The RPD3L deacetylation complex is required for facultative heterochromatin repression in .

Repression of facultative heterochromatin is essential for developmental processes in numerous organisms. Methylation of histone H3 lysine 27 (H3K27) by Polycomb repressive complex 2 is a prominent feature of facultative heterochromatin in both fungi and higher eukaryotes. Although this methylation is frequently associated with silencing, the detailed mechanism of repression remains incompletely understood.

Paraneoplastic hypercalcemia in a canine patient with a mandibular salivary carcinoma.

Objective: To describe a novel presentation of paraneoplastic hypercalcemia caused by a canine salivary carcinoma.

Animal: A 6-year-old intact male Husky with hypercalcemia and a spontaneous salivary carcinoma, stage III.

Clinical Presentation, Progression, And Procedures: The dog presented with polyuria, polydipsia, and hypercalcemia.

Evaluation of a multiagent chemotherapy protocol combining vincristine, cyclophosphamide, mitoxantrone and prednisolone (CMOP) for treatment of feline intermediate-large cell lymphoma.

Objectives: The aim of this study was to determine response rates, median progression-free intervals (PFIs) and median survival times (MSTs) for cats with intermediate-large cell lymphoma treated with a vincristine, cyclophosphamide, mitoxantrone and prednisolone (CMOP) protocol. A secondary objective was to determine the tolerability of mitoxantrone used within this multiagent protocol.

Methods: The medical records of 31 cats treated at a single institution between 2009 and 2022 were reviewed to identify suitable cases.

Initiation of fatty acid biosynthesis in Pseudomonas putida KT2440.

Deciphering the mechanisms of bacterial fatty acid biosynthesis is crucial for both the engineering of bacterial hosts to produce fatty acid-derived molecules and the development of new antibiotics. However, gaps in our understanding of the initiation of fatty acid biosynthesis remain. Here, we demonstrate that the industrially relevant microbe Pseudomonas putida KT2440 contains three distinct pathways to initiate fatty acid biosynthesis.

Retrospective assessment of tolerability and efficacy of zoledronate in the palliative treatment of cancer-bearing dogs.

Zoledronate is a bisphosphonate frequently used for the treatment of hypercalcaemia of malignancy and tumour-associated bone pain in dogs, however, there is a paucity of information regarding its use in veterinary medicine. The aim of this retrospective study was to report the tolerability of zoledronate in the palliative treatment of cancer-bearing dogs and secondarily to to assess the efficacy of zoledronate for the treatment of hypercalcaemia of malignancy. Thirty-seven dogs (22 with tumour-associated bone pain and 15 with hypercalcaemia of malignancy) that received 114 zoledronate infusions were included.

The ACF chromatin-remodeling complex is essential for Polycomb repression.

Establishing and maintaining appropriate gene repression is critical for the health and development of multicellular organisms. Histone H3 lysine 27 (H3K27) methylation is a chromatin modification associated with repressed facultative heterochromatin, but the mechanism of this repression remains unclear. We used a forward genetic approach to identify genes involved in transcriptional silencing of H3K27-methylated chromatin in the filamentous fungus .

Selection and Characterization of Mutants Defective in DNA Methylation in .

DNA methylation, a prototypical epigenetic modification implicated in gene silencing, occurs in many eukaryotes and plays a significant role in the etiology of diseases such as cancer. The filamentous fungus places DNA methylation at regions of constitutive heterochromatin such as in centromeres and in other A:T-rich regions of the genome, but this modification is dispensable for normal growth and development. This and other features render an excellent model to genetically dissect elements of the DNA methylation pathway.

Evolutionarily ancient BAH-PHD protein mediates Polycomb silencing.

Methylation of histone H3 lysine 27 (H3K27) is widely recognized as a transcriptionally repressive chromatin modification but the mechanism of repression remains unclear. We devised and implemented a forward genetic scheme to identify factors required for H3K27 methylation-mediated silencing in the filamentous fungus and identified a bromo-adjacent homology (BAH)-plant homeodomain (PHD)-containing protein, EPR-1 (effector of polycomb repression 1; NCU07505). EPR-1 associates with H3K27-methylated chromatin, and loss of EPR-1 de-represses H3K27-methylated genes without loss of H3K27 methylation.

Identification of a PRC2 Accessory Subunit Required for Subtelomeric H3K27 Methylation in Neurospora crassa.

Polycomb repressive complex 2 (PRC2) catalyzes methylation of histone H3 at lysine 27 (H3K27) in genomic regions of most eukaryotes and is critical for maintenance of the associated transcriptional repression. However, the mechanisms that shape the distribution of H3K27 methylation, such as recruitment of PRC2 to chromatin and/or stimulation of PRC2 activity, are unclear. Here, using a forward genetic approach in the model organism , we identified two alleles of a gene, , encoding an unknown RC2 ccessory ubunit (PAS).

Marked Strains for Competition Experiments and Bayesian Methods for Fitness Estimates.

The filamentous fungus , a model microbial eukaryote, has a life cycle with many features that make it suitable for studying experimental evolution. However, it has lacked a general tool for estimating relative fitness of different strains in competition experiments. To remedy this need, we constructed strains that contain a modified locus and developed an assay for detecting the proportion of the marked strain using a post PCR high resolution melting assay.

Preliminary assessment of serum clusterin as a potential biomarker for canine lymphoma.

