The microscopic environment inside a metazoan organism is highly crowded. Whether individual cells can tailor their behavior to the limited space remains unclear. In this study, we found that cells ...measure the degree of spatial confinement by using their largest and stiffest organelle, the nucleus. Cell confinement below a resting nucleus size deforms the nucleus, which expands and stretches its envelope. This activates signaling to the actomyosin cortex via nuclear envelope stretch-sensitive proteins, up-regulating cell contractility. We established that the tailored contractile response constitutes a nuclear ruler-based signaling pathway involved in migratory cell behaviors. Cells rely on the nuclear ruler to modulate the motive force that enables their passage through restrictive pores in complex three-dimensional environments, a process relevant to cancer cell invasion, immune responses, and embryonic development.
Background: Liver biopsy is an invasive technique with associated major complications. There is no information on the validity of five non-invasive indexes based on routinely available parameters, ...estimated and validated in hepatitis C virus (HCV) monoinfected patients, in human immunodeficiency virus (HIV)/HCV coinfected patients. Aim: To validate these predictive models of liver fibrosis in HIV/HCV coinfected patients. Patients: A total of 357 (90%) of 398 patients from five hospitals were investigated, who underwent liver biopsy and who had complete data to validate all of the models considered. Methods: The predictive accuracy of the indexes was tested by measuring areas under the receiver operating characteristic curves. Diagnostic accuracy was calculated by estimating sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values. Results: The models performed better when liver biopsies ⩾15 mm were used as reference. In this setting, the Forns and Wai indexes, models aimed at discriminating significant fibrosis, showed PPV of 94% and 87%, respectively. Using these models, 27–34% of patients could benefit from exclusion of liver biopsy. If both models were applied sequentially, 41% of liver biopsies could be spared. The indexes aimed at predicting cirrhosis achieved NPV of up to 100%. However, they showed very low PPV. Conclusions: The diagnostic accuracy of these models was lower in HIV/HCV coinfected patients than in the validation studies performed in HCV monoinfected patients. However, simple fibrosis tests may render liver biopsy unnecessary in deciding anti-HCV treatment in over one third of patients with HIV infection and chronic hepatitis C.
Local dwarf spheroidal galaxies (dSphs) are nearby dark-matter dominated systems, making them excellent targets for searching for gamma rays from particle dark matter interactions. If dark matter ...annihilates or decays directly into two gamma rays (or a gamma ray and a neutral particle), a monochromatic spectral line is created. At TeV energies, no other process is predicted to produce spectral lines, making this a very clean indirect dark matter search channel. With the development of event-by-event energy reconstruction, we can now search for spectral lines with the High Altitude Water Cherenkov (HAWC) Observatory. HAWC is a wide field of view survey instrument located in central Mexico that observes gamma rays from ∼ 200 GeV to ∼ 200 TeV . In this work we present results from a recent search for spectral lines from local, dark matter dominated, dwarf galaxies using 1038 days of HAWC data. We also present updated limits on several continuum channels that were reported in a previous publication. Our gamma-ray spectral line limits are the most constraining obtained so far from 20 TeV to 100 TeV.
We present the first catalog of gamma-ray sources emitting above 56 and 100 TeV with data from the High Altitude Water Cherenkov Observatory, a wide field-of-view observatory capable of detecting ...gamma rays up to a few hundred TeV. Nine sources are observed above 56 TeV, all of which are likely galactic in origin. Three sources continue emitting past 100 TeV, making this the highest-energy gamma-ray source catalog to date. We report the integral flux of each of these objects. We also report spectra for three highest-energy sources and discuss the possibility that they are PeVatrons.
The extragalactic background light (EBL) is of fundamental importance both for understanding the entire process of galaxy evolution and for γ-ray astronomy, but the overall spectrum of the EBL ...between 0.1 and 1000 μm has never been determined directly from galaxy spectral energy distribution (SED) observations over a wide redshift range. The evolving, overall spectrum of the EBL is derived here utilizing a novel method based on observations only. This is achieved from the observed evolution of the rest-frame K-band galaxy luminosity function up to redshift 4, combined with a determination of galaxy-SED-type fractions. These are based on fitting Spitzer Wide-Area Infrared Extragalactic Survey (SWIRE) templates to a multiwavelength sample of about 6000 galaxies in the redshift range from 0.2 to 1 from the All-wavelength Extended Groth Strip International Survey (AEGIS). The changing fractions of quiescent galaxies, star-forming galaxies, starburst galaxies and active galactic nucleus (AGN) galaxies in that redshift range are estimated, and two alternative extrapolations of SED types to higher redshifts are considered. This allows calculation of the evolution of the luminosity densities from the ultraviolet (UV) to the infrared (IR), the evolving star formation rate density of the Universe, the evolving contribution to the bolometric EBL from the different galaxy populations including AGN galaxies and the buildup of the EBL. Our EBL calculations are compared with those from a semi-analytic model, another observationally based model and observational data. The EBL uncertainties in our modelling based directly on the data are quantified, and their consequences for attenuation of very-high-energy γ-rays due to pair production on the EBL are discussed. It is concluded that the EBL is well constrained from the UV to the mid-IR, but independent efforts from IR and γ-ray astronomy are needed in order to reduce the uncertainties in the far-IR.
We analyze the Sun as a source for the indirect detection of dark matter through a search for gamma rays from the solar disk. Capture of dark matter by elastic interactions with the solar nuclei ...followed by annihilation to long-lived mediators can produce a detectable gamma-ray flux. We search 3 years of data from the High Altitude Water Cherenkov (HAWC) observatory and find no statistically significant detection of TeV gamma-ray emission from the Sun. Using this, we constrain the spin-dependent elastic scattering cross section of dark matter with protons for dark matter masses above 1 TeV, assuming a sufficiently long-lived mediator. The results complement constraints obtained from Fermi-LAT observations of the Sun and together cover WIMP masses between 4 and 106 GeV . In the optimal scenario, the cross-section constraints for mediator decays to gamma rays can be as strong as ∼ 10−45 cm2 , which is more than 4 orders of magnitude stronger than current direct-detection experiments for a 1 TeV dark matter mass. The cross-section constraints at higher masses are even better, nearly 7 orders of magnitude better than the current direct-detection constraints for a 100 TeV dark matter mass. This demonstration of sensitivity encourages detailed development of theoretical models in light of these powerful new constraints.
Composting has been traditionally considered a process in which a succession of mesophilic and thermophilic microbial populations occurs due to temperature changes. In order to deepen in this model, ...1380 bacterial and fungal strains (the entire culturable microbiota isolated from a composting process) were investigated for their ability to grow across a wide range of temperatures (20 to 60 °C). First, qualitative tests were performed to establish a thermal profile for each strain. Then, quantitative tests allowed ascertaining the extent of growth for each strain at each of the tested temperatures. The identity of the isolates enabled to position them taxonomically and permitted tracking the strains throughout the process. Results showed that 90% of the isolates were classified as thermotolerant (they grew at all tested temperatures). Only 9% and 1% of the studied strains showed to be strictly mesophilic or thermophilic, respectively. Firmicutes exhibited the greatest thermal plasticity, followed by Actinobacteria and Ascomycota. Most of the Proteobacteria and all Basidiomycota strains were also able to grow at all the assayed temperatures. Thermotolerance was clearly demonstrated among the composting microbiota, suggesting that the idea of the succession of mesophilic and thermophilic populations throughout the process might need a reassessment.
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•The temperature-driven succession of the composting microbial populations was revisited.•Thermotolerance was demonstrated for a vast majority of the composting microbiota.•Thermotolerant strains were repeatedly identified in most of the composting stages.•Firmicutes and Ascomycota accounted for the best represented thermotolerant phyla.•Thermal plasticity is a microbial reply to the ever changing composting conditions.
The extent and nature of symbolic behavior among Neandertals are obscure. Although evidence for Neandertal body ornamentation has been proposed, all cave painting has been attributed to modern ...humans. Here we present dating results for three sites in Spain that show that cave art emerged in Iberia substantially earlier than previously thought. Uranium-thorium (U-Th) dates on carbonate crusts overlying paintings provide minimum ages for a red linear motif in La Pasiega (Cantabria), a hand stencil in Maltravieso (Extremadura), and red-painted speleothems in Ardales (Andalucía). Collectively, these results show that cave art in Iberia is older than 64.8 thousand years (ka). This cave art is the earliest dated so far and predates, by at least 20 ka, the arrival of modern humans in Europe, which implies Neandertal authorship.
Gastric carcinoma (GC) with second primary malignancy (SPM) is the most frequent combination within the multiple primary malignancies (MPM) group. The presentation of a GC associated with a ...synchronized SPM in the kidney is extremely rare and unusual. This study presents a rare case of synchronous tumors, describes the main associated risk factors, and emphasizes the need to rule out SPM.
We present the case of a 63-year-old Hispanic woman with a history of smoking, weight loss, and gastrointestinal (GI) bleeding. GC was diagnosed by endoscopy, and during her workup for metastatic disease, a synchronous SPM was noted in the left kidney. The patient underwent resection of both tumors with a satisfactory postoperative course. A systematic review of the literature was performed using the Medline/PubMed, Science Direct, Scopus, and Google Scholar databases. A search of the literature yielded 13 relevant articles, in which the following main risk factors were reported: the treatment utilized, the grade and clinical stage, histopathological report, and in some cases survival. It is concluded that advanced age (> 60 years) and smoking are the main associated risk factors.
Gastric carcinoma is the second most frequent neoplasm of the GI tract and the main neoplasm that presents a SPM. MPM screening is recommended in patients with gastric cancer. The clinical discovery of MPM of renal origin is rare and hence the importance of the current report.
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