Significance
The detection of ethanolamine (
N
H
2
C
H
2
C
H
2
OH) in a molecular cloud in the interstellar medium confirms that a precursor of phospholipids is efficiently formed by interstellar ...chemistry. Hence, ethanolamine could have been transferred from the proto-Solar nebula to planetesimals and minor bodies of the Solar System and thereafter to our planet. The prebiotic availability of ethanolamine on early Earth could have triggered the formation of efficient and permeable amphiphilic molecules such as phospholipids, thus playing a relevant role in the evolution of the first cellular membranes needed for the emergence of life.
Cell membranes are a key element of life because they keep the genetic material and metabolic machinery together. All present cell membranes are made of phospholipids, yet the nature of the first membranes and the origin of phospholipids are still under debate. We report here the presence of ethanolamine in space,
N
H
2
C
H
2
C
H
2
OH, which forms the hydrophilic head of the simplest and second-most-abundant phospholipid in membranes. The molecular column density of ethanolamine in interstellar space is
N
= (1.51
±
0.07)
×
10
13
c
m
−
2
, implying a molecular abundance with respect to
H
2
of
(
0.9
−
1.4
)
×
10
−
10
. Previous studies reported its presence in meteoritic material, but they suggested that it is synthesized in the meteorite itself by decomposition of amino acids. However, we find that the proportion of the molecule with respect to water in the interstellar medium is similar to the one found in the meteorite (
10
−
6
). These results indicate that ethanolamine forms efficiently in space and, if delivered onto early Earth, could have contributed to the assembling and early evolution of primitive membranes.
One of the proposed scenarios for the origin of life is the primordial RNA world, which considers that RNA molecules were likely responsible for the storage of genetic information and the catalysis ...of biochemical reactions in primitive cells, before the advent of proteins and DNA. In the last decade, experiments in the field of prebiotic chemistry have shown that RNA nucleotides can be synthesized from relatively simple molecular precursors, most of which have been found in space. An important exception is hydroxylamine, NH2OH, which, despite several observational attempts, it has not been detected in space yet. Here we present the first detection of NH2OH in the interstellar medium toward the quiescent molecular cloud G+0.693-0.027 located in the Galactic Center. We have targeted the three groups of transitions from the J = 2−1, 3−2, and 4−3 rotational lines, detecting five transitions that are unblended or only slightly blended. The derived molecular abundance of NH2OH is (2.1 0.9) × 10−10. From the comparison of the derived abundance of NH2OH and chemically related species, with those predicted by chemical models and measured in laboratory experiments, we favor the formation of NH2OH in the interstellar medium via hydrogenation of NO on dust grain surfaces, with possibly a contribution of ice-mantle NH3 oxidation processes. Further laboratory studies and quantum chemical calculations are needed to completely rule out the formation of NH2OH in the gas phase.
The chemical compounds carrying the thiol group (-SH) have been considered essential in recent prebiotic studies regarding the polymerization of amino acids. We have searched for this kind of ...compound toward the Galactic Center quiescent cloud G+0.693–0.027. We report the first detection in the interstellar space of the trans-isomer of monothioformic acid (t-HC(O)SH) with an abundance of ∼1 נ10−10. Additionally, we provide a solid confirmation of the gauche isomer of ethyl mercaptan (g-C2H5SH) with an abundance of ∼3 נ10−10, and we also detect methyl mercaptan (CH3SH) with an abundance of ∼5 נ10−9. Abundance ratios were calculated for the three SH-bearing species and their OH analogs, revealing similar trends between alcohols and thiols with increasing complexity. Possible chemical routes for the interstellar synthesis of t-HC(O)SH, CH3SH, and C2H5SH are discussed, as well as the relevance of these compounds in the synthesis of prebiotic proteins in the primitive Earth.
Abstract
Amines, particularly primary amines (R-NH
2
), are closely related to the primordial synthesis of amino acids since they share the same structural backbone. However, only a limited number of ...amines has been identified in the interstellar medium, which prevents us from studying their chemistry as well as their relation to prebiotic species that could lead to the emergence of life. In this Letter, we report the first interstellar detection of vinylamine (C
2
H
3
NH
2
) and tentative detection of ethylamine (C
2
H
5
NH
2
) toward the Galactic center cloud G+0.693-0.027. The derived abundance with respect to H
2
is (3.3 ± 0.4) × 10
−10
and (1.9 ± 0.5) × 10
−10
, respectively. The inferred abundance ratios of C
2
H
3
NH
2
and C
2
H
5
NH
2
with respect to methylamine (CH
3
NH
2
) are ∼0.02 and ∼0.008, respectively. The derived abundance of C
2
H
3
NH
2
, C
2
H
5
NH
2
, and several other NH
2
-bearing species are compared to those obtained toward high-mass and low-mass star-forming regions. Based on recent chemical and laboratory studies, possible chemical routes for the interstellar synthesis of C
2
H
3
NH
2
and C
2
H
5
NH
2
are discussed.
