Signatures of a jet cocoon in early spectra of a supernova associated with a γ-ray burst.

Long γ-ray bursts are associated with energetic, broad-lined, stripped-envelope supernovae1,2 and as such mark the death of massive stars. The scarcity of such events nearby and the brightness of the γ-ray burst afterglow, which dominates the emission in the first few days after the burst, have so far prevented the study of the very early evolution of supernovae associated with γ-ray bursts3. In hydrogen-stripped supernovae that are not associated with γ-ray bursts, an excess of high-velocity (roughly 30,000 kilometres per second) material has been interpreted as a signature of a choked jet, which did not emerge from the progenitor star and instead deposited all of its energy in a thermal cocoon4. Here we report multi-epoch spectroscopic observations of the supernova SN 2017iuk, which is associated with the γ-ray burst GRB 171205A. Our spectra display features at extremely high expansion velocities (around 115,000 kilometres per second) within the first day after the burst5,6. Using spectral synthesis models developed for SN 2017iuk, we show that these features are characterized by chemical abundances that differ from those observed in the ejecta of SN 2017iuk at later times. We further show that the high-velocity features originate from the mildly relativistic hot cocoon that is generated by an ultra-relativistic jet within the γ-ray burst expanding and decelerating into the medium that surrounds the progenitor star7,8. This cocoon rapidly becomes transparent9 and is outshone by the supernova emission, which starts to dominate the emission three days after the burst.

A kilonova as the electromagnetic counterpart to a gravitational-wave source.

Gravitational waves were discovered with the detection of binary black-hole mergers and they should also be detectable from lower-mass neutron-star mergers. These are predicted to eject material rich in heavy radioactive isotopes that can power an electromagnetic signal. This signal is luminous at optical and infrared wavelengths and is called a kilonova. The gravitational-wave source GW170817 arose from a binary neutron-star merger in the nearby Universe with a relatively well confined sky position and distance estimate. Here we report observations and physical modelling of a rapidly fading electromagnetic transient in the galaxy NGC 4993, which is spatially coincident with GW170817 and with a weak, short γ-ray burst. The transient has physical parameters that broadly match the theoretical predictions of blue kilonovae from neutron-star mergers. The emitted electromagnetic radiation can be explained with an ejected mass of 0.04 ± 0.01 solar masses, with an opacity of less than 0.5 square centimetres per gram, at a velocity of 0.2 ± 0.1 times light speed. The power source is constrained to have a power-law slope of -1.2 ± 0.3, consistent with radioactive powering from r-process nuclides. (The r-process is a series of neutron capture reactions that synthesise many of the elements heavier than iron.) We identify line features in the spectra that are consistent with light r-process elements (atomic masses of 90-140). As it fades, the transient rapidly becomes red, and a higher-opacity, lanthanide-rich ejecta component may contribute to the emission. This indicates that neutron-star mergers produce gravitational waves and radioactively powered kilonovae, and are a nucleosynthetic source of the r-process elements.

The unusual gamma-ray burst GRB 101225A explained as a minor body falling onto a neutron star.

The tidal disruption of a solar-mass star around a supermassive black hole has been extensively studied analytically and numerically. In these events, the star develops into an elongated banana-shaped structure. After completing an eccentric orbit, the bound debris falls into the black hole, forming an accretion disk and emitting radiation. The same process may occur on planetary scales if a minor body passes too close to its star. In the Solar System, comets fall directly into our Sun or onto planets. If the star is a compact object, the minor body can become tidally disrupted. Indeed, one of the first mechanisms invoked to produce strong gamma-ray emission involved accretion of comets onto neutron stars in our Galaxy. Here we report that the peculiarities of the 'Christmas' gamma-ray burst (GRB 101225A) can be explained by a tidal disruption event of a minor body around an isolated Galactic neutron star. This would indicate either that minor bodies can be captured by compact stellar remnants more frequently than occurs in the Solar System or that minor-body formation is relatively easy around millisecond radio pulsars. A peculiar supernova associated with a gamma-ray burst provides an alternative explanation.

Ultramicronized palmitoylethanolamide counteracts the effects of compound 48/80 in a canine skin organ culture model.

