Isoform-selective TGF-β3 inhibition for systemic sclerosis.

Background: Transforming growth factor β (TGF-β) is implicated as a key mediator of pathological fibrosis, but its pleiotropic activity in a range of homeostatic functions presents challenges to its safe and effective therapeutic targeting. There are three isoforms of TGF-β, TGF-β1, TGF-β2, and TGF-β3, which bind to a common receptor complex composed of TGF-βR1 and TGF-βR2 to induce similar intracellular signals in vitro. We have recently shown that the cellular expression patterns and activation thresholds of TGF-β2 and TGF-β3 are distinct from those of TGF-β1 and that selective short-term TGF-β2 and TGF-β3 inhibition can attenuate fibrosis in vivo without promoting excessive inflammation.

Persistent organic pollutants and trace elements detected in New Zealand fur seals (long-nosed fur seal; Arctocephalus forsteri) from New South Wales, Australia, between 1998 and 2019.

Environmental pollution is a growing threat to wildlife health and biodiversity. The relationship between marine mammals and pollutants is, however, complex and as new chemicals are introduced to ecosystems alongside concomitant, interacting threats such as climate change and habitat degradation, the cumulative impact of these stressors to wildlife continues to expand. Understanding the health of wildlife populations requires a holistic approach to identify potential threatening processes.

Gammaretroviruses, novel viruses and pathogenic bacteria in Australian bats with neurological signs, pneumonia and skin lesions.

More than 70 bat species are found in mainland Australia. While most studies of bat viromes focus on sampling seemingly healthy individuals, little is known about the viruses and bacteria associated with diseased bats. We performed traditional diagnostic techniques and metatranscriptomic sequencing on tissue samples from 43 Australian bats, comprising three flying fox (Pteropodidae) and two microbat species experiencing a range of disease syndromes, including mass mortality, neurological signs, pneumonia and skin lesions.

LOXL4, but not LOXL2, is the critical determinant of pathological collagen cross-linking and fibrosis in the lung.

Idiopathic pulmonary fibrosis is a progressive fibrotic disease characterized by excessive deposition of (myo)fibroblast produced collagen fibrils in alveolar areas of the lung. Lysyl oxidases (LOXs) have been proposed to be the central enzymes that catalyze the cross-linking of collagen fibers. Here, we report that, while its expression is increased in fibrotic lungs, genetic ablation of LOXL2 only leads to a modest reduction of pathological collagen cross-linking but not fibrosis in the lung.

Survival of Patients With Neuroblastoma After Assignment to Reduced Therapy Because of the 12- to 18-Month Change in Age Cutoff in Children's Oncology Group Risk Stratification.

Purpose: In 2006, Children's Oncology Group (COG) reclassified subgroups of toddlers diagnosed with neuroblastoma from high-risk to intermediate-risk, when the age cutoff for high-risk assignment was raised from 365 days (12 months) to 547 days (18 months). The primary aim of this retrospective study was to determine if excellent outcome was maintained after assigned reduction of therapy.

Patients And Methods: Children <3 years old at diagnosis, enrolled on a COG biology study from 1990 to 2018, were eligible (n = 9,189).

Gastrointestinal stromal tumor (GIST) presenting as a multilocular cystic intra-abdominal mass in a dog.

Background: Gastrointestinal stromal tumor (GIST) is a malignant mesenchymal neoplasm described in humans, dogs, and cats. A hallmark of diagnosis for GISTs is positive immunohistochemical labelling with c-Kit (CD117). The differentiation of GIST from other mesenchymal neoplasms of the gastrointestinal tract is pivotal to allow for initiation of appropriate treatment.

Fatal Bronchopneumonia and Tracheitis in a Green Turtle () Caused by .

A free-ranging subadult, male green turtle () presented with radiographic evidence of pneumonia and died acutely. On necropsy, the trachea and bronchi were plugged by diphtheritic membranes, comprised of fibrin, necrotic debris, and colonies of bacilli, identified as . , typically considered an opportunistic plant pathogen, has rarely been described as causing disease in animals.

