The atypical mammalian ligand Delta-like homologue 1 (Dlk1) can regulate Notch signalling in Drosophila

<p>Abstract</p> <p>Background</p> <p>Mammalian <it>Delta-like 1 </it>(<it>Dlk-1</it>) protein shares homology with Notch ligands but lacks a critical receptor-binding domain. Thus it is unclear whether it is able to interact with Notch <it>in vivo</it>. Unlike mammals, <it>Drosophila </it>have a single Notch receptor allowing a simple <it>in vivo </it>assay for mammalian <it>Dlk1 </it>function.</p> <p>Results</p> <p>Here we show that membrane-bound DLK1 can regulate Notch leading to altered cellular distribution of Notch itself and inhibiting expression of Notch target genes. The resulting adult phenotypes are indicative of reduced Notch function and are enhanced by <it>Notch </it>mutations, confirming that DLK1 action is antagonistic. In addition, cells expressing an alternative <it>Dlk1 </it>isoform exhibit alterations in cell size, functions previously not attributed to Notch suggesting that DLK1 might also act via an alternative target.</p> <p>Conclusion</p> <p>Our results demonstrate that DLK1 can regulate the Notch receptor despite its atypical structure.</p

Cellular apoptosis susceptibility (CSE1L/CAS) protein in cancer metastasis and chemotherapeutic drug-induced apoptosis

The cellular apoptosis susceptibility (CSE1L/CAS) protein is highly expressed in cancer, and its expression is positively correlated with high cancer stage, high cancer grade, and worse outcomes of patients. CSE1L (or CAS) regulates chemotherapeutic drug-induced cancer cell apoptosis and may play important roles in mediating the cytotoxicities of chemotherapeutic drugs against cancer cells in cancer chemotherapy. CSE1L was originally regarded as a proliferation-associated protein and was thought to regulate the proliferation of cancer cells in cancer progression. However, the results of experimental studies showed that enhanced CSE1L expression is unable to increase proliferation of cancer cells and CSE1L regulates invasion and metastasis but not proliferation of cancer cells. Recent studies revealed that CSE1L is a secretory protein, and there is a higher prevalence of secretory CSE1L in the sera of patients with metastatic cancer. Therefore, CSE1L may be a useful serological marker for screening, diagnosis and prognosis, assessment of therapeutic responses, and monitoring for recurrence of cancer. In this paper, we review the expression of CSE1L in cancer and discuss why CSE1L regulates the invasion and metastasis rather than the proliferation of cancer

HSP90 Inhibitors, Geldanamycin and Radicicol, Enhance Fisetin-Induced Cytotoxicity via Induction of Apoptosis in Human Colonic Cancer Cells

We revealed the cytotoxic effect of the flavonoid, fisetin (FIS), on human COLO205 colon cancer cells in the presence and absence of the HSP90 inhibitors, geldanamycin (GA) and radicicol (RAD). Compared to FIS treatment alone of COLO205 cells, GA and RAD significantly enhanced FIS-induced cytotoxicity, increased expression of cleaved caspase-3 and the PAPR protein, and produced a greater density of DNA ladder formation. GA and RAD also reduced the MMPs with induction of caspase-9 protein cleavage in FIS-treated COLO205 cells. Increased caspase-3 and -9 activities were detected in COLO205 cells treated with FIS+GA or FIS+RAD, and the intensity of DNA ladder formation induced by FIS+GA was reduced by adding the caspase-3 inhibitor, DEVD-FMK. A decrease in Bcl-2 but not Bcl-XL or Bax protein by FIS+GA or FIS+RAD was identified in COLO205 cells by Western blotting. A reduction in p53 protein with increased ubiquitin-tagged proteins was observed in COLO205 cells treated with FIS+GA or FIS+RAD. Furthermore, GA and RAD reduced the stability of the p53 protein in COLO205 cells under FIS stimulation. The evidence supports HSP90 inhibitors possibly sensitizing human colon cancer cells to FIS-induced apoptosis, and treating colon cancer by combining HSP90 inhibitors with FIS deserves further in vivo study

Automatic detection of the carotid artery boundary on cross-sectional MR image sequences using a circle model guided dynamic programming

