Congenital infiltrative lipomas and retroperitoneal perirenal lipomas in a calf

BACKGROUND: Congenital lipocytic tumours have rarely been reported in cattle. Lipomas are benign tumours, but infiltrative lipomas have significant health implications due to their aggressive infiltrative growth pattern. CASE PRESENTATION: A calf was born with skeletal malformations and soft tissue proliferations, primarily on the external thoracic wall. The calf was euthanized for welfare reasons and submitted for post mortem examination. Necropsy, histopathology and post mortem computed tomography scanning revealed two types of lipocytic tumours. Widespread infiltrative lipomas were present in the muscles and connective tissues along the vertebral column and diffusely invaded the external soft tissues of the right thoracic wall. The neoplastic lipocytes had invaded intervertebral spaces thus causing congenital vertebral malformations, and further invaded the vertebral canal and the bone marrow of coccygeal vertebrae. Periosteal localization of the tumour was associated with costal hyperostosis. Two large retroperitoneal lipomas enclosed the kidneys and occupied much of the abdominal space. CONCLUSION: The development of congenital bone malformation in this calf illustrates the severe consequences of the infiltrative and aggressive growth of infiltrative lipomas during foetal development. The congenital retroperitoneal lipomas occupied a large part of abdominal cavity, but did not invade the adjacent tissues. Due to their large size, perirenal lipomas should be considered in calves with distended abdomen, even in cases without other signs of tumours

A Submillimetre Survey of the Hubble Deep Field: Unveiling Dust-Enshrouded Star Formation in the Early Universe

The advent of sensitive sub-mm array cameras now allows a proper census of dust-enshrouded massive star-formation in very distant galaxies, previously hidden activity to which even the deepest optical images are insensitive. We present the deepest sub-mm survey, taken with the SCUBA camera on the James Clerk Maxwell Telescope (JCMT) and centred on the Hubble Deep Field (HDF). The high source density on this image implies that the survey is confusion-limited below a flux density of 2 mJy. However within the central 80 arcsec radius independent analyses yield 5 reproducible sources with S(850um) > 2 mJy which simulations indicate can be ascribed to individual galaxies. These data lead to integral source counts which are completely inconsistent with a no evolution model, whilst the combined brightness of the 5 most secure sources in our map is sufficient to account for 30-50% of the previously unresolved sub-mm background, and statistically the entire background is resolved at about the 0.3 mJy level. Four of the five brightest sources appear to be associated with galaxies which lie in the redshift range 2 < z < 4. With the caveat that this is a small sample of sources detected in a small survey area, these submm data imply a star-formation density over this redshift range that is at least five times higher than that inferred from the rest-frame ultraviolet output of HDF galaxies.Comment: to appear in the proceedings of `The Birth of Galaxies', Xth Rencontres de Blois, 4 pages, 1 postscript figure, uses blois.sty (included

Array Comparative Genomic Hybridization Analysis Reveals Significantly Enriched Pathways in Canine Oral Melanoma

Human Mucosal Melanoma (hMM) is an aggressive neoplasm of neuroectodermal origin with distinctive features from the more common cutaneous form of malignant melanoma (cMM). At the molecular level, hMMs are characterized by large chromosomal aberrations rather than single-nucleotide mutations, typically observed in cMM. Given the scarcity of available cases, there have been many attempts to establish a reliable animal model. In pet dogs, Canine Oral Melanoma (COM) is the most common malignant tumor of the oral cavity, sharing clinical and histological aspects with hMM. To improve the knowledge about COM\u2019s genomic DNA alterations, in the present work, formalin-fixed, paraffin-embedded (FFPE) samples of COM from different European archives were collected to set up an array Comparative Genomic Hybridization (aCGH) analysis to estimate recurrent Copy Number Aberrations (CNAs). DNA was extracted in parallel from tumor and healthy fractions and 19 specimens were successfully submitted to labeling and competitive hybridization. Data were statistically analyzed through GISTIC2.0 and a pathway-enrichment analysis was performed with ClueGO. Recurrent gained regions were detected, affecting chromosomes CFA 10, 13 and 30, while lost regions involved chromosomes CFA 10, 11, 22, and 30. In particular, CFA 13 showed a whole-chromosome gain in 37% of the samples, while CFA 22 showed a whole-chromosome loss in 25%. A distinctive sigmoidal trend was observed in CFA 10 and 30 in 25 and 30% of the samples, respectively. Comparative analysis revealed that COM and hMM share common chromosomal changes in 32 regions. MAPK- and PI3K-related genes were the most frequently involved, while pathway analysis revealed statistically significant perturbation of cancer-related biological processes such as immune response, drug metabolism, melanocytes homeostasis, and neo-angiogenesis. The latter is a new evidence of a significant involvement of neovascularization-related pathways in COMs and can provide the rationale for future application in anti-cancer targeted therapies