Identification of an Immunogenic Medulloblastoma-Specific Fusion Involving and .

Medulloblastoma is the most common malignant brain tumor in children. Immunotherapy is yet to demonstrate dramatic results in medulloblastoma, one reason being the low rate of mutations creating new antigens in this entity. In tumors with low mutational burden, gene fusions may represent a source of tumor-specific neoantigens.

Alpha-Synuclein Pathology Coincides With Increased Number of Early Stage Neural Progenitors in the Adult Hippocampus.

Alpha-synuclein pathology driven impairment in adult neurogenesis was proposed as a potential cause of, or at least contributor to, memory impairment observed in both patients and animal models of Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). Mice overexpressing wild-type alpha-synuclein under the Thy-1 promoter (Thy1-aSyn, line 61) uniquely replicate early cognitive deficits together with multiple other characteristic motor and non-motor symptoms, alpha-synuclein pathology and dopamine loss. Here we report overt intracellular accumulation of phosphorylated alpha-synuclein in the hippocampus of these transgenic mice.

ChAdOx1 nCoV-19 (AZD1222) vaccine candidate significantly reduces SARS-CoV-2 shedding in ferrets.

Vaccines against SARS-CoV-2 are likely to be critical in the management of the ongoing pandemic. A number of candidates are in Phase III human clinical trials, including ChAdOx1 nCoV-19 (AZD1222), a replication-deficient chimpanzee adenovirus-vectored vaccine candidate. In preclinical trials, the efficacy of ChAdOx1 nCoV-19 against SARS-CoV-2 challenge was evaluated in a ferret model of infection.

Neurotensin: A novel mediator of ovulation?

The midcycle luteinizing hormone (LH) surge initiates a cascade of events within the ovarian follicle which culminates in ovulation. Only mural granulosa cells and theca cells express large numbers of LH receptors, and LH-stimulated paracrine mediators communicate the ovulatory signal within the follicle. Recent reports identified the neuropeptide neurotensin (NTS) as a product of granulosa cells.

Squamous Cell Carcinoma in Two Wild Bell's Turtles (Myuchelys bellii).

Squamous cell carcinomas in Testudines are rarely reported. Most cases in the literature describe these tumors in captive animals. We report spontaneously arising squamous cell carcinomas affecting the plastron of two wild Bell's turtles (Myuchelys bellii) from the Macdonald River in New South Wales, Australia.

Transferrin Receptor Is a Specific Ferroptosis Marker.

Ferroptosis is a type of regulated cell death driven by the iron-dependent accumulation of oxidized polyunsaturated fatty acid-containing phospholipids. There is no reliable way to selectively stain ferroptotic cells in tissue sections to characterize the extent of ferroptosis in animal models or patient samples. We address this gap by immunizing mice with membranes from lymphoma cells treated with the ferroptosis inducer piperazine erastin and screening ∼4,750 of the resulting monoclonal antibodies generated for their ability to selectively detect cells undergoing ferroptosis.

Thrombospondin 1 (THBS1) Promotes Follicular Angiogenesis, Luteinization, and Ovulation in Primates.

Angiogenesis is essential to both ovulation and the formation of the corpus luteum. The thrombospondin (THBS) family of glycoproteins plays diverse roles in regulation of angiogenesis, but the role of these vascular regulators in ovulation and luteinization remain to be elucidated. Using the cynomolgus macaque as a model for human ovulation, we demonstrated that levels of THBS1 mRNA and protein in preovulatory follicle granulosa cells increased after the ovulatory gonadotropin surge, with peak levels just before the expected time of ovulation.

Ceritinib-Induced Regression of an Insulin-Like Growth Factor-Driven Neuroepithelial Brain Tumor.