Clusterin (CLU), also known as apolipoprotein J, is a widely expressed, heterodimeric, glycoprotein, important in tumourigenesis, apoptosis and immunoregulation. In humans, CLU expression has been associated with anaplastic large cell and Hodgkin's lymphoma. In this study, serum CLU levels in dogs with multicentric lymphoma (MLSA) were compared with healthy control dogs, using both western blot and enzyme-linked immunosorbent assay (ELISA).

Spinal extradural T-cell lymphoma with paraneoplastic hypereosinophilia in a dog: clinicopathological features, treatment, and outcome.

Spinal lymphoma is a rare manifestation of a common canine hematopoietic neoplasia. Description of treatment, outcome, and MRI features are scarce. The latter can be heterogeneous, stressing the importance of lesion excision and analysis.

Telomere repeats induce domains of H3K27 methylation in Neurospora.

Development in higher organisms requires selective gene silencing, directed in part by di-/trimethylation of lysine 27 on histone H3 (H3K27me2/3). Knowledge of the cues that control formation of such repressive Polycomb domains is extremely limited. We exploited natural and engineered chromosomal rearrangements in the fungus to elucidate the control of H3K27me2/3.

Loss of HP1 causes depletion of H3K27me3 from facultative heterochromatin and gain of H3K27me2 at constitutive heterochromatin.

Methylated lysine 27 on histone H3 (H3K27me) marks repressed "facultative heterochromatin," including developmentally regulated genes in plants and animals. The mechanisms responsible for localization of H3K27me are largely unknown, perhaps in part because of the complexity of epigenetic regulatory networks. We used a relatively simple model organism bearing both facultative and constitutive heterochromatin, Neurospora crassa, to explore possible interactions between elements of heterochromatin.

Progress in research on Tourette syndrome.

Tourette syndrome (TS) is a heritable neuropsychiatric disorder commonly complicated by obsessions and compulsions, but defined by frequent unwanted movements (motor tics) and vocalizations (phonic tics) that develop in childhood or adolescence. In recent years, research on TS has progressed rapidly on several fronts. Inspired by the Fifth International Scientific Symposium on Tourette Syndrome, the articles in this special issue review advances in the phenomenology, epidemiology, genetics, pathophysiology, and treatment of TS.

A practical and objective approach to scar colour assessment.

Scarring is a significant clinical problem following dermal injury. However, scars are not a single describable entity and huge phenotypic variability is evident. Quantitative, reproducible inter-observer scar assessment is essential to monitor wound healing and the effect of scar treatments.

Current controversies on the role of behavior therapy in Tourette syndrome.

Comprehensive behavioral intervention for tics (CBIT) is a safe and effective treatment for managing the tics of Tourette syndrome (TS). In contrast to most current medications used for the treatment of tics, the efficacy of CBIT has been demonstrated in 2 relatively large, multisite trials. It also shows durability of benefit over time.

Advances in understanding and treatment of Tourette syndrome.

Tourette syndrome is a hereditary, childhood-onset neurodevelopmental disorder that was first clearly described in France in 1885. This disorder is characterized by sudden, rapid, recurrent, nonrhythmic movements (motor tics) or sounds (vocal or phonic tics), often preceded by premonitory sensations or urges. Some individuals also have psychiatric comorbidities, notably attention-deficit hyperactivity disorder or obsessive-compulsive disorder.

Parkinson's disease, proteins, and prions: milestones.

Parkinson's disease (PD) is characterized by protein accumulation in the form of Lewy bodies and neurites. It is thus reasonable to consider that alterations in protein handling in the form of increased production, impaired clearance, or both might be central to the etiopathogenesis of the disease. Increasing genetic, laboratory and pathologic evidence has accumulated over the past 25 years supporting this hypothesis.

The pattern of neuronal loss and survival may reflect differential expression of proteasome activators in Parkinson's disease.

The basis of neuronal vulnerability, degeneration, and sparing in PD are unknown, but there is increasing evidence to suggest that the ubiquitin-proteasome system (UPS) plays an important role in the pathogenesis of the disorder. In this study, we employed an immunocytochemical approach to determine if the differential expression of key UPS components in various brain regions and cells might underlie the pattern of neuronal degeneration and survival seen in PD. We showed that the ubiquitin activating enzyme (E1), ubiquitin conjugating enzyme (E2), and 26/20S proteasome alpha- and beta-subunits, are abundantly expressed in the substantia nigra pars compacta (SNc) and in cultured dopaminergic neurons.

p53 mediates nontranscriptional cell death in dopaminergic cells in response to proteasome inhibition.

Proteasome dysfunction has been demonstrated in Parkinson disease (PD), and proteasome inhibitors have been shown to induce degeneration of dopaminergic neurons in vitro and in vivo. The mechanism whereby proteasome dysfunction leads to dopaminergic cell death, however, is unknown. In this study, we show that proteasome inhibition in both PC12 cells and dopaminergic neurons derived from embryonic stem cells is associated with mitochondrial membrane permeabilization, activation of caspase-3, and nuclear changes consistent with apoptosis.

Ubiquitin-proteasome system and Parkinson's disease.

Increasing genetic, pathological, and experimental evidence suggest that neurodegeneration in both familial and sporadic forms of Parkinson's disease (PD) may be related to a defect in the capacity of the ubiquitin-proteasome system (UPS) to clear unwanted proteins, resulting in protein accumulation, aggregation, and cytotoxicity. This concept is supported by in vitro and in vivo laboratory experiments which show that inhibition of UPS function can cause neurodegeneration coupled with the formation of Lewy body-like inclusions. This hypothesis could account for the presence of protein aggregates and Lewy bodies in PD, the other biochemical features seen in the disorder, and the age-related vulnerability of the substantia nigra pars compacta.