For better management of patients with febrile neutropenia, our study investigated the epidemiologic, microbiologic, and clinical characteristics of adult inpatients with febrile neutropenia and ...their mortality-associated factors. To this end, we carried out a prospective, observational, multicenter study in 28 Argentinian hospitals between 2007 and 2012. We included 515 episodes of febrile neutropenia from 346 patients, median age 49 years. Neutropenia followed chemotherapy in 77% of cases, half of the cases due to hematological malignancies. Most episodes were classified as high-risk according to MASCC criteria, and 53.6% of patients were already hospitalized at the onset of febrile neutropenia. Bloodstream infections were detected in 14% episodes; whereas an infectious source of fever was identified in 80% of cases. Mortality rate achieved to 14.95%. The binary regression analysis showed that persistence of fever at day 7, or neutropenia at day 14, dehydration and tachycardia at the onset of febrile neutropenia as well as prior infections were significantly associated with mortality. In addition to expanding our current knowledge on the features of adult patients with febrile neutropenia, present findings provide useful information for better management of them in Argentina, given the appropriate representativeness of centers participating in the study.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Context.
Theories of the origins of life propose that early cell membranes were synthesised from amphiphilic molecules simpler than phospholipids, such as fatty alcohols. The discovery in the ...interstellar medium (ISM) of ethanolamine, the simplest phospholipid head group, raises the question whether simple amphiphilic molecules are also synthesised in space.
Aims.
We investigate whether precursors of fatty alcohols are present in the ISM.
Methods.
To do this, we have carried out a spectral survey at 7, 3, 2 and 1 mm towards the Giant Molecular Cloud G+0.693-0.027 located in the Galactic centre using the IRAM 30 m and Yebes 40 m telescopes.
Results.
Here, we report the detection in the ISM of the primary alcohol
n
-propanol (in both conformers
Ga
-
n
-C
3
H
7
OH and
Aa
-
n
-C
3
H
7
OH), a precursor of fatty alcohols. The derived column densities of
n
-propanol are (5.5 ± 0.4) × 10
13
cm
−2
for the
Ga
conformer and (3.4 ± 0.3) × 10
13
cm
−2
for the
Aa
conformer, which imply molecular abundances of (4.1 ± 0.3) × 10
−10
for
Ga
-
n
-C
3
H
7
OH and of (2.5 ± 0.2) × 10
−10
for
Aa
-
n
-C
3
H
7
OH. We also searched for the
AGa
conformer of
n
-butanol
AGa
-
n
-C
4
H
9
OH without success, yielding an upper limit to its abundance of ≤4.1 × 10
−11
. The inferred CH
3
OH:C
2
H
5
OH:C
3
H
7
OH:C
4
H
9
OH abundance ratios are 1:0.04:0.006:≤0.0004 towards G+0.693-0.027, that is, they decrease roughly by one order of magnitude for increasing complexity. We also report the detection of both syn and anti conformers of vinyl alcohol, with column densities of (1.11 ± 0.08) × 10
14
cm
−2
and (1.3 ± 0.4) × 10
13
cm
−2
, and abundances of (8.2 ± 0.6) × 10
−10
and (9.6 ± 3.0) × 10
−11
, respectively.
Conclusions.
The detection of
n
-propanol, together with the recent discovery of ethanolamine in the ISM, opens the possibility that precursors of lipids according to theories of the origin of life, could have been brought to Earth from outer space.
Migration of nib Cd to the testa during fermentation can be achieved with high temperatures (> 45 °C) and low nib pH values (< 5.0) using spontaneous fermentation. However, this low pH can lead to ...low flavor quality. This study used three controlled temperature fermentation treatments on three cacao genotypes (CCN 51, ICS 95, and TCS 01) to test its effects on the nib pH, the migration of nib Cd to the testa, and the liquor flavor quality. All treatments were effective in reducing the total nib Cd concentration. Nevertheless, the treatment with the higher mean temperature (44.25 °C) and acidification (pH 4.66) reached the highest mean nib Cd reductions throughout fermentation, a 1.37 factor in TCS 01, promoting the development of fine-flavor cocoa sensorial notes. In unfermented beans, the Cd concentration of nibs was higher than that of the testa, and the Cd migration proceeded down the total concentration gradient. However, Cd migration was observed against the concentration gradient (testa Cd > nib Cd) from the fourth day. Cd migration could increase by extensive fermentation until the sixth day in high temperatures and probably by the adsorbent capacity of the testa. Genotype-by-treatment interactions were present for the nib Cd reduction, and a universal percentage of decrease of Cd for each genotype with fermentation cannot be expected. Selecting genotypes with highly adsorbent testa combined with controlled temperatures would help reduce the Cd concentration in the cacao raw material, improving its safety and quality.
Abstract
The Central Molecular Zone (CMZ) contains most of the mass of our Galaxy but its star formation rate is one order of magnitude lower than in the Galactic disk. This is likely related to the ...fact that the bulk of the gas in the CMZ is in a warm (>100 K) and turbulent phase with little material in the prestellar phase. We present in this Letter observations of deuterium fractionation (D/H ratios) of HCN, HNC, HCO
+
, and N
2
H
+
toward the CMZ molecular cloud G+0.693–0.027. These observations clearly show, for the first time, the presence of a colder, denser, and less turbulent narrow component, with a line width of ∼9 km s
−1
, in addition to the warm, less dense, and turbulent broad component with a line width of ∼20 km s
−1
. The very low D/H ratio ≤6 × 10
−5
for HCO
+
and N
2
H
+
, close to the cosmic value (∼2.5 × 10
−5
), and the high D/H ratios, >4 × 10
−4
for HCN and HNC, derived for the broad component confirm the presence of high-temperature deuteration routes for nitriles. For the narrow component we have derived D/H ratios >10
−4
and excitation temperatures of 7 K for all molecules, suggesting kinetic temperatures ≤30 K and H
2
densities ≥5 × 10
4
cm
−3
, at least one order of magnitude larger than that for the broad component. The method presented in this Letter allows us to identify clouds on the verge of star formation, i.e., under prestellar conditions, toward the CMZ. This method can also be used for the identification of such clouds in external galaxies.
Improving the binding of metal complexes to DNA to boost cancer cell cytotoxicity requires fine tuning of their structural and chemical properties. Copper has been used as a metal center in compounds ...containing intercalating ligands due to its ability to catalytically generate reactive oxygen species (ROS), such as hydroxyl radicals (OH&z.rad;). We envision the synergy of DNA binding and ROS generation in proximity to target DNA as a powerful chemotherapy treatment. Here, we explore the use of Cu(2CP-Bz-SMe)
2+
(2CP-Bz-SMe = 1,3-bis(1,10-phenanthrolin-2-yloxy)-
N
-(4-(methylthio)benzylidene)propan-2-amine) for this purpose by characterizing its cytotoxicity, DNA binding, and ability to affect DNA replication through the polymerase chain reaction - PCR and nuclease assays. We determined the binding (
K
b
) and Stern-Volmer constants (
K
SV
) for complex-DNA association of 5.8 ± 0.14 × 10
4
and 1.64 (±0.08), respectively, through absorption titration and competitive fluorescence experiments. These values were superior to those of other Cu-complex intercalators. We hypothesize that the distorted trigonal bipyramidal geometry of Cu(2CP-Bz-SMe)
2+
allows the phenanthroline fragments to be better accommodated into the DNA double helix. Moreover, the aromaticity of these fragments increases the local hydrophobicity thus increasing the affinity for the hydrophobic domains of DNA. Nuclease assays in the presence of common reducing agents ascorbic acid, nicotinamide adenine dinucleotide, and glutathione showed the effective degradation of DNA due to the
in situ
generation of OH&z.rad;. The Cu(2CP-Bz-SMe)
2+
complex showed cytotoxicity against the following human cancer cells lines A549, MCF-7, MDA-MB-231 and MG-63 with half maximal inhibitory concentration (IC
50
) values of 4.62 ± 0.48, 5.20 ± 0.76, 5.70 ± 0.42 and 2.88 ± 0.66 μM, respectively. These low values of IC
50
, which are promising if compared to that of cisplatin, are ascribed to the synergistic effect of ROS generation with the intercalation ability into the DNA minor grooves and blocking DNA replication. This study introduces new principles for synergizing the chemical and structural properties of intercalation compounds for improved drug-DNA interactions targeting cancer.
Attack cancer cells by different mechanisms of action, improves the activity of a compound as an anticancer drug.
The recently reported two-dimensional discrete perturbation theory for soft atomic fluids has been extended here for molecular fluids. In particular, the analytical expression for the Helmholtz free ...energy of intermolecular potentials of arbitrary profile is built within a discrete perturbation theory constructed with a sequence of two-dimensional (2D) square-well and square-shoulder potentials of variable effective widths and ranges. Fluids that comprised both convex and dumbbell particles have been considered. For the former ones, the equation of state was obtained as a function of density, temperature and intermolecular parameters with implicit shape dependence evaluated by a virial rescaling procedure from the compressibility factor of effective hard-disk and two-dimensional square-well/square-shoulder discrete potentials. By varying the intermolecular parameters through their geometrical dependence, some illustrative cases of 2D-square-well and Kihara spherocylinder fluids are explored, and their vapor-liquid phase diagrams and equations of state are tested against new simulation data. For the latter one, an available hard-dumbbell equation of state constitutes the reference term of the perturbation expansion. It is found that these theoretical approaches are able to reproduce the equations of state of the selected fluids quantitatively, but the vapor-liquid equilibrium is only grasped in a qualitative way. Reasons for this drawback are also discussed.
•A generalized two-dimensional discrete perturbation theory is developed for molecular fluids.•Phase diagrams and equations of state are tested against simulation data.•This theoretical framework can be easily updated after the report of new analytical theories for the liquid structure.•The theory can be extended to d-dimensional molecular fluids.
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