The insulin-like growth factor (IGF) pathway plays an important role in several brain tumor entities. However, the lack of inhibitors crossing the blood-brain barrier remains a significant obstacle for clinical translation. Here, we targeted the IGF pathway using ceritinib, an off-target inhibitor of the IGF1 receptor (IGF1R) and insulin receptor (INSR), in a pediatric patient with an unclassified brain tumor and a () germline mutation.

IGF1R Is a Potential New Therapeutic Target for HGNET-BCOR Brain Tumor Patients.

(1) The high-grade neuroepithelial tumor of the central nervous system with BCOR alteration (HGNET-BCOR) is a highly malignant tumor. Preclinical models and molecular targets are urgently required for this cancer. Previous data suggest a potential role of insulin-like growth factor (IGF) signaling in HGNET-BCOR.

Neural Progenitors in the Developing Neocortex of the Northern Tree Shrew () Show a Closer Relationship to Gyrencephalic Primates Than to Lissencephalic Rodents.

The neocortex is the most complex part of the mammalian brain and as such it has undergone tremendous expansion during evolution, especially in primates. The majority of neocortical neurons originate from distinct neural stem and progenitor cells (NPCs) located in the ventricular and subventricular zone (SVZ). Previous studies revealed that the SVZ thickness as well as the abundance and distribution of NPCs, especially that of basal radial glia (bRG), differ markedly between the lissencephalic rodent and gyrencephalic primate neocortex.

Personalized therapy: CNS HGNET-BCOR responsiveness to arsenic trioxide combined with radiotherapy.

High-grade neuroepithelial tumor of the central nervous system with BCOR alteration (HGNET-BCOR) is a rare, highly malignant tumor. At the time of this publication, no standard protocol exists to treat this tumor entity. In this work, we tested the responsiveness of the primary culture PhKh1 derived from tumor tissue from a pediatric HGNET-BCOR patient (P1) to inhibitors of the Sonic hedgehog pathway combined with radiation.

Placental Growth Factor Is Required for Ovulation, Luteinization, and Angiogenesis in Primate Ovulatory Follicles.

Placental growth factor (PGF) is member of the vascular endothelial growth factor (VEGF) family of angiogenesis regulators. VEGFA is an established regulator of ovulation and formation of the corpus luteum. To determine whether PGF also mediates aspects of ovulation and luteinization, macaques received gonadotropins to stimulate multiple follicular development.

Pathogenesis and molecular biology of a transmissible tumor in the Tasmanian devil.

The emergence of a fatal transmissible cancer known as devil facial tumor disease (DFTD) is threatening the iconic Tasmanian devil with extinction in the wild within the next few decades. Since the first report of the disease in 1996, DFTD has spread to over 85% of the devils' distribution and dramatically reduced devil numbers. Research into DFTD has focused on gaining a deeper understanding of the disease on multiple levels, including an accurate assessment of the tissue origin of the tumor, elucidation of how the tumor evades immune detection, and determination of how the tumor is transmitted between individuals and how it is evolving as it spreads through the population.

Adverse interaction between colchicine and ketoconazole in a Chinese shar pei.

A Chinese shar pei with a 2 yr history of episodic fever, lethargy, and shifting lameness was presumptively diagnosed with familial shar pei fever but had never been treated for the syndrome. After being presented for a superficial pyoderma with possible dermatophyte coinfection, treatment with a cephalosporin and ketoconazole were prescribed. One wk later, colchicine was initiated for familial shar pei fever using cautious dose escalation.

Cerebrospinal fluid eosinophilia is a sensitive and specific test for the diagnosis of Parelaphostrongylus tenuis in camelids in the northeastern United States.

Aberrant migration of Parelaphostrongylus tenuis in camelids results in neurologic deficits, recumbency, and sometimes death. An antemortem diagnosis of P. tenuis in camelids is typically based upon the presence of characteristic asymmetric neurologic deficits, known exposure to white-tailed deer, cerebrospinal fluid (CSF) eosinophilia, and response to treatment.