact on access to justice.En este artwulo se toma como referenda la provincia de Quebec, y se tiene por objeto el proceso contencioso de inquilinato (considerado como uno de los mâs vastos en Quebec y en las sociedades occidentales en general). En dicho artwulo se cuestionan los métodos y las prâcticas administrativas utilizadas para reducir los lapsos judiciales. De conformidad con las labores relacionadas con la introduccion de una << racionalidad de la gestion >> y de un modo de <<<< gobernanza de las cifras >> en las administraciones judiciales, este artwulo defiende la hipotesis de que el anâlisis estadistico que lidia contra los lapsos procesales oculta las contradicciones y las desigualdades sociales que estructuran la sociedad. Este método de contabilidad que regula el trabajo judicial, y que determina los objetivos que se deben alcanzar en términos de rendimiento, eficacia y celeridad por parte de los tribunales participa de esta forma para ocultar los desafios sociales, sanitarios y polüicos del plazo judicial, y participaria, asimismo, en la produccion y la reproduccion de las desigualdades sociales en los términos de acceso a la justicia., From Fighting Judicial Delay to Organizing a Two-Speed Justice System : Case Management at Québec's Rental BoardDe la lucha contra los lapsos judiciales a la organizacion de una justicia a [...]