The FIRST Bright Quasar Survey. II. 60 Nights and 1200 Spectra Later

We have used the VLA FIRST survey and the APM catalog of the POSS-I plates as the basis for constructing a new radio-selected sample of optically bright quasars. This is the first radio-selected sample that is competitive in size with current optically selected quasar surveys. Using only two basic criteria, radio-optical positional coincidence and optical morphology, quasars and BL Lacs can be identified with 60% selection efficiency; the efficiency increases to 70% for objects fainter than magnitude 17. We show that a more sophisticated selection scheme can predict with better than 85% reliability which candidates will turn out to be quasars. This paper presents the second installment of the FIRST Bright Quasar Survey with a catalog of 636 quasars distributed over 2682 square degrees. The quasar sample is characterized and all spectra are displayed. The FBQS detects both radio-loud and radio-quiet quasars out to a redshift z>3. We find a large population of objects of intermediate radio-loudness; there is no evidence in our sample for a bimodal distribution of radio characteristics. The sample includes ~29 broad absorption line quasars, both high and low ionization, and a number of new objects with remarkable optical spectra.Comment: 41 pages plus 39 gifs which contain all quasar spectra. Accepted for publication in the Astrophysical Journal Supplement Serie

Sensitive observations at 1.4 and 250 GHz of z > 5 QSOs

We present 1.4 and 5 GHz observations taken with the Very Large Array (VLA), and observations at 250 GHz obtained with the Max-Planck millimeter bolometer (MAMBO) at the IRAM 30~m telescope, of ten optically selected Quasi-stellar Objects (QSOs) at 5.0 < z < 6.28. Four sources are detected at 1.4 GHz two of which are radio loud and are also detected at 5 GHz. These results are roughly consistent with there being no evolution of the radio-loud QSO fraction out to z~6. Three sources have been detected at 250 GHz or 350 GHz at much higher levels than their 1.4 GHz flux densities suggesting that the observed mm emission is likely thermal emission from warm dust, although more exotic possibilities cannot be precluded. The highest redshift source in our sample (J1030+0524 at z=6.28) is not detected at 1.4 or 250 GHz, but four fairly bright radio sources (flux density at 1.4GHz > 0.2 mJy) are detected in a 2' field centered on the QSO, including an edge-brightened ('FRII') double radio source with an extent of about 1'. A similar over-density of radio sources is seen in the field of the highest redshift QSO J1148+5251. We speculate that these over-densities of radio sources may indicate clusters along the lines-of-sight, in which case gravitational lensing by the cluster could magnify the QSO emission by a factor 2 or so without giving rise to arcsecond-scale distortions in the optical images of the QSOs.Comment: 25 pages, 12 figures. accepted by A

XY models with disorder and symmetry-breaking fields in two dimensions

The combined effect of disorder and symmetry-breaking fields on the two-dimensional XY model is examined. The study includes disorder in the interaction among spins in the form of random phase shifts as well as disorder in the local orientation of the field. The phase diagrams are determined and the properties of the various phases and phase transitions are calculated. We use a renormalization group approach in the Coulomb gas representation of the model. Our results differ from those obtained for special cases in previous works. In particular, we find a changed topology of the phase diagram that is composed of phases with long-range order, quasi-long-range order, and short-range order. The discrepancies can be ascribed to a breakdown of the fugacity expansion in the Coulomb gas representation. Implications for physical systems such as planar Josephson junctions and the faceting of crystal surfaces are discussed.Comment: 17 pages Latex with 5 eps figures, change: acknowledgment extende

Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract

The cytokine interleukin (IL) 25 has been implicated in the initiation of type 2 immunity by driving the expression of type 2 cytokines such as IL-5 and IL-13, although its role in the regulation of immunity and infection-induced inflammation is unknown. Here, we identify a dual function for IL-25: first, in promoting type 2 cytokine-dependent immunity to gastrointestinal helminth infection and, second, in limiting proinflammatory cytokine production and chronic intestinal inflammation. Treatment of genetically susceptible mice with exogenous IL-25 promoted type 2 cytokine responses and immunity to Trichuris. IL-25 was constitutively expressed by CD4(+) and CD8(+) T cells in the gut of mouse strains that are resistant to Trichuris, and IL-25–deficient mice on a genetically resistant background failed to develop a type 2 immune response or eradicate infection. Furthermore, chronically infected IL-25(−/−) mice developed severe infection-induced intestinal inflammation associated with heightened expression of interferon-γ and IL-17, identifying a role for IL-25 in limiting pathologic inflammation at mucosal sites. Therefore, IL-25 is not only a critical mediator of type 2 immunity, but is also required for the regulation of inflammation in the gastrointestinal tract

Safety and efficacy of pembrolizumab in combination with acalabrutinib in advanced head and neck squamous cell carcinoma: Phase 2 proof-of-concept study

PURPOSE: Programmed cell death-1 (PD-1) receptor inhibitors have shown efficacy in head and neck squamous cell carcinoma (HNSCC), but treatment failure or secondary resistance occurs in most patients. In preclinical murine carcinoma models, inhibition of Bruton\u27s tyrosine kinase (BTK) induces myeloid cell reprogramming that subsequently bolsters CD8+ T cell responses, resulting in enhanced antitumor activity. This phase 2, multicenter, open-label, randomized study evaluated pembrolizumab (anti-PD-1 monoclonal antibody) plus acalabrutinib (BTK inhibitor) in recurrent or metastatic HNSCC. PATIENTS AND METHODS: Patients received pembrolizumab 200 mg intravenously every 3 weeks, alone or in combination with acalabrutinib 100 mg orally twice daily. Safety and overall response rate (ORR) were co-primary objectives. The secondary objectives were progression-free survival (PFS) and overall survival. RESULTS: Seventy-six patients were evaluated (pembrolizumab, n = 39; pembrolizumab + acalabrutinib, n = 37). Higher frequencies of grade 3-4 treatment-emergent adverse events (AE; 65% vs. 39%) and serious AEs (68% vs. 31%) were observed with combination therapy versus monotherapy. ORR was 18% with monotherapy versus 14% with combination therapy. Median PFS was 2.7 [95% confidence interval (CI), 1.4-6.8] months in the combination arm and 1.7 (95% CI, 1.4-4.0) months in the monotherapy arm. The study was terminated due to lack of clinical benefit with combination treatment. To assess how tumor immune contexture was affected by therapy in patients with pre- and post-treatment biopsies, spatial proteomic analyses were conducted that revealed a trend toward increased CD45+ leukocyte infiltration of tumors from baseline at day 43 with pembrolizumab (monotherapy, n = 5; combination, n = 2), which appeared to be higher in combination-treated patients; however, definitive conclusions could not be drawn due to limited sample size. CONCLUSIONS: Despite lack of clinical efficacy, immune subset analyses suggest that there are additive effects of this combination; however, the associated toxicity limits the feasibility of combination treatment with pembrolizumab and acalabrutinib in patients with recurrent or metastatic HNSCC

Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation.

The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of β-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid-like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules. Supporting a hypothetical pathway from reversible to irreversible amyloid aggregation, we found that familial ALS variants of TDP-43 convert LARKS to irreversible aggregates. Our structures suggest how TDP-43 adopts both reversible and irreversible β-sheet aggregates and the role of mutation in the possible transition of reversible to irreversible pathogenic aggregation