2,221 research outputs found
A conserved filamentous assembly underlies the structure of the meiotic chromosome axis.
The meiotic chromosome axis plays key roles in meiotic chromosome organization and recombination, yet the underlying protein components of this structure are highly diverged. Here, we show that 'axis core proteins' from budding yeast (Red1), mammals (SYCP2/SYCP3), and plants (ASY3/ASY4) are evolutionarily related and play equivalent roles in chromosome axis assembly. We first identify 'closure motifs' in each complex that recruit meiotic HORMADs, the master regulators of meiotic recombination. We next find that axis core proteins form homotetrameric (Red1) or heterotetrameric (SYCP2:SYCP3 and ASY3:ASY4) coiled-coil assemblies that further oligomerize into micron-length filaments. Thus, the meiotic chromosome axis core in fungi, mammals, and plants shares a common molecular architecture, and likely also plays conserved roles in meiotic chromosome axis assembly and recombination control
New cytogenetic prognostic markers in breast cancer
Abstract
BACKGROUND:
The aim of this study was to identify chromosomal imbalances in a series of invasive ductal carcinomas. In order to characterize the prognostic value of the chromosomal aberrations, we determined the association between genetic changes, overall survival, recurrences and some well-known prognostic and diagnostic parameters.
MATERIAL AND METHODS:
We included in this study 70 ductal invasive carcinomas diagnosed at the Hospital of Navarra during 1991-1994. We used the Comparative Genomic Hybridization Technique (CGH) for the molecular cytogenetic analysis of formalin-fixed, paraffin embedded specimens.
RESULTS:
We obtained successful results in 57 out of 70 cases (81.4%). The most frequent recurring findings were DNA gains on 8q, 17q, 1q, 20q, 11q and 6q and losses on 16q, Xp, Xq, 13q, 11q and 8p. In the survival study, gains on 1q and 11q13 were more frequent in patients with recurrence (41.3% vs. 18.5% and 50% vs. 23.7%). Loss of 16q appears as a prognostic factor of good outcome because of its association with good pathological prognostic features: 100% of tumors with this aberration showed overexpression of Bcl-2, and 75% of them were node negative. Besides, 46.7% of the positive cases for the expression of estrogen receptors also showed this imbalance.
CONCLUSIONS:
The CGH is a useful technique for the study of paraffin embedded tumors. Our results confirm that the cytogenetic aberrations of tumors could be considered as prognostic factors contributing to a better knowledge of tumor outcome
Genomic imbalances detected by comparative genomic hybridization are prognostic markers in invasive ductal breast carcinomas
AIMS:
The aim of this work is the study of the prognostic significance of the chromosomal aberrations described in a series of invasive ductal breast carcinomas.
METHODS AND RESULTS:
We analysed by comparative genomic hybridization a group of 70 formalin-fixed paraffin-embedded invasive ductal breast carcinomas. Aberrations showed a frequency similar to previous studies using frozen tumours. Interestingly, we identified gains involving 6q16-q24 more frequently than in other series. We analysed the association among the chromosomal imbalances, 11 histopathological factors, relapse rate and overall survival of patients. Associations showed 16q losses as a potential marker of good prognosis, as they were more frequent in node-negative (P=0.025) and in oestrogen-positive tumours (P < 0.001). Furthermore, 100% of bcl-2+ tumours presented this aberration compared with 29.3% in bcl-2- (P=0.014). 1q, 11q, 17q and 20q gains were associated with poor prognosis: 95% of cases with 1q gains were bigger than 20 mm (P=0.041). Tumours with 1q and 11q gains showed a higher relapse rate (P=0.063; P=0.066). Within the good prognosis group of lymph node-negative patients, 17q and 20q gains identify a subgroup with increased relapse rate (P=0.039).