Systematic aerobe training has positive effects on the compliance of dedicated arterial walls. The adaptations of the arterial structure and function are associated with the blood flow-induced changes of the wall shear stress which induced vascular remodelling via nitric oxide delivered from the endothelial cell. In order to assess functional changes of the common carotid artery over time in these processes, a precise measurement technique is necessary. Before this study, a reliable, precise, and quick method to perform this work is not present

Establishment of a Knock-In Mouse Model with the SLC26A4 c.919-2A>G Mutation and Characterization of Its Pathology

Recessive mutations in the SLC26A4 gene are a common cause of hereditary hearing impairment worldwide. Previous studies have demonstrated that different SLC26A4 mutations may have different pathogenetic mechanisms. In the present study, we established a knock-in mouse model (i.e., Slc26a4tm1Dontuh/tm1Dontuh mice) homozygous for the c.919-2A>G mutation, which is a common mutation in East Asians. Mice were then subjected to audiologic assessment, a battery of vestibular evaluations, and inner ear morphological studies. All Slc26a4tm1Dontuh/tm1Dontuh mice revealed profound hearing loss, whereas 46% mice demonstrated pronounced head tilting and circling behaviors. There was a significant difference in the vestibular performance between wild-type and Slc26a4tm1Dontuh/tm1Dontuh mice, especially those exhibiting circling behavior. Inner ear morphological examination of Slc26a4tm1Dontuh/tm1Dontuh mice revealed an enlarged endolymphatic duct, vestibular aqueduct and sac, atrophy of stria vascularis, deformity of otoconia in the vestibular organs, consistent degeneration of cochlear hair cells, and variable degeneration of vestibular hair cells. Audiologic and inner ear morphological features of Slc26a4tm1Dontuh/tm1Dontuh mice were reminiscent of those observed in humans. These features were also similar to those previously reported in both knock-out Slc26a4−/− mice and Slc26a4loop/loop mice with the Slc26a4 p.S408F mutation, albeit the severity of vestibular hair cell degeneration appeared different among the three mouse strains

ALMA Survey of Orion Planck Galactic Cold Clumps (ALMASOP) : How Do Dense Core Properties Affect the Multiplicity of Protostars?

During the transition phase from a prestellar to a protostellar cloud core, one or several protostars can form within a single gas core. The detailed physical processes of this transition, however, remain unclear. We present 1.3 mm dust continuum and molecular line observations with the Atacama Large Millimeter/submillimeter Array toward 43 protostellar cores in the Orion molecular cloud complex (lambda Orionis, Orion B, and Orion A) with an angular resolution of similar to 0.'' 35 (similar to 140 au). In total, we detect 13 binary/multiple systems. We derive an overall multiplicity frequency (MF) of 28% +/- 4% and a companion star fraction (CSF) of 51% +/- 6%, over a separation range of 300-8900 au. The median separation of companions is about 2100 au. The occurrence of stellar multiplicity may depend on the physical characteristics of the dense cores. Notably, those containing binary/multiple systems tend to show a higher gas density and Mach number than cores forming single stars. The integral-shaped filament of the Orion A giant molecular cloud (GMC), which has the highest gas density and hosts high-mass star formation in its central region (the Orion Nebula cluster), shows the highest MF and CSF among the Orion GMCs. In contrast, the lambda Orionis GMC has a lower MF and CSF than the Orion B and Orion A GMCs, indicating that feedback from H ii regions may suppress the formation of multiple systems. We also find that the protostars comprising a binary/multiple system are usually at different evolutionary stages.Peer reviewe

ATOMS : ALMA Three-millimeter Observations of Massive Star-forming regions - I. Survey description and a first look at G9.62+0.19

