661 research outputs found
Simple Synthesis of Pyrazole-derived Dithioethers
A number of pyrazole-derived dithioethers were prepared by the reaction of diisothiuronium salts and 2-(3,5-dimethylpyrazol-1-yl)ethanol tosylate in a basic aqueous solution. Diisothiuronium salts were prepared by the reaction of thiourea with alpha,omega-dibromoalkanes containing from two to nine methylene groups. The use of these salts allowed in situ generation ions dithiolate, thus eliminating the need to use hazardous dimercaptans
Altered brain responses to specific negative emotions in schizophrenia
Esquizofrènia; Estímuls escènics; fMRIEsquizofrenia; Estímulos escénicos; fMRISchizophrenia; Scenic stimuli; fMRIDeficits in emotion processing are a core feature of schizophrenia, but their neurobiological bases are poorly understood. Previous research, mainly focused on emotional face processing and emotion recognition deficits, has shown controverted results. Furthermore, the use of faces has been questioned for not entailing an appropriate stimulus to study emotional processing. This highlights the importance of investigating emotional processing abnormalities using evocative stimuli. For the first time, we have studied the brain responses to scenic stimuli in patients with schizophrenia. We selected scenes from the IAPS that elicit fear, disgust, happiness, and sadness. Twenty-six patients with schizophrenia and thirty age-, sex- and premorbid IQ-matched healthy controls were included. Behavioral task results show that patients tended to misclassify disgust and sadness as fear. Brain responses in patients were different from controls in images eliciting disgust and fear. In response to disgust images, patients hyperactivated the right temporal cortex, which was not activated by the controls. With fear images, hyperactivation was observed in brain regions involved in fear processing, including midline regions from the medial frontal cortex to the anterior cingulate cortex, the superior frontal gyrus, inferior and superior temporal cortex, and visual areas. These results suggest that schizophrenia is characterized by hyper-responsivity to stimuli evoking high-arousal, negative emotions, and a bias towards fear in emotion recognition
Hyperspectral imaging benchmark based on machine learning for intraoperative brain tumour detection
publishedVersio
Identification of Two Protein-Signaling States Delineating Transcriptionally Heterogeneous Human Medulloblastoma
Summary: The brain cancer medulloblastoma consists of different transcriptional subgroups. To characterize medulloblastoma at the phosphoprotein-signaling level, we performed high-throughput peptide phosphorylation profiling on a large cohort of SHH (Sonic Hedgehog), group 3, and group 4 medulloblastomas. We identified two major protein-signaling profiles. One profile was associated with rapid death post-recurrence and resembled MYC-like signaling for which MYC lesions are sufficient but not necessary. The second profile showed enrichment for DNA damage, as well as apoptotic and neuronal signaling. Integrative analysis demonstrated that heterogeneous transcriptional input converges on these protein-signaling profiles: all SHH and a subset of group 3 patients exhibited the MYC-like protein-signaling profile; the majority of the other group 3 subset and group 4 patients displayed the DNA damage/apoptotic/neuronal signaling profile. Functional analysis of enriched pathways highlighted cell-cycle progression and protein synthesis as therapeutic targets for MYC-like medulloblastoma. : Using peptide phosphorylation profiling, Zomerman et al. identify two medulloblastoma phosphoprotein-signaling profiles that have prognostic value and are potentially targetable. They find that these profiles extend across transcriptome-based subgroup borders. This suggests that diverse genetic information converges on common protein-signaling pathways and highlights protein-signaling as a unique information layer. Keywords: medulloblastoma, protein-signaling, protein synthesis, MYC, TP53, proteome, phosphoproteom
Optical and infrared flares from a transient Galactic soft gamma-ray repeater
Soft gamma-ray repeaters (SGRs) are a rare type of gamma-ray transient
sources that are ocasionally detected as bursts in the high-energy sky. They
are thought to be produced by magnetars, young neutron stars with very strong
magnetic fields of the order of 10^(14-15) G. Only three such objects are known
in our Galaxy, and a fourth one is associated with the supernova remnant N49 in
the Large Magellanic Cloud. In none of these cases has an optical counterpart
to either the gamma-ray flares or the quiescent source been identified. Here we
present multi-wavelength observations of a puzzling source, SWIFT
J195509+261406, for which we detected more than 40 flaring episodes in the
optical band over a time span of 3 days, plus a faint infrared flare 11 days
later, after which it returned to quiescence. We propose that SWIFT
J195509+261406 is a member of a subgroup of SGRs for which the long-term X-ray
emission is transient in nature. Furthermore, it is the first SGR for which
bursts have been detected in the optical and near-infrared bands and maybe the
link between the "persistent" SGRs and the dim isolated neutron stars.Comment: Version submitted to Nature on 31 Jan 2008. A substantially revised
version of this work has been published in Nature, vol. 455 issue 7212 pp
506-509 under the title "Flares from a Galactic magnetar suggest a missing
link to dim isolated neutron stars
Participation of Actin on Giardia lamblia Growth and Encystation