CONCLUSIONS:
Chromosomal imbalances, together with histopathological factors, may help to predict outcome in breast cancer patients
Physiological Status Drives Metabolic Rate in Mediterranean Geckos Infected with Pentastomes
Negative effects of parasites on their hosts are well documented, but the proximate mechanisms by which parasites reduce their host's fitness are poorly understood. For example, it has been suggested that parasites might be energetically demanding. However, a recent meta-analysis suggests that they have statistically insignificant effects on host resting metabolic rate (RMR). It is possible, though, that energetic costs associated with parasites are only manifested during and/or following periods of activity. Here, we measured CO2 production (a surrogate for metabolism) in Mediterranean geckos (Hemidactylus turcicus) infected with a lung parasite, the pentastome Raillietiella indica, under two physiological conditions: rested and recently active. In rested geckos, there was a negative, but non-significant association between the number of pentastomes (i.e., infection intensity) and CO2 production. In recently active geckos (chased for 3 minutes), we recorded CO2 production from its maximum value until it declined to a stationary phase. We analyzed this decline as a 3 phase function (initial decline, secondary decline, stationary). Geckos that were recently active showed, in the secondary phase, a significant decrease in CO2 production as pentastome intensity increased. Moreover, duration of the secondary phase showed a significant positive association with the number of pentastomes. These results suggest that the intensity of pentastome load exerts a weak effect on the metabolism of resting geckos, but a strong physiological effect on geckos that have recently been active; we speculate this occurs via mechanical constraints on breathing. Our results provide a potential mechanism by which pentastomes can reduce gecko fitness
A conserved filamentous assembly underlies the structure of the meiotic chromosome axis
The meiotic chromosome axis plays key roles in meiotic chromosome organization and recombination, yet the underlying protein components of this structure are highly diverged. Here, we show that 'axis core proteins' from budding yeast (Red1), mammals (SYCP2/SYCP3), and plants (ASY3/ASY4) are evolutionarily related and play equivalent roles in chromosome axis assembly. We first identify 'closure motifs' in each complex that recruit meiotic HORMADs, the master regulators of meiotic recombination. We next find that axis core proteins form homotetrameric (Red1) or heterotetrameric (SYCP2:SYCP3 and ASY3:ASY4) coiled-coil assemblies that further oligomerize into micron-length filaments. Thus, the meiotic chromosome axis core in fungi, mammals, and plants shares a common molecular architecture, and likely also plays conserved roles in meiotic chromosome axis assembly and recombination control
The afterglow and kilonova of the short GRB 160821B
GRB 160821B is a short duration gamma-ray burst (GRB) detected and localized
by the Neil Gehrels Swift Observatory in the outskirts of a spiral galaxy at
z=0.1613, at a projected physical offset of 16 kpc from the galaxy's center. We
present X-ray, optical/nIR and radio observations of its counterpart and model
them with two distinct components of emission: a standard afterglow, arising
from the interaction of the relativistic jet with the surrounding medium, and a
kilonova, powered by the radioactive decay of the sub-relativistic ejecta.
Broadband modeling of the afterglow data reveals a weak reverse shock
propagating backward into the jet, and a likely jet-break at 3.5 d. This is
consistent with a structured jet seen slightly off-axis while expanding into a
low-density medium. Analysis of the kilonova properties suggests a rapid
evolution toward red colors, similar to AT2017gfo, and a low nIR luminosity,
possibly due to the presence of a long-lived neutron star. The global
properties of the environment, the inferred low mass (M_ej < 0.006 Msun) and
velocities (v > 0.05 c) of lanthanide-rich ejecta are consistent with a binary
neutron star merger progenitor.Comment: 14 pages, 6 figures, MNRAS, in press. Moderate revision, added Figure
5 and X-ray data to Table
Description of the exposure of the most-followed spanish instamom's children to social medias
There is evidence of the risk of overexposure of children on social networks by parents working as influencers. A cross-sectional study of the profiles of the sixteen most-followed Instamoms in Spain was carried out. An analysis of these profiles was performed over a full month (April 2022), three times a week, to describe the representation of influencers’ children in the posts shared by them, as well as their role in the Instamoms’ marketing. A total of 192 evaluations of the profiles were performed in the study period. The average number of children exposed by an Instamom was three, generally preschoolers and schoolchildren. The children appear in a context of the family home and accompanied by their mother. The type of advertising that accompanies the appearance of underage children is usually women or children’s clothing, but also food products, leisure, etc. Appearance of children in the posts had a statistically significant influence on followers measured by the number of likes. Results provided the identification of two Instamom clusters with differentiated behaviors in relation to appearance of children in posts. It is important to involve Social Pediatrics in the protection of the privacy and interests of children given the increase in sharenting. The authors believe that there are concerns about their explicit consent to public exposure from early childhood and about the medium and long-term effect that this may have on their future well-being
Prognostic ability of EndoPredict compared to research-based versions of the PAM50 risk of recurrence (ROR) scores in node-positive, estrogen receptor-positive, and HER2-negative breast cancer. A GEICAM/9906 sub-study
There are several prognostic multigene-based tests for managing breast cancer (BC), but limited data comparing them in the same cohort. We compared the prognostic performance of the EndoPredict (EP) test (standardized for pathology laboratory) with the research-based PAM50 non-standardized qRT-PCR assay in node-positive estrogen receptor-positive (ER+) and HER2-negative (HER2−) BC patients receiving adjuvant chemotherapy followed by endocrine therapy (ET) in the GEICAM/9906 trial. EP and PAM50 risk of recurrence (ROR) scores [based on subtype (ROR-S) and on subtype and proliferation (ROR-P)] were compared in 536 ER+/HER2− patients. Scores combined with clinical information were evaluated: ROR-T (ROR-S, tumor size), ROR-PT (ROR-P, tumor size), and EPclin (EP, tumor size, nodal status). Patients were assigned to risk-categories according to prespecified cutoffs. Distant metastasis-free survival (MFS) was analyzed by Kaplan–Meier. ROR-S, ROR-P, and EP scores identified a low-risk group with a relative better outcome (10-year MFS: ROR-S 87%; ROR-P 89%; EP 93%). There was no significant difference between tests. Predictors including clinical information showed superior prognostic performance compared to molecular scores alone (10-year MFS, low-risk group: ROR-T 88%; ROR-PT 92%; EPclin 100%). The EPclin-based risk stratification achieved a significantly improved prediction of MFS compared to ROR-T, but not ROR-PT. All signatures added prognostic information to common clinical parameters. EPclin provided independent prognostic information beyond ROR-T and ROR-PT. ROR and EP can reliably predict risk of distant metastasis in node-positive ER+/HER2− BC patients treated with chemotherapy and ET. Addition of clinical parameters into risk scores improves their prognostic ability.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-016-3725-z) contains supplementary material, which is available to authorized users
Preanalytical issues related to routine and diagnostic glucose tests: Results from a survey in Spain
Introduction: Diabetes mellitus (DM) is one of the most prevalent diseases worldwide. The objective of this study was to find out under what preanalytical conditions routine and diagnostic glucose tests are performed across Spanish laboratories; and also what criteria are used for DM diagnosis.
Materials and methods: An online survey was performed by the Commission on Quality Assurance in the Extra-Analytical Phase of the Spanish
Society of Laboratory Medicine (SEQC-ML). Access to the questionnaire was available on the home page of the SEQC-ML website during the period
April-July 2018. Data analysis was conducted with the IBM SPSS© Statistics (version 20.0) program.
Results: A total of 96 valid surveys were obtained. Most laboratories were in public ownership, serving hospital and primary care patients, with
high and medium workloads, and a predominance of mixed routine-urgent glucose testing. Serum tubes were the most used for routine glucose
analysis (92%) and DM diagnosis (54%); followed by lithium-heparin plasma tubes (62%), intended primarily for urgent glucose testing; point-ofcare testing devices were used by 37%; and plasma tubes with a glycolysis inhibitor, mainly sodium fluoride, by 19%. Laboratories used the cut-off
values and criteria recognized worldwide for DM diagnosis in adults and glucose-impaired tolerance, but diverged in terms of fasting plasma glucose
and gestational DM criteria.
Conclusion: Preanalytical processing of routine and DM diagnostic glucose testing in Spain does not allow a significant, non-quantified influence of
glycolysis on the results to be ruled out. Possible adverse consequences include a delay in diagnosis and possible under-treatmen
Pulse phase resolved analysis of the HMXB Cen X-3 over two binary orbits
We present a detailed analysis of observations of the high mass X-ray binary
Cen X-3 spanning two consecutive binary orbits performed with the RXTE
satellite in early March 1997. The PCA and HEXTE light curves both show a clear
reduction in count rate after mid-orbit for both binary revolutions. We
therefore analyze two broad band spectra for each orbit, before and after
mid-orbit. Consistent with earlier observations these four joint PCA and HEXTE
spectra can be well described using a phenomenological pulsar continuum model,
including an iron emission line and a cyclotron resonance scattering feature.
While no strong spectral variations were detected, the second half of orbit 2
shows a tendency toward being softer and more strongly absorbed. In order to
follow the orbital phase-dependent evolution of the spectrum in greater detail,
we model spectra for shorter exposures, confirming that most spectral
parameters show either a gradual or sudden change for the second half of the
second orbit. A comparison with a simple wind model indicates the existence of
an accretion wake in this system. We also present and discuss high resolution
pulse profiles for several different energy bands, as well as their hardness
ratios. PCA and HEXTE spectra were created for 24 phase bins and fitted using
the same model as in the phase averaged case. Systematic pulse phase-dependent
variations of several continuum and cyclotron line parameters were detected,
most notably a significant increase of the cyclotron line energy during the
early rise of the main peak, followed by a gradual decrease. We show that
applying a simple dipole model for the magnetic field is not sufficient to
describe our data.Comment: 12 pages, 9 figures, accepted for publication in Ap
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