The ATOMS, standing for ALMA Three-millimeter Observations of Massive Star-forming regions, survey has observed 146 active star-forming regions with ALMA band 3, aiming to systematically investigate the spatial distribution of various dense gas tracers in a large sample of Galactic massive clumps, to study the roles of stellar feedback in star formation, and to characterize filamentary structures inside massive clumps. In this work, the observations, data analysis, and example science of the ATOMS survey are presented, using a case study for the G9.62+0.19 complex. Toward this source, some transitions, commonly assumed to trace dense gas, including CS J = 2-1, HCO+ J = 1-0, and HCN J = 1-0, are found to show extended gas emission in low-density regions within the clump; less than 25 per cent of their emission is from dense cores. SO, CH3OH, (HCN)-C-13, and HC3N show similar morphologies in their spatial distributions and reveal well the dense cores. Widespread narrow SiO emission is present (over similar to 1 pc), which may be caused by slow shocks from large-scale colliding flows or HII regions. Stellar feedback from an expanding HII region has greatly reshaped the natal clump, significantly changed the spatial distribution of gas, and may also account for the sequential high-mass star formation in the G9.62+0.19 complex. The ATOMS survey data can be jointly analysed with other survey data, e.g. MALT90, Orion B, EMPIRE, ALMA IMF, and ALMAGAL, to deepen our understandings of 'dense gas' star formation scaling relations and massive protocluster formation.Peer reviewe

ATOMS : ALMA three-millimeter observations of massive star-forming regions - II. Compact objects in ACA observations and star formation scaling relations

We report studies of the relationships between the total bolometric luminosity (L-bol or L-TIR) and the molecular line luminosities of J = 1 - 0 transitions of (HCN)-C-13, (HCO+)-C-13, HCN, and HCO+ with data obtained from ACA observations in the 'ATOMS' survey of 146 active Galactic star-forming regions. The correlations between L-bol and molecular line luminosities L-mol' of the four transitions all appear to be approximately linear. Line emission of isotopologues shows as large scatters in L-bol-L-mol' relations as their main line emission. The log(L-bol/L-mol') for different molecular line tracers have similar distributions. The L-bol-to-L-mol' ratios do not change with galactocentric distances (R-GC) and clump masses (M-clump). The molecular line luminosity ratios (HCN-to-HCO+, (HCN)-C-13-to-(HCO+)-C-13, HCN-to-(HCN)-C-13, and HCO+-to-(HCO+)-C-13) all appear constant against L-bol, dust temperature (T-d), M-clump, and R-GC. Our studies suggest that both the main lines and isotopologue lines are good tracers of the total masses of dense gas in Galactic molecular clumps. The large optical depths of main lines do not affect the interpretation of the slopes in star formation relations. We find that the mean star formation efficiency (SFE) of massive Galactic clumps in the 'ATOMS' survey is reasonably consistent with other measures of the SFE for dense gas, even those using very different tracers or examining very different spatial scales.Peer reviewe

ATOMS : ALMA three-millimeter observations of massive star-forming regions - III. Catalogues of candidate hot molecular cores and hyper/ultra compact H II regions

A correction has been published: Monthly Notices of the Royal Astronomical Society, Volume 511, Issue 1, March 2022, Pages 501–505, https://doi.org/10.1093/mnras/stac039We have identified 453 compact dense cores in 3mm continuum emission maps in the ALMA Three-millimetre Observations of Massive Star-forming regions survey, and compiled three catalogues of high-mass star-forming cores. One catalogue, referred to as hyper/ultra compact (H/UC)-HII catalogue, includes 89 cores that enshroud H/UC HII regions as characterized by associated compact H40 alpha emission. A second catalogue, referred to as pure s-cHMC, includes 32 candidate hot molecular cores (HMCs) showing rich spectra (N >= 20 lines) of complex organic molecules (COMs) and not associated with H/UC-HII regions. The third catalogue, referred to as pure w-cHMC, includes 58 candidate HMCs with relatively low levels of COM richness and not associated with H/UC-Hii regions. These three catalogues of dense cores provide an important foundation for future studies of the early stages of high-mass star formation across the Milky Way. We also find that nearly half of H/UC-HII cores are candidate HMCs. From the number counts of COM-containing and H/UC-HII cores, we suggest that the duration of high-mass protostellar cores showing chemically rich features is at least comparable to the lifetime of H/UC-HII regions. For cores in the H/UC-HII catalogue, the width of the H40 alpha line increases as the core size decreases, suggesting that the non-thermal dynamical and/or pressure line-broadening mechanisms dominate on the smaller scales of the H/UC-HII cores.Peer reviewe

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat