CO Tully–Fisher relation of star-forming galaxies at = 0.05–0.3

The Tully–Fisher relation (TFR) is an empirical relation between galaxy luminosity and rotation velocity. We present here the first TFR of galaxies beyond the local Universe that uses carbon monoxide (CO) as the kinematic tracer. Our final sample includes 25 isolated, non-interacting star-forming galaxies with double-horned or boxy CO integrated line profiles located at redshifts z ≤ 0.3, drawn from a larger ensemble of 67 detected objects. The best reverse Ks-band, stellar mass and baryonic mass CO TFRs are, respectively, MKs = (−8.4 ± 2.9)[log ( W50/km s−1 sin i ) − 2.5] + (−23.5 ± 0.5), log (M/M) = (5.2 ± 3.0)[log ( W50/km s−1 sin i ) − 2.5] + (10.1 ± 0.5) and log (Mb/M) = (4.9 ± 2.8)[log ( W50/km s−1 sin i ) − 2.5] + (10.2 ± 0.5), where MKs is the total absolute Ks-band magnitude of the objects, M and Mb their total stellar and baryonic masses, and W50 the width of their line profile at 50 per cent of the maximum. Dividing the sample into different redshift bins and comparing to the TFRs of a sample of local (z = 0) star-forming galaxies from the literature, we find no significant evolution in the slopes and zero-points of the TFRs since z ≈ 0.3, this in either luminosity or mass. In agreement with a growing number of CO TFR studies of nearby galaxies, we more generally find that CO is a suitable and attractive alternative to neutral hydrogen (HI). Our work thus provides an important benchmark for future higher redshift CO TFR studies

Population genomics of Bombus terrestris reveals high but unstructured genetic diversity in a potential glacial refugium

Ongoing climate change is expected to cause an increase in temperature and a reduction of precipitation levels in the Mediterranean region, which might cause changes in many species distributions. These effects negatively influence species gene pools, decreasing genetic variability and adaptive potential. Here, we use mitochondrial DNA and RADseq to analyse population genetic structure and genetic diversity of the bumblebee species Bombus terrestris (subspecies Bombus terrestris lusitanicus), in the Iberian Peninsula. Although this subspecies shows a panmictic pattern of population structure across Iberia and beyond, we found differentiation between subspecies B. t. lusitanicus and B. t. africanus, probably caused by the existence of barriers to gene flow between Iberia and North Africa. Furthermore, the results revealed that the Iberian Peninsula harbours a large fraction of B. terrestris intraspecific genetic variation, with the highest number of mitochondrial haplotypes found when compared with any other region in Europe studied so far, suggesting a potential role for the Iberian Peninsula as a glacial refugium. Our findings strengthen the idea that Iberia is a very important source of diversity for the global genetic pool of this species, because rare alleles might play a role in population resilience against human- or climate-mediated changes.info:eu-repo/semantics/publishedVersio

Compartmentalization of androgen receptors at endogenous genes in living cells

A wide range of nuclear proteins are involved in the spatio-temporal organization of the genome through diverse biological processes such as gene transcription and DNA replication. Upon stimulation by testosterone and translocation to the nucleus, multiple androgen receptors (ARs) accumulate in microscopically discernable foci which are irregularly distributed in the nucleus. Here, we investigated the formation and physical nature of these foci, by combining novel fluorescent labeling techniques to visualize a defined chromatin locus of AR-regulated genes-PTPRN2 or BANP-simultaneously with either AR foci or individual AR molecules. Quantitative colocalization analysis showed evidence of AR foci formation induced by R1881 at both PTPRN2 and BANP loci. Furthermore, single-particle tracking (SPT) revealed three distinct subdiffusive fractional Brownian motion (fBm) states: immobilized ARs were observed near the labeled genes likely as a consequence of DNA-binding, while the intermediate confined state showed a similar spatial behavior but with larger displacements, suggesting compartmentalization by liquid-liquid phase separation (LLPS), while freely mobile ARs were diffusing in the nuclear environment. All together, we show for the first time in living cells the presence of AR-regulated genes in AR foci.</p

Compartmentalization of androgen receptors at endogenous genes in living cells

A wide range of nuclear proteins are involved in the spatio-temporal organization of the genome through diverse biological processes such as gene transcription and DNA replication. Upon stimulation by testosterone and translocation to the nucleus, multiple androgen receptors (ARs) accumulate in microscopically discernable foci which are irregularly distributed in the nucleus. Here, we investigated the formation and physical nature of these foci, by combining novel fluorescent labeling techniques to visualize a defined chromatin locus of AR-regulated genes-PTPRN2 or BANP-simultaneously with either AR foci or individual AR molecules. Quantitative colocalization analysis showed evidence of AR foci formation induced by R1881 at both PTPRN2 and BANP loci. Furthermore, single-particle tracking (SPT) revealed three distinct subdiffusive fractional Brownian motion (fBm) states: immobilized ARs were observed near the labeled genes likely as a consequence of DNA-binding, while the intermediate confined state showed a similar spatial behavior but with larger displacements, suggesting compartmentalization by liquid-liquid phase separation (LLPS), while freely mobile ARs were diffusing in the nuclear environment. All together, we show for the first time in living cells the presence of AR-regulated genes in AR foci.</p