BACKGROUND: Ultramicronized palmitoylethanolamide (PEA-um) has been reported to reduce pruritus and skin lesions in dogs with moderate atopic dermatitis and pruritus. HYPOTHESIS/OBJECTIVES: A canine ex vivo skin model was used to investigate the ability of PEA-um to counteract changes induced by compound 48/80, a well-known secretagogue that causes mast cell degranulation. ANIMALS: Normal skin was obtained from three donor dogs subjected to surgery for reasons unrelated to the study. METHODS: Cultured skin biopsy samples in triplicate were treated with 10 and 100 µg/mL compound 48/80, without or with 30 µM PEA-um. Mast cell (MC) degranulation, histamine release into the culture medium, local microvascular dilatation, epidermal thickness, keratinocyte proliferation and epidermal differentiation markers were evaluated. RESULTS: Exposure of the skin organ culture to PEA-um 24 h before and 72 h concomitantly to compound 48/80 resulted in a significant decrease of degranulating MCs. PEA-um also reduced the histamine content in the culture medium by half, although the effect did not reach statistical significance. PEA-um significantly counteracted vasodilation induced by 100 µg/mL compound 48/80. Finally, PEA-um alone did not induce changes in epidermal thickness, differentiation markers, keratinocyte proliferation, MC density and/or degranulation. CONCLUSIONS AND CLINICAL IMPORTANCE: Collectively, these results support the protective action PEA-um on the skin of dogs undergoing allergic changes.

Efficacy of ultra-micronized palmitoylethanolamide in canine atopic dermatitis: an open-label multi-centre study.

BACKGROUND: Palmitoylethanolamide is a naturally occurring bioactive lipid, produced on-demand by damage-exposed cells. Palmitoylethanolamide is documented to counteract inflammation, itch and pain. OBJECTIVE: The aim of this 8-week study was to evaluate the efficacy of oral ultra-micronized palmitoylethanolamide (PEA-um) in dogs with moderate atopic dermatitis. ANIMALS: Clinicians from 39 veterinary clinics enrolled 160 dogs with nonseasonal atopic dermatitis and moderate pruritus. METHODS: This was a multi-centre open-label study. On days 0 (D0) and 56 (D56), owners evaluated pruritus with a Visual Analog Scale (VAS) and completed a validated Quality of Life (QoL) questionnaire. Veterinarians assessed the severity of skin lesions using the Canine Atopic Dermatitis Lesion Index (CADLI). RESULTS: Mean pruritus VAS score decreased from 5.7 ± 0.08 cm (range 3.8-7.9 cm) to 3.63 ± 0.19 cm (range 0.1-9.2 cm) (P < 0.0001). At D56, 58% of dogs showed a greater than 2 cm reduction from baseline and 30% showed an absent-to-very mild pruritus (VAS ≤ 2 cm). Mean total CADLI at D56 decreased significantly (P < 0.0001); in 62% of dogs this score reached a value in the remission range (≤5). Mean total QoL score was significantly decreased (P < 0.0001) with 45% of dogs reaching QoL values described for healthy animals. Tolerability was good-to-excellent with only four dogs reporting treatment associated reversible adverse events. CONCLUSIONS AND CLINICAL IMPORTANCE: PEA-um appears to be effective and safe in reducing pruritus and skin lesions, and in improving QoL in dogs with moderate atopic dermatitis and moderate pruritus.

A very faint core-collapse supernova in M85.

An anomalous transient in the early Hubble-type (S0) galaxy Messier 85 (M85) in the Virgo cluster was discovered by Kulkarni et al. on 7 January 2006 that had very low luminosity (peak absolute R-band magnitude M(R) of about -12) that was constant over more than 80 days, red colour and narrow spectral lines, which seem inconsistent with those observed in any known class of transient events. Kulkarni et al. suggest an exotic stellar merger as the possible origin. An alternative explanation is that the transient in M85 was a type II-plateau supernova of extremely low luminosity, exploding in a lenticular galaxy with residual star-forming activity. This intriguing transient might be the faintest supernova that has ever been discovered.

An enigmatic long-lasting gamma-ray burst not accompanied by a bright supernova.