BACKGROUND:Microfilaments play a determinant role in different cell processes such as: motility, cell division, phagocytosis and intracellular transport; however, these structures are poorly understood in the parasite Giardia lamblia. METHODOLOGY AND PRINCIPAL FINDINGS:By confocal microscopy using TRITC-phalloidin, we found structured actin distributed in the entire trophozoite, the label stand out at the ventral disc, median body, flagella and around the nuclei. During Giardia encystation, a sequence of morphological changes concurrent to modifications on the distribution of structured actin and in the expression of actin mRNA were observed. To elucidate whether actin participates actively on growth and encystation, cells were treated with Cytochalasin D, Latrunculin A and Jasplakinolide and analyzed by confocal and scanning electron microscopy. All drugs caused a growth reduction (27 to 45%) and changes on the distribution of actin. Besides, 60 to 80% of trophozoites treated with the drugs, exhibited damage at the caudal region, alterations in the flagella and wrinkles-like on the plasma membrane. The drugs also altered the cyst-yield and the morphology, scanning electron microscopy revealed diminished cytokinesis, cysts with damages in the wall and alterations in the size and on the intermembranal space. Furthermore, the drugs caused a significant reduction of the intensity of fluorescence-labeled CWP1 on ESV and on cyst wall, this was coincident with a reduction of CWP1 gene expression (34%). CONCLUSIONS AND SIGNIFICANCE:All our results, indicated an important role of actin in the morphology, growth and encystation and indirectly suggested an actin role in gene expression
Validation and atmospheric exploration of the sub-Neptune TOI-2136b around a nearby M3 dwarf
Context. The NASA space telescope TESS is currently in the extended mission of its all-sky search for new transiting planets. Of the thousands of candidates that TESS is expected to deliver, transiting planets orbiting nearby M dwarfs are particularly interesting targets since they provide a great opportunity to characterize their atmospheres by transmission spectroscopy. Aims. We aim to validate and characterize the new sub-Neptune-sized planet candidate TOI-2136.01 orbiting a nearby M dwarf (d = 33.36 +/- 0.02 pc, T-eff = 3373 +/- 108 K) with an orbital period of 7.852 days. Methods. We use TESS data, ground-based multicolor photometry, and radial velocity measurements with the InfraRed Doppler (IRD) instrument on the Subaru Telescope to validate the planetary nature of TOI-2136.01, and estimate the stellar and planetary parameters. We also conduct high-resolution transmission spectroscopy to search for helium in its atmosphere. Results. We confirm that TOI-2136.01 (now named TOI-2136b) is a bona fide planet with a planetary radius of R-p = 2.20 +/- 0.07 R-circle plus and a mass of M-p = 4.7(-2.6)(+3.1) M-circle plus. We also search for helium 10830 angstrom absorption lines and place an upper limit on the equivalent width of <7.8 m angstrom and on the absorption signal of <1.44% with 95% confidence. Conclusions. TOI-2136b is a sub-Neptune transiting a nearby and bright star (J = 10.8 mag), and is a potentially hycean planet, which is a new class of habitable planets with large oceans under a H-2-rich atmosphere, making it an excellent target for atmospheric studies to understand the formation, evolution, and habitability of the small planets
Discovery and Development of Toll-Like Receptor 4 (TLR4) Antagonists: A New Paradigm for Treating Sepsis and Other Diseases
Abstract. Sepsis remains the most common cause of death in intensive care units in the USA, with a current estimate of at least 750,000 cases per year, and 215,000 deaths annually. Despite extensive research still we do not quite understand the cellular and molecular mechanisms that are involved in triggering and propagation of septic injury. Endotoxin (lipopolysaccharide from Gram-negative bacteria, or LPS) has been implicated as a major cause of this syndrome. Inflammatory shock as a consequence of LPS release remains a serious clinical concern. In humans, inflammatory responses to LPS result in the release of cytokines and other cell mediators from monocytes and macrophages, which can cause fever, shock, organ failure and death. A number of different approaches have been investigated to try to treat and/or prevent the septic shock associated with infections caused by Gram-negative bacteria, including blockage of one or more of the cytokines induced by LPS. Recently several novel amphipathic compounds have been developed as direct LPS antagonists at the LPS receptor, TLR4. This review article will outline the current knowledge on the TLR4-LPS synthesis and discuss the signaling, in vitro pre-clinical and in vivo clinical evaluation of TLR4 antagonists and their potential use in sepsis and a variety of diseases such as atherosclerosis as well as hepatic and renal malfunction. KEY WORDS: drug discovery; LPS; sepsis; toll-like receptor antagonists
Three Short Period Jupiters from TESS
We report the confirmation and mass determination of three hot Jupiters
discovered by the Transiting Exoplanet Survey Satellite (TESS) mission: HIP
65Ab (TOI-129, TIC-201248411) is an ultra-short-period Jupiter orbiting a
bright (V=11.1 mag) K4-dwarf every 0.98 days. It is a massive 3.213 +/- 0.078
Mjup planet in a grazing transit configuration with an impact parameter of b =
1.17 +0.10/-0.08. As a result the radius is poorly constrained, 2.03
+0.61/-0.49 Rjup. The planet's distance to its host star is less than twice the
separation at which it would be destroyed by Roche lobe overflow. It is
expected to spiral into HIP 65A on a timescale ranging from 80 Myr to a few
gigayears, assuming a reduced tidal dissipation quality factor of Qs' = 10^7 -
10^9. We performed a full phase-curve analysis of the TESS data and detected
both illumination- and ellipsoidal variations as well as Doppler boosting. HIP
65A is part of a binary stellar system, with HIP 65B separated by 269 AU (3.95
arcsec on sky). TOI-157b (TIC 140691463) is a typical hot Jupiter with a mass
of 1.18 +/- 0.13 Mjup and a radius of 1.29 +/- 0.02 Rjup. It has a period of
2.08 days, which corresponds to a separation of just 0.03 AU. This makes
TOI-157 an interesting system, as the host star is an evolved G9 sub-giant star
(V=12.7). TOI-169b (TIC 183120439) is a bloated Jupiter orbiting a V=12.4
G-type star. It has a mass of 0.79 +/- 0.06 Mjup and a radius of 1.09
+0.08/-0.05 Rjup. Despite having the longest orbital period (P = 2.26 days) of
the three planets, TOI-169b receives the most irradiation and is situated on
the edge of the Neptune desert. All three host stars are metal rich with [Fe/H]
ranging from 0.18 - 0.24.Comment: Published in A&
- …