Compartmentalization of androgen receptors at endogenous genes in living cells

A wide range of nuclear proteins are involved in the spatio-temporal organization of the genome through diverse biological processes such as gene transcription and DNA replication. Upon stimulation by testosterone and translocation to the nucleus, multiple androgen receptors (ARs) accumulate in microscopically discernable foci which are irregularly distributed in the nucleus. Here, we investigated the formation and physical nature of these foci, by combining novel fluorescent labeling techniques to visualize a defined chromatin locus of AR-regulated genes-PTPRN2 or BANP-simultaneously with either AR foci or individual AR molecules. Quantitative colocalization analysis showed evidence of AR foci formation induced by R1881 at both PTPRN2 and BANP loci. Furthermore, single-particle tracking (SPT) revealed three distinct subdiffusive fractional Brownian motion (fBm) states: immobilized ARs were observed near the labeled genes likely as a consequence of DNA-binding, while the intermediate confined state showed a similar spatial behavior but with larger displacements, suggesting compartmentalization by liquid-liquid phase separation (LLPS), while freely mobile ARs were diffusing in the nuclear environment. All together, we show for the first time in living cells the presence of AR-regulated genes in AR foci.</p

PAXIP1 and STAG2 converge to maintain 3D genome architecture and facilitate promoter/enhancer contacts to enable stress hormone-dependent transcription

How steroid hormone receptors (SHRs) regulate transcriptional activity remains partly understood. Upon activation, SHRs bind the genome together with a co-regulator repertoire, crucial to induce gene expression. However, it remains unknown which components of the SHR-recruited co-regulator complex are essential to drive transcription following hormonal stimuli. Through a FACS-based genome-wide CRISPR screen, we functionally dissected the Glucocorticoid Receptor (GR) complex. We describe a functional cross-talk between PAXIP1 and the cohesin subunit STAG2, critical for regulation of gene expression by GR. Without altering the GR cistrome, PAXIP1 and STAG2 depletion alter the GR transcriptome, by impairing the recruitment of 3D-genome organization proteins to the GR complex. Importantly, we demonstrate that PAXIP1 is required for stability of cohesin on chromatin, its localization to GR-occupied sites, and maintenance of enhancer-promoter interactions. In lung cancer, where GR acts as tumor suppressor, PAXIP1/STAG2 loss enhances GR-mediated tumor suppressor activity by modifying local chromatin interactions. All together, we introduce PAXIP1 and STAG2 as novel co-regulators of GR, required to maintain 3D-genome architecture and drive the GR transcriptional programme following hormonal stimuli.</p

Targeting colorectal cancer stem cells with inducible caspase-9

Colorectal cancer stem cells (CSCs) drive tumor growth and are suggested to initiate distant metastases. Moreover, colon CSCs are reportedly more resistant to conventional chemotherapy, which is in part due to upregulation of anti-apoptotic Bcl-2 family members. To determine whether we could circumvent this apoptotic blockade, we made use of an inducible active caspase-9 (iCasp9) construct to target CSCs. Dimerization of iCasp9 with AP20187 in HCT116 colorectal cancer cells resulted in massive and rapid induction of apoptosis. In contrast to fluorouracil (5-FU)-induced apoptosis, iCasp9-induced apoptosis was independent of the mitochondrial pathway as evidenced by Bax/Bak double deficient HCT116 cells. Dimerizer treatment of colon CSCs transduced with iCasp9 (CSC-iCasp9) also rapidly induced high levels of apoptosis, while these cells were unresponsive to 5-FU in vitro. More importantly, injection of the dimerizer into mice that developed a colon CSC-iCasp9-induced tumor resulted in a strong decrease in tumor size, an increase in tumor cell apoptosis and a clear loss of CD133+ CSCs. Taken together, our data indicate that dimerization of iCasp9 circumvents the apoptosis block in CSCs, which results in effective tumor regression in vivo

Prognostic significance of N-Terminal Pro-BNP in patients with COVID-19 pneumonia without previous history of heart failure

Introduction:The objective of the present research was to evaluate the possible association between the N-terminal pro-brain type natriuretic peptide (NT-proBNP) levels and in-hospital mortality in coronavirus disease 2019 (COVID-19) pneumonia patients who did not have pre-existing heart failure (HF). Methods:A total of 137 consecutive patients without pre-existing HF and hospitalized due to COVID-19 pneumonia were enrolled into the current research. The main outcome of the research was the in-hospital death. The independent parameters linked with the in-hospital death were determined by multivariable analysis. Results: A total of 26 deaths with an in-hospital mortality rate of 18.9% was noted. Those who died were older with an increased frequency of co-morbidities such as hypertension, chronic kidney disease, coronary artery disease, stroke and dementia. They had also increased white blood cell (WBC) counts and had elevated glucose, creatinine, troponin I, and NT-pro-BNP levels but had decreased levels of hemoglobin. By multivariable analysis; age, NT-pro-BNP, WBC, troponin I, and creatinine levels were independently linked with the in-hospital mortality. After ROC evaluation, the ideal value of the NT-pro-BNP to predict the in-hospital mortality was found as 260 ng/L reflecting a sensitivity of 82% and a specificity of 93% (AUC:0.86; 95%CI:0.76-0.97). Conclusion: The current research clearly shows that the NT-proBNP levels are independently linked with the in-hospital mortality rates in subjects with COVID-19 pneumonia and without HF. Thus, we believe that this biomarker can be used as a valuable prognostic parameter in such cases