Gamma-ray bursts (GRBs) are short, intense flashes of soft gamma-rays coming from the distant Universe. Long-duration GRBs (those lasting more than approximately 2 s) are believed to originate from the deaths of massive stars, mainly on the basis of a handful of solid associations between GRBs and supernovae. GRB 060614, one of the closest GRBs discovered, consisted of a 5-s hard spike followed by softer, brighter emission that lasted for approximately 100 s (refs 8, 9). Here we report deep optical observations of GRB 060614 showing no emerging supernova with absolute visual magnitude brighter than M(V) = -13.7. Any supernova associated with GRB 060614 was therefore at least 100 times fainter, at optical wavelengths, than the other supernovae associated with GRBs. This demonstrates that some long-lasting GRBs can either be associated with a very faint supernova or produced by different phenomena.

The association of GRB 060218 with a supernova and the evolution of the shock wave.

Although the link between long gamma-ray bursts (GRBs) and supernovae has been established, hitherto there have been no observations of the beginning of a supernova explosion and its intimate link to a GRB. In particular, we do not know how the jet that defines a gamma-ray burst emerges from the star's surface, nor how a GRB progenitor explodes. Here we report observations of the relatively nearby GRB 060218 (ref. 5) and its connection to supernova SN 2006aj (ref. 6). In addition to the classical non-thermal emission, GRB 060218 shows a thermal component in its X-ray spectrum, which cools and shifts into the optical/ultraviolet band as time passes. We interpret these features as arising from the break-out of a shock wave driven by a mildly relativistic shell into the dense wind surrounding the progenitor. We have caught a supernova in the act of exploding, directly observing the shock break-out, which indicates that the GRB progenitor was a Wolf-Rayet star.

Polystyrene nanoplastics affect the human ubiquitin structure and ubiquitination in cells: a high-resolution study.

Humans are estimated to consume several grams per week of nanoplastics (NPs) through exposure to a variety of contamination sources. Nonetheless, the effects of these polymeric particles on living systems are still mostly unknown. Here, by means of CD, NMR and TEM analyses, we describe at an atomic resolution the interaction of ubiquitin with polystyrene NPs (PS-NPs), showing how a hard protein corona is formed. Moreover, we report that in human HeLa cells exposure to PS-NPs leads to a sensible reduction of ubiquitination. Our study overall indicates that PS-NPs cause significant structural effects on ubiquitin, thereby influencing one of the key metabolic processes at the base of cell viability.

Calcium sulfate stimulates pulp stem cells towards osteoblasts differentiation.

Calcium sulfate (CaS) is a highly biocompatible material and enhances bone formation in vivo. However, how CaS alters osteoblast activity to promote bone formation is poorly understood. To study how CaS can induce osteoblast differentiation in mesenchymal stem cells, the expression levels of bone related genes and mesenchymal stem cells marker were compared in normal osteoblasts and dental pulp stem cells, using real time Reverse Transcription-Polymerase Chain Reaction. Gene differentially expressed between the two cells type were the trascriptional factor RUNX2, osteopontin (SPP1), COL1A1 (collagen type 1α1) and alkaline phosphatase (ALPL). The obtained results demonstrated that CaS strongly influences the behavior of DPSCs in vitro enhancing proliferation, differentiation and deposition of matrix.

Adelmidrol increases the endogenous concentrations of palmitoylethanolamide in canine keratinocytes and down-regulates an inflammatory reaction in an in vitro model of contact allergic dermatitis.

This study aimed to investigate potential new target(s)/mechanism(s) for the palmitoylethanolamide (PEA) analogue, adelmidrol, and its role in an in vitro model of contact allergic dermatitis. Freshly isolated canine keratinocytes, human keratinocyte (HaCaT) cells and human embryonic kidney (HEK)-293 cells, wild-type or transfected with cDNA encoding for N-acylethanolamine-hydrolysing acid amidase (NAAA), were treated with adelmidrol or azelaic acid, and the concentrations of endocannabinoids (anandamide and 2-arachidonoylglycerol) and related mediators (PEA and oleoylethanolamide) were measured. The mRNA expression of PEA catabolic enzymes (NAAA and fatty acid amide hydrolase, FAAH), and biosynthetic enzymes (N-acyl phosphatidylethanolamine-specific phospholipase D, NAPE-PLD) and glycerophosphodiester phosphodiesterase 1, was also measured. Brain or HEK-293 cell membrane fractions were used to assess the ability of adelmidrol to inhibit FAAH and NAAA activity, respectively. HaCaT cells were stimulated with polyinosinic-polycytidylic acid and the release of the pro-inflammatory chemokine, monocyte chemotactic protein-2 (MCP-2), was measured in the presence of adelmidrol. Adelmidrol increased PEA concentrations in canine keratinocytes and in the other cellular systems studied. It did not inhibit the activity of PEA catabolic enzymes, although it reduced their mRNA expression in some cell types. Adelmidrol modulated the expression of PEA biosynthetic enzyme, NAPE-PLD, in HaCaT cells, and inhibited the release of the pro-inflammatory chemokine MCP-2 from stimulated HaCaT cells. This study demonstrates for the first time an 'entourage effect' of adelmidrol on PEA concentrations in keratinocytes and suggests that this effect might mediate, at least in part, the anti-inflammatory effects of this compound in veterinary practice.

Andes virus associated with hantavirus pulmonary syndrome in northern Argentina and determination of the precise site of infection.

Hantavirus pulmonary syndrome (HPS) has been documented in the Salta and Jujuy provinces of northern Argentina since 1991 and 1997, respectively, accounting for almost 50% of the cases of HPS reported in this country. Andes (AND) virus, specifically the AND virus Nort lineage, was previously associated with human disease in this region. Genetic analysis of viral medium RNA segments obtained from 18 HPS cases showed the existence of three AND virus Nort sublineages co-circulating in these two provinces. They showed a nucleotide sequence diversity of up to 11.1% between the sublineages. The putative site of infection of one of these cases (Sal3/97) was determined. A 100% nucleotide sequence identity was observed between the viral sequence found in patient Sal3/97 and in two virus-positive Oligoryzomys chacoensis captured in the same place where the case lived and worked. These results indicated the putative site of infection and identified this rodent species as the source of infection.

[Changes in the levels of delta-aminolevulinic acid dehydratase in chronic alcoholic patients]. / Modificaciones de los niveles de ácido delta aminolevúlico dehidrasa en pacientes alcohólicos crónicos.

Medical and biochemical analysis were performed on 58 patients with chronic alcoholism. In accordance with medical characterisation, patients were divided in three groups: A (patients having only hepatopathy), B (patients with hepatopathy and neuropathy) and C (patients having only alcoholic neuropathy). Simultaneously, several parameters related to heme biosynthesis were examined. Urinary delta-aminolevulic acid (ALA), porphobilinogen (PBG) and porphyrins and fecal porphyrins measurements did not show significant difference among all studied groups. The activities of ALA-dehydratase (ALA-D), uroporphyrinogen-I-synthase (URO-I-S) and uroporphyrinogen-III-synthase (URO-III-S) were monitored in peripheral erythrocytes. From the enzymes measured, only ALA-D levels in groups B and C were significantly depressed (p < 0.002) compared with normal subjects. The decrease in ALA-D correlated with the degree of neuropathy.

[Cryptogenetic ulcerative colitis. Our clinical experience with new therapeutic approaches]. / Colite ulcerosa criptogenetica. Nostra esperienza clinica sulle nuove vedute terapeutiche.

Sixteen patients with flare-ups of ulcerative colitis were studied. Before and after treatment, patients were submitted to the customary laboratory tests and to x-ray (contrast enema) and endoscopic examination, biopsy material being harvested during the latter. Treatment consisted in the oral administration of 2-4 g 5-ASA daily for 30 days. Only one patient did not tolerate 5-ASA which was withdrawn. All other patients had good or very good results with remission of symptoms.

[Simvastatin in the treatment of hypercholesterolemia]. / La simvastatina nel trattamento delle ipercolesterolemie.

We have treated twelve patients with simvastatin: six had type IIA hypercholesterolaemia and the other six had type IIB. These patients have been examined before and after therapy, by an ophthalmologist. After therapy, the levels of the total cholesterol and triglycerides were decreased while HDL cholesterol was increased. Untoward side effects of ophthalmologic alterations were not observed.

[Hyperlipidemia: physiopathology and our experience in the ambulatory care of 3 groups of patients undergoing blood lipid normalization treatment]. / Le iperlipidemie. Fisiopatologia e nostre esperienze ambulatoriali su tre gruppi di pazienti sottoposti a trattamento normolipemizzante.

The authors tested the efficacy of three different lipid-lowering drugs in subjects with more or less severe alterations of the lipoprotein pattern. All subjects were submitted to blood tests prior to and at the end of treatment with special attention to the trend of the lipid pattern, assaying cholesterol, HDL, LDL, triglyceride, total lipid blood levels and lipid electrophoresis. The drugs employed were: pantothenic acid, sulodexide, and DEAE-dextran.

Effects of palmitoylethanolamide on immunologically induced histamine, PGD2 and TNFalpha release from canine skin mast cells.

Palmitoylethanolamide (PEA) is an endocannabinoid-like compound and the parent molecule of the aliamide family, a group of fatty acid amides able to act through the down-regulation of mast cell degranulation. PEA has been proven to exert both analgesic and anti-inflammatory activity, and recent studies have shown its ability in reducing clinical symptoms of inflammatory skin diseases, both in humans and in animals. Although its pharmacological efficacy is well known, the mechanism of action of this family of compounds is still unclear. To better understand the cellular effects of aliamides in dogs, canine mast cells freshly isolated from skin biopsies were incubated with IgE-rich serum and were challenged with anti-canine IgE. Histamine, prostaglandin D(2) (PGD(2)) and tumour necrosis factor-alpha (TNFalpha) release was measured in the presence and absence of increasing concentrations of PEA, ranging from 10(-8)M to 10(-5)M. Histamine, PGD(2) and TNFalpha release, immunologically induced by canine anti-IgE, were significantly inhibited in the presence of PEA. The maximum inhibitory effect on histamine release was observed at 3x10(-6)M PEA concentration achieving an inhibition of 54.3+/-5.2%. PGD(2) release was significantly inhibited at 10(-5)M and 10(-6)M PEA concentrations with 25.5+/-10.2% and 14.6+/-5.6% of inhibition, respectively. Finally, PEA inhibited TNFalpha release to 29.2+/-2.0% and 22.1+/-7.2%, at concentrations of 10(-5)M and 3x10(-6)M, respectively. The results obtained in the present study showed the ability of the aliamide PEA to down-modulate skin mast cell activation. Therefore, our findings suggest that the beneficial effect of PEA, observed in inflammation and pain clinical studies, could be due, at least in part, to its ability to inhibit the release of both preformed and newly synthesised mast cell mediators.

Genetic diversity, distribution, and serological features of hantavirus infection in five countries in South America.

Since 1995 when the first case of hantavirus pulmonary syndrome (HPS) was reported in Patagonia, there have been more than 400 cases of HPS reported in five countries in South America. The first case of HPS was associated with Andes (AND) virus. In this study, we report on the genetic diversity, geographical distribution, and serological features of hantavirus infection in six countries in South America based on 87 HPS cases from Argentina, Bolivia, Chile, Paraguay, and Uruguay. An early immunoglobulin M (IgM), IgA, and IgG humoral response was observed in almost all HPS cases. The IgM response appears to peak 1 or 2 days after the onset of symptoms. Peak IgG antibody titers occur mostly after the first week. Low IgG titers or the absence of IgG was associated with higher mortality rates. The IgA response peaks around day 15 and then rapidly decreases. The results of phylogenetic analysis based on partial M-fragment G1- and G2-encoding sequences showed that HPS cases from the five countries were infected with viruses related to AND or Laguna Negra (LN) virus. Within AND virus-infected persons, at least five major genetic lineages were found; one lineage was detected in Uruguayan and Argentinean cases from both sides of the Rio de la Plata river. Two Paraguayan patients were infected with a virus different from LN virus. According to the results of phylogenetic analyses, this virus probably belongs to a distinct lineage related more closely to the AND virus than to the LN virus, suggesting that there is probably an Oligoryzomys-borne viral variant circulating in Paraguay. These studies may contribute to a better understanding of hantavirus human